Claude Universite

Bernard -Lyon

M François-Noël

Gilly M Le Professeur

Hamda Ben

Hadid M Le Professeur

Philippe Lalle

M Le Professeur

Germain Gillet

M Alain Helleu

Keywords: Tabac, Cancer, Immigrés, France, Danemark, Etude pilote Tobacco, Smoking, Cancer, Immigrants, France, Denmark, Pilot study

Résumé en Français

Les migrations internationales augmentent et l'Europe ne fait pas exception avec plus de 10% de la population de l'Union Européenne en 2014. Une question importante est le tabagisme des immigrés qui pourrait entraîner des risques de maladies liées au tabac différents de ceux des natifs des pays hôtes. Pourtant, on ne connait que très peu l'usage du tabac, qui est une cause évitable de cancer, et les maladies liées au tabac chez les immigrés en Europe.

L'objectif général de cette thèse était d'étudier l'usage du tabac et le risque de cancers liés au tabac chez les immigrés. Les objectifs spécifiques étaient de:

• enquêter sur le tabagisme et ses déterminants chez les immigrés en France (étude pilote TOBAMIG),

• comparer l'incidence des cancers liés au tabac entre les immigrés et les natifs au Danemark,

• mettre ces résultats en contexte avec les connaissances actuelles, et • suggérer un design d'étude sur le tabagisme et le risque de cancer lié chez les immigrés en France. L'étude pilote TOBAMIG a collecté des informations sur l'usage du tabac dans un échantillon d'immigrés, représentatif pour la plupart des caractéristiques démographiques. Avec des modifications, les résultats indiquent la faisabilité d'une étude à grande échelle en France. Au Danemark, le taux d'incidence des cancers liés au tabac chez les immigrés était inférieur à celui des natifs ; cependant, de grandes disparités ont été observées par site cancéreux et pays d'origine, suggérant en outre un rôle du tabagisme dans les pays d'origine des immigrés. Enfin, deux designs d'étude sont proposés, qui varient en fonction de la quantité d'information recherchée, afin de mieux comprendre le tabagisme des immigrés.

Acknowledgement

I would like to thank my thesis director Anne-Marie SCHOTT, my thesis co-director Joachim SCHUZ and my supervisor Maria LEON ROUX for giving me the chance to do my PhD at the International Agency for Research on Cancer. In particular, I would like to thanks them for the trust they showed me during these 4 years. I would also like to acknowledge the financial support I received from the French "Ligue Nationale Contre le Cancer" who granted me a 3-years doctoral grant and the International Agency for Research on Cancer who supported me when the former grant ended, for an additional 15 months. I wish to thank the people who have given their time to take part in the TOBAMIG survey.

I am also grateful to my colleagues at IARC who have been supportive and have given precious advice at different times during the preparation of this thesis. Furthermore, I want to thank the colleagues who helped proof-read my thesis.

I would like to acknowledge Susanne DALTON, Pierre CHAUVIN and Edouard TURSAN

Reśumé substantiel en français

Introduction

Les migrations internationales augmentent et l'Europe ne fait pas exception à ce phénomène. En 2014, Les immigrés représentaient plus de 10% de la population dans l'Union Européenne. Une question importante est la santé des immigrés, étant donné que les immigrés peuvent avoir des comportements différents en matière de santé.

Par exemple, ils peuvent consommer le tabac différemment, tant en intensité de consommation que de produits utilisés (cigarette, chicha, tabac sans fumée), ce qui pourrait entraîner des risques différents de maladies attribuables au tabac par rapport aux natifs des pays d'accueil. Pourtant, on ne connait que très peu l'usage du tabac et le fardeau des maladies liées au tabac chez les immigrés en Europe. C'est une question importante puisque l'usage du tabac est une cause évitable majeure de cancer, et est maintenant un facteur de risque établi pour environ 20 types de cancer.

En Europe, on estime qu'environ un cas de cancer sur cinq est causé par la cigarette.

Par conséquent, l'étude de l'usage du tabac et des cancers liés au tabac chez les immigrés est d'une importance grandissante.

Nous nous attendons à ce que les normes et les traditions des pays d'origine continuent d'influencer le comportement des migrants après leur installation dans les pays d'accueil Européens. Par conséquent, nous prévoyons que la prévalence du tabagisme -incluant les cigarettes, les cigares et les narguilés, ainsi que l'utilisation de tabac sans fumée à priser et à chiquer -chez les migrants montre une tendance similaire à la prévalence dans les pays d'origine. Plus précisément, les migrants originaires d'un pays avec une prévalence du tabagisme particulièrement faible consommeraient moins de tabac que les migrants venant de pays à forte prévalence du tabagisme, ou que les natifs des pays hôte Européens à forte prévalence du tabagisme.

Nous nous attendons également à ce que l'acculturation modifie les comportements spécifiques des populations migrantes. Il a été observé que les migrants de la deuxième génération ou ceux qui ont émigré à un jeune âge ou résidé pendant une longue période dans le pays hôte sont plus semblable à la population d'accueil dans leur usage du tabac que ceux qui ont émigré plus tard dans la vie ou ont résidé une période plus courte dans le pays hôte. Ceci est d'une importance particulière compte tenu de la différence de prévalence du tabagisme entre les hommes et les femmes qui est encore très importante dans les pays en développement, tandis que dans les pays développés, comme les pays européens, cette différence s'est atténuée dans une large mesure.

Objectifs

L'objectif général de cette thèse était d'étudier l'usage du tabac et le risque de cancers liés au tabac chez les immigrés en développant un protocole de collecte et d'analyse des informations pertinentes. Les quatre objectifs spécifiques de la thèse étaient:

• d'enquêter sur l'usage du tabac et les déterminants de son utilisation chez les immigrés en France en testant un protocole d'étude et un questionnaire pour la collecte des données dans une étude pilote (TOBAMIG),

• de comparer l'incidence des cancers liés au tabac entre les immigrés et les natifs au Danemark,

• de mettre ces résultats en contexte avec les connaissances actuelles sur l'usage du tabac et de l'incidence et de la mortalité des cancers liés au tabac dans les populations immigrées en Europe, et

Méthodes

En vue de faire le point sur les connaissances sur l'usage du tabac et le fardeau des cancers liés au tabac chez les immigrés en France, deux revues de la littérature ont été effectuées sur ce qui a été publié dans ce domaine en Europe. Par conséquent, une recherche a été effectuée à l'aide de la base de données PubMed et d'une combinaison de mots-clés et de terme MeSH. Toutes les études originales, soumises à un comité de lecture international, en langue française ou anglaise, publiées après 1990 ont été inclues. L'étude de faisabilité TOBAMIG s'est concentrée sur les immigrés adultes noneuropéens de 1 ère et 2 ème génération, dans les 6 communes ayant la plus grande proportion d'immigrés de la région lyonnaise. Les données ont été recueillies anonymement en entretiens en face à face, pendant 2 mois en 2013. Une combinaison de 8 types de lieux a été choisie pour recruter un échantillon représentatif de la population cible.

Pour l'étude de cohorte au Danemark, nous avons utilisé une cohorte existante de l'ensemble des hommes vivant au Danemark entre 1978 et 2010, établie initialement pour l'étude du cancer du testicule. Nous avons calculé les ratios standardisés d'incidence (SIR) avec des intervalles de confiance à 95%, pour comparer l'incidence par statut migratoire et par pays de naissance pour 9 sites de cancers liés au tabac : poumon, larynx, vessie, oropharynx, oesophage, cavité buccale, foie, estomac et pancréas. Pour les cancers du poumon, nous avons étudié l'incidence par sous-types histologiques.

Résultats

Le premier enseignement à travers les deux revues de la littérature sur l'usage du tabac et sur le fardeau des cancers lié au tabac chez les immigrés en Europe est que, malgré une augmentation de la population de ce groupe minoritaire dans les pays d'accueil européens, on connait peu le statut et les évolutions en matière de santé et de mode de vie des immigrés, qui contribuent à leur risque de cancer. L'étude d'un sous-groupe démographique qui représente une faible proportion de la population d'un pays constitue un défi que les chercheurs de plusieurs pays ont abordé différemment, dans une large mesure en fonction des ressources disponibles dans ces pays. Dans la 1 ère revue de la littérature, nous avons observé les méthodes d'échantillonnage utilisées pour identifier et recruter des immigrants dans les études épidémiologiques sur l'usage du tabac. Les protocoles d'étude basés sur des registres, où les immigré et les natifs peuvent être identifiés, offraient une approche directe pour atteindre la population cible et s'assurer de la représentativité, avec des données collectées en routine et une grande taille d'échantillon.

Les résultats ont montré que l'étude pilote TOBAMIG a collecté avec succès des informations sur l'usage du tabac et les déterminants de son utilisation dans un échantillon d'immigrés. Lors de la phase d'enquête de terrain, 84 personnes ont été interrogées, dont 75 participants éligibles (49 immigrés de 1 ère génération et 26 de 2 ème génération). La prévalence tabagique était supérieure à celle de la population générale française. Notre échantillon était similaire pour la plupart des caractéristiques démographiques à la population immigrée du lieu d'échantillonnage.

Les principaux pays d'origine étaient l'Algérie (29%), la Tunisie (21%), le Maroc (9%), et la Turquie (7%). Notre étude a également montré que les sites à forte circulation piétonne ont donné une meilleure participation. Bien que les résultats indiquent la faisabilité d'une étude à grande échelle sur l'usage du tabac et de ses déterminants en France, plusieurs limites sont apparues, qui peuvent conditionner la mise en oeuvre d'une étude plus vaste.

Au Danemark, nous avons identifié 131 317 cas de cancers d'intérêt parmi 3 508 204 hommes (dont 280 526 immigrés de 1 ère génération et 129 056 de 2 nde génération). Le taux global d'incidence des 9 principaux cancers liés au tabac chez les immigrés des 22 générations était inférieur de 15% à celui des natifs. Cependant, de grandes disparités ont été observées par site cancéreux et pays d'origine. Par rapport aux natifs Danois, l'incidence du cancer du poumon chez les immigrés de 1 ère et 2 ème génération était inférieure de 10% et 27% respectivement. Cependant, l'incidence du cancer du poumon chez les immigrés de 1 ère génération a augmenté pour rejoindre le niveau d'incidence des natifs vers la fin des années 2000. Les immigrés de 1 ère génération ont montré une incidence du cancer de la vessie d'environ 50% inférieure à celle des natifs. Toutefois, les ratios standardisés d'incidence étaient élevés chez les immigrés pour les cancers du foie et de l'estomac.

Discussion

Dans le contexte français où des registres de population incluant des informations sur le pays de naissance ne sont pas disponibles, nous avons élaboré un protocole de recherche novateur. Notre méthode est similaire par certains aspects à d'autres études existantes, par exemple l'utilisation d'enquêteurs formés appartenant au groupe cible des immigrés à échantillonner, postés dans des lieux publics connus pour être fréquentés par la population immigrée. Mais notre approche d'échantillonnage est unique par son échantillonnage dans un ensemble de sites connus pour être fréquenté par les immigrés, situés dans des communes à forte proportion d'immigrés, et sélectionnés afin de capturer les profils démographiques différents pour assurer un échantillon le plus proche possible de la population immigrée de ces municipalités.

Dans l'étude de faisabilité TOBAMIG, la durée des entretiens s'est révélée inadaptée pour les paramètres de ce type d'enquête effectuée lors de visites fortuites dans des lieux publics; en particulier, l'anonymat ne permet pas le suivi des réponses manquantes. Par ailleurs, les lieux les plus fréquentés ont démontrés la possibilité de fournir l'anonymat nécessaire pour administrer le questionnaire.

Les données de l'étude de cohorte au Danemark suggèrent que les habitudes de tabagisme des pays d'origine de l'immigré ont un rôle primordial dans les cancers liés au tabac, mais cela doit être confirmé en utilisant des données individuelles de statut tabagique.

Enfin, deux designs d'étude pour des études futures à grande échelle sont proposés afin de mieux comprendre la santé des immigrés et de leur usage du tabac. Les deux options varient en fonction de la quantité d'information recherchée : 1) un petit ensemble d'informations (par exemple, la prévalence de consommation des produits du tabac) peut être recueilli rapidement à travers une enquête de terrain en face-àface dans une combinaison de zones géographiques et de types de lieux ou, 2) un ensemble complet d'informations dans un échantillon représentatif d'immigrant, avec possibilité d'inclure les natifs peuvent être collectées via des enquêtes téléphoniques non anonymes.

Conclusion

Le paysage des populations européennes change en devenant une société de plus en plus multiculturelle et multiethnique. Par conséquence, la santé des immigrés représente un défi de santé publique pour garantir le plus haut niveau possible de santé pour tout individu, l'équité et l'accès aux soins de santé. En outre, d'un point de vue épidémiologique, la recherche sur la santé des immigrés a encore un long chemin à faire pour obtenir des informations complètes, y compris sur leur consommation de tabac et la morbidité et mortalité associées au tabac.

Nos résultats de TOBAMIG démontrent la faisabilité d'une étude à grande échelle sur le tabagisme des populations immigrées en France. Les modifications principales à apporter au protocole seraient l'inclusion des natifs, une concentration du recrutement sur des lieux à forte fréquentation et la réduction de la durée de l'entretien.

Les résultats de l'étude Danoise ont mis en évidence une incidence des cancers liés au tabac inférieure chez les immigrés par rapport aux natifs. L'incidence inférieure des cancers de la vessie chez les immigrés de 1 ère génération nécessite davantage de recherche.

À l'issue de cette thèse, une chose apparaît comme évidente: autant il est imprécis d'analyser l'état de santé des individus sans faire la distinction entre les hommes et les femmes ou sans tenir compte de l'environnement social, autant il est inexact d'étudier la santé des immigrés indépendamment de leur diversité en termes d'origines géographiques, de durée de séjour dans le pays d'accueil ainsi que de leurs conditions de vie. Nos résultats confirment les conclusions précédemment établies dans la littérature, comme l'incidence et la mortalité globalement inférieure des cancers liés au tabac chez les immigrés par rapport aux natifs, mais avec de grandes disparités par cancer lié au tabac selon le pays de naissance et le sexe des immigrés.

Enfin, même si la littérature actuelle est rare par rapport à la taille de plus en plus importante des populations immigrées en Europe, il est déjà établi comme nécessaire d'agir sur la santé des immigrés. De manière à atteindre cet objectif, les politiques et les interventions de santé publique prenant en compte les comportements de santé des immigrés sont cruciales.

Table of content

OVERVIEW

The overall objective of the thesis was to investigate tobacco use and tobacco-related cancer (TRC) risks in immigrants in France. All the cancers that are caused by tobacco use, in all its forms, are referred to as TRC.

One original specific objective of this thesis was to describe the tobacco use in a To investigate TRC risk in migrants we searched for any existing data sources in France, and then later expanded the search to the rest of Europe. We successfully identified cancer incidence data from a cohort comprising the whole Danish male population. This dataset included information allowing to compare the incidence of selected TRC between native Danes and migrants (1 st and 2 nd generations). This study allowed us to appropriately address this complementing research question. In summary, designing, collecting and analysing data on tobacco use and TRC in immigrants constitute the central themes of this dissertation.

The terms and definitions used in the field of migration research are numerous as there is no universally accepted definition for "migrant". The different definitions mainly vary depending on the specificity of the term but also on the context in which they are used. A migrant is the broader term used for a person who, according to the International Organization for Migration (IOM, http://www.iom.int/), moves to another country or region to better their material or social conditions and improve the prospect for themselves or their family. Therefore, the term "migrants" include many different situations such as economic migrants, refugees, undocumented migrants as well as intra-national migrants (e.g. ruralurban migrants). An immigrant is a non-national who moves into a country for the purpose of settlement. In this thesis, the term "migrant" is used in a broad manner to cover all type of migration into a country differing from one's country of birth. The term "immigrant" is used from the perspective of the host-country, i.e. France or Denmark.

Although the descendants of immigrants -referred to as 2 nd generation immigrants as opposed to their parents referred to as 1 st generation immigrants -did not actively migrated themselves, they often share similar conditions, i.e. in life-style behaviours, that are related to the migration, cultural and geographical origin of their parents. In this regard, the use of the term "2 nd generation immigrant" appears to be inappropriate. However, as this term is widely used in the scientific literature to designate the descendants of one or two 1 st generation immigrants, it was decided in this thesis to stick to this conventional terminology.

In a country, most of the time, the immigrant population is constituted gradually, and the proportion of immigrants at any point in time reflects past immigration flows. The population of immigrants residing today in the host country results from successive waves of immigration, less losses in number of immigrants incurred due to departures or deaths.

When used as part of a research study, it is often believed that once an analysis is adjusted for social class-often measured by individual socio-economic position -migration or ethnic inequalities in health disappear or are considerably reduced. Nevertheless, conflating migration status and social class fail to disentangle differences by country of birth and socioeconomic position, which could highlight health inequalities [START_REF] Lorant | Ethnicity, socio-economic status and health research: insights from and implications of Charles Tilly's theory of Durable Inequality[END_REF]. In addition to isolating the determinants of migrants' health of interest to a study, it is important to clarify the scope within which migrant health is to be assessed. The scope refers to consideration of the complete migration process not only from a receiving country perspective but within all stages: pre-departure, migration journeys, destination, and return to sending countries. The "healthy migrant effect", is one of the concepts that was proposed to explain the migration of healthier people which is associated with positive health outcomes in comparison to their counterparts in the home country but can deteriorate over time as migrants adopt risky health behaviours (e.g. smoking patterns) specific of host country populations (referred to as acculturation). These changing health patterns in immigrants have been associated with a high prevalence of non-communicable diseases, among some 1 st and 2 nd generation migrant groups [START_REF] Kennedy | The healthy immigrant effect and immigrant selection: Evidence from four countries[END_REF] Although France has a long history of migration, studies on behaviours impacting the health of migrants are few. The scarcity of studies may be related to the complexity of either accessing the target population or developing appropriate study protocols for these population groups [START_REF] Parkin | Studies of cancer in migrants: rationale and methodology[END_REF]. Additionally, ideological or political motives may be a barrier due to concerns that data on health-related behaviours and the corresponding morbidity and mortality could be used to the disadvantage of immigrants. Additionally, as mentioned previously, it is often believed that differences in health outcomes between immigrants and natives are mainly attributable to socioeconomic differences. In France, migrant health emerged as a research field in the 1990s, with pioneer studies on mortality (Khlat, 1995, Courbage andKhlat, 1996) and morbidity [START_REF] Khlat | La morbidité dans les ménages originaires du Maghreb, sur la base de l'enquête Santé de l'Insee, 1991-1992[END_REF][START_REF] Mizrahi | Accès aux soins et état de santé des populations immigrées[END_REF]. In the 2000s, migrant status was added to the general population health survey, allowing for a better description of migrant health. However, the conclusions that could be drawn from these data were limited as the number of migrants was too low in general population surveys to allow a description of the results by country of origin or length of stay.

From 2008, the "Trajectories and Origin" (TeO) survey [START_REF] Beauchemin | Trajectories and Origins[END_REF] in France focused on the issues of immigration: integration and discrimination -which are major national topics of public debate -aimed to identify the impact of origins on living conditions and social trajectories. Questions on health were included but did not cover tobacco use, despite tobacco use being a major determinant of health and health inequalities.

Literature search strategy on tobacco use in immigrants

In order to inform the original focus of this thesis on tobacco use in immigrants in France, a literature review was conducted to identify the published research addressing tobacco use in migrants in Europe. Although it is an important component of the study and an ongoing review of the literature was conducted from the outset, the completion of the systematic search was delayed to permit analysis of the Danish database and preparation of the first publication contributing to this dissertation. Accordingly, I designed a search in August 2015 using PubMed with a combination of MeSH terms and keywords as displayed in Figure 1.1.

The 519 papers retrieved were filtered first on title (210 articles remained) and then by abstract (48 articles remained) following the inclusion and exclusion criteria listed below.

Finally, the full-texts of the remaining articles were assessed and 33 articles were retained in the review.

Synthesis of results

The results reported in the selected articles (n=33) were included in this review regardless of their statistical significance. I did not perform a meta-analysis as populations of interest, definitions and measurements of variables were not consistent across the studies to combine them in a quantitative way. Iranian immigrant smoking patterns in Sweden was investigated in one study [START_REF] Koochek | Is migration to Sweden associated with increased prevalence of risk factors for cardiovascular disease?[END_REF]. A higher smoking rate was observed in Iranian men and women residing in Sweden. In

France, Wanner at al. observed a higher likelihood of smoking in North African immigrant men compared to the natives (OR=1.37, p<0.05) as well as a higher intensity of smoking (Wanner et al., 1995b). On the contrary, North African immigrant women were less likely to be current smokers than French native women (Wanner et al., 1995b).

Four studies (Ezika, were also observed between host-country, according to their general population smoking prevalence. In the population aged 50 years and older of 11 European countries, the overall smoking behaviour was similar between immigrants and the native-born population in 2004-2005 (Sole-Auro and Crimmins, 2008). Still, diverging trends were observed by country of origin: in most of the studies, Turkish immigrants had a higher smoking than the natives of their host-country, while South Asian immigrants -and especially South Asian immigrant women -had a lower smoking prevalence than their host-countries' native counterparts.

Sampling methods

In The strength of these studies is their large sample sizes -more than 770,000 in Aspinall et al.

study -which enable to differentiate between a wider range of immigrant groups. Another recruitment avenue employed in the studies reviewed is via health centres. In a suburb of Stockholm, Swedes and immigrants were recruited when they attended health centres for a health check, allowing also for biological investigations relating to tobacco use [START_REF] Tomson | Risk factors for cardiovascular disease--a comparison between Swedes and immigrants[END_REF]. In Sweden, invitation to participate in a study on migration and cardiovascular disease, including exposure to smoking, was conducted via a letter distributed to all Iranianborn persons in the township of Kista, Greater Stockholm [START_REF] Koochek | Is migration to Sweden associated with increased prevalence of risk factors for cardiovascular disease?[END_REF]. This type of approach is only possible where a population registry exists and distinction of residents according to immigration status is not sanctioned by laws or ethical confidentiality concerns.

In contrast, in the United Kingdom and Ireland, exploration of smoking in migrants was performed by invitation through the use of flyers, posters, word of mouth and advertisement in local migrant community magazine, and responders completed an interviewer-administered questionnaire [START_REF] Ezika | An exploration of smoking behavior of african male immigrants living in glasgow[END_REF][START_REF] Kabir | Smoking characteristics of Polish immigrants in Dublin[END_REF]. Interviewers were also recruited from the target migrant group. They were trained before being posted at busy intersection of the city area and in the neighbourhoods of numerous target migrant group shops [START_REF] Kabir | Smoking characteristics of Polish immigrants in Dublin[END_REF]. Despite smaller samples, this recruitment method illustrated the potential to collect qualitative information in immigrants in the absence of a populationbased register. However, this method has limitations in terms of representativeness of its sample as it consists of a convenient sample with similar age and sex distributions in immigrants and natives. In the absence of active measures preventing potential selection bias in the sampling protocol, this approach may attract health-conscious individuals who self-select themselves.

From the 1 st literature review we identified the sampling methodologies used to identify and recruit immigrants in epidemiologic studies investigating tobacco use. Registry-based study protocols where immigrants and natives can be identified offered a straight forward approach to reach the target population and ensure representativeness, as data are collected in routine and the sample sizes are large. Often due to the lack of such registries in the countries where studies on immigrants have been conducted, identification through household or public place surveys was a commonly used sampling method.

Tobacco-related cancers in migrants in Europe

Studies on cancer in immigrants to the USA have shown that the incidence of some common cancers changed to the level of the new host country within 1 or 2 generations [START_REF] Parkin | Studies of cancer in migrants: rationale and methodology[END_REF]. For instance, stomach cancer incidence rates in Japanese immigrants to Hawaii were lower than in Japan, and in Hawaii-born Japanese they were even lower but remained higher than in the white population [START_REF] Hanai | Cancer incidence in Japan in 1975 and changes of epidemiological features for cancer in Osaka[END_REF]. These findings were influential to the understanding of the environmental aetiology of human cancer [START_REF] Hemminki | The balance between heritable and environmental aetiology of human disease[END_REF]. The continuation of previously recorded rates across various generations of immigrants illustrated the role of genetic susceptibility in determining cancer risk, while a rapid change in rates following immigration implies that lifestyle or environment are more influential modifiers of cancer outcomes [START_REF] Parkin | Studies of cancer in migrants: rationale and methodology[END_REF].

In in the study (e.g. for adjustment purpose). One study was excluded as it was retracted by its authors.

Figure 1.2: Inclusion and exclusion of publications in the systematic review on tobacco related cancers in migrants in Europe.

Synthesis of results

Sixty articles were included in this review. The studies included were conducted in 9 countries: Belgium, Denmark, France, Germany, the Netherlands, Spain, Switzerland, Sweden and the United Kingdom. However, a majority (n=34) of the studies were conducted in the United Kingdom or Sweden. The 60 articles were published between 1993 and 2014 and referred to data collected on the period from 1958 to 2009. None of the studies investigated individual tobacco use status. The studies investigated either incidence or mortality of TRCs, with only 2 studies looked at TRC survival in immigrants [START_REF] Nilsson | Cancer survival in Estonian migrants to Sweden[END_REF][START_REF] Siemerink | Survival of non-Western first generations immigrants with stomach cancer in North East Netherlands[END_REF]. In these 2 studies, looking at Estonian immigrants in Sweden and first generation immigrants in the Netherlands, it was shown that a better survival for lung or stomach cancers in immigrants than in the natives of the respective host-countries.

All results are given in comparison with the respective host-countries' natives. Only the statistically significant trends are presented, unless otherwise specified.

Turkish immigrants

As Turkey is a country with one of the highest number of immigrants to any European country, ten studies investigated the incidence or mortality by cancer in Turkish immigrants.

In Belgium, Denmark, France, Germany, the Netherlands and Sweden, Turkish immigrants Wales [START_REF] Haworth | Cirrhosis and primary liver cancer amongst first generation migrants in England and Wales[END_REF], and in immigrants from Ethiopia, Ghana and Somalia in the Netherlands. For lung cancer the differences were more obvious by sex. In England and

had
Wales lower mortality of lung cancer was observed in West African and East African men than in nationals [START_REF] Grulich | Cancer mortality in African and Caribbean migrants to England and Wales[END_REF], which was also the case for Southeast African immigrant men in Sweden [START_REF] Mousavi | Esophageal cancer risk among immigrants in Sweden[END_REF]. However, in Southeast African immigrant women to Sweden there was a higher incidence of lung cancer compared to the natives [START_REF] Mousavi | Esophageal cancer risk among immigrants in Sweden[END_REF]. Stomach cancer mortality was also lower for immigrant men from East African countries in England [START_REF] Grulich | Cancer mortality in African and Caribbean migrants to England and Wales[END_REF]. On the other hand, the mortality rates of other TRCs were elevated. Notably, higher bladder cancer mortality in Algerian immigrants in France [START_REF] Bouchardy | Cancer mortality among north African migrants in France[END_REF]

European and other origin immigrants

Twenty eight studies investigated the overall cancer and TRC burden in immigrants born in a

European country, who have immigrated to another European country, as intra-European

Union migration has been an important phenomenon for decades. In particular, five studies focused solely on Italian immigrant in different countries [START_REF] Swerdlow | Cancer in Italian migrant populations. England and Wales: incidence[END_REF][START_REF] Head | Cancer in Italian migrant populations. England and Wales: mortality[END_REF][START_REF] Black | Cancer in Italian migrant populations[END_REF][START_REF] Sarti | Cancer in Italian migrant populations[END_REF][START_REF] Bouchardy | Cancer in Italian migrant populations[END_REF]. The overall cancer mortality in Italian immigrant men and women was shown to be lower in the United Kingdom, compared to the natives [START_REF] Black | Cancer in Italian migrant populations[END_REF][START_REF] Head | Cancer in Italian migrant populations. England and Wales: mortality[END_REF]. Whereas, in France Italian immigrant women had lower overall cancer mortality but men had higher mortality [START_REF] Bouchardy | Cancer in Italian migrant populations[END_REF]. Four other studies investigated the cancer mortality and incidence in immigrants from the Former Soviet Union in Germany [START_REF] Winkler | Cancer incidence in ethnic German migrants from the Former Soviet Union in comparison to the host population[END_REF], Winkler et al., 2009[START_REF] Kyobutungi | Mortality from cancer among ethnic German immigrants from the Former Soviet Union, in Germany[END_REF][START_REF] Ronellenfitsch | Stomach cancer mortality in two large cohorts of migrants from the Former Soviet Union to Israel and Germany: are there implications for prevention?[END_REF]. These studies found mostly non-significant differences in the cancer mortality or incidence compared to the German natives, with the exception of a lower all-cancer mortality in women from the Former Soviet Union (SIR 0.95, p<0.05) [START_REF] Winkler | Cancer profile of migrants from the Former Soviet Union in Germany: incidence and mortality[END_REF]. The cancer mortality among Polish immigrants in France was studied by Tyczynski et al. [START_REF] Tyczynski | Cancer mortality among Polish migrants to France[END_REF]; no significant trends were observed in men, while lower overall cancer mortality was shown in Polish immigrant women (RR 0.95, p<0.05).

In France, in contrast to other western countries such as the United States of America, the United Kingdom or Sweden, the burden of TRCs in migrants has been little studied. These studies, mainly conducted in the 1990s, found lower cancer mortality in immigrants in

France [START_REF] Bouchardy | Cancer mortality among north African migrants in France[END_REF], Bouchardy et al., 1995[START_REF] Bouchardy | Cancer in Italian migrant populations[END_REF], despite a higher prevalence of smoking in immigrants than in French nationals (Wanner et al., 1995b). The 1 st study on migrant mortality in France showed that the mortality of migrants was unexpectedly lower than in the natives, but also lower than in the corresponding occupational categories in France [START_REF] Darmon | An overview of the health status of migrants in France, in relation to their dietary practices[END_REF]. In a later study the authors observed also a lower morbidity in North African immigrants, although the prevalence of smoking in men was similar to that in the natives [START_REF] Khlat | La morbidité dans les ménages originaires du Maghreb, sur la base de l'enquête Santé de l'Insee, 1991-1992[END_REF].

In et al., 2014). However, another study showed a higher incidence of lung cancer in immigrants or descendant men from either a western or a non-western country and in immigrant and descendant women from a western country; in immigrant women from non-western country, the trend was not significant [START_REF] Dalton | Social inequality and incidence of and survival from lung cancer in a populationbased study in Denmark, 1994-2003[END_REF]). An earlier study, in Denmark, comparing cancer incidence between migrants and natives showed differences by type of cancer and country of birth of the migrants. Migrants from East Europe had similar overall cancer incidence than the native Danes, while Middle East and North African migrants had lower incidence. Further, the natives of Denmark had a higher incidence of breast and colorectal cancer compared to immigrants overall, whereas East European immigrant men had a higher incidence of lung cancer [START_REF] Norredam | Cancer incidence among 1st generation migrants compared to native Danes--a retrospective cohort study[END_REF].

This literature review on cancer in immigrants in Europe indicated that the majority of the studies observed lower overall cancer and all TRCs incidence and mortality rates in immigrant populations compared to the natives in European countries. However, the incidence and mortality rates of TRCs in immigrants did differ by specific TRC site, country of origin, sex, and, to a lesser extent, by host-country. Turkish immigrants had a lower incidence of cancer overall and TRCs, but the lung cancer burden was higher in Turkish men than in the natives of the respective host countries. Similarly, the cancer incidence and mortality was lower in African immigrants than in the natives, but increased rates of liver, bladder or oesophagus cancers were observed in several studies. In Asian immigrants, lower overall cancer mortality and incidence rates were observed consistently. Nonetheless, there was still evidence of elevated liver, bladder, stomach and oral cavity cancer rates compared to the European natives. For immigrants from other European countries and the Former Soviet Union, the patterns for cancer and TRCs were less clear with no significant trends observed.

RATIONALE

International migration

International migration is increasing globally with 232 million persons estimated to be living outside their country of birth in 2013 (United Nations, 2013). Figure 1.3 shows the heterogeneous distribution of international migrants worldwide. These international migrants represented around 3% of the global population. Fifty years ago, migrants were In 2012, the incidence and mortality of the main eight TRCs associated with smoking, including laryngeal, lung, lower urinary tract (pelvis, ureter, and bladder), oropharynx, oesophagus, oral cavity, liver and stomach cancers, was shown to vary greatly by countries or regions [START_REF] Ferlay | GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase[END_REF]. Globally, the eight main TRCs represented about half of the total number of cancers (47.9%) and 58.9% of the cancer deaths. However, it should be noted that these cancer sites have competing risks which would affect the total number of cases or deaths. Further, mortality can be influenced significantly by treatment and access to treatment after cancer diagnosis which can vary greatly by country. Therefore, the number of TRC cases or deaths caused by tobacco would be lower. This pattern differs between more developed regions (all regions of Europe plus Northern America, Australia/New Zealand and Japan) and less developed regions. On one hand, in more developed regions, the incidence of the eight main TRCs was 36.8%, and their corresponding mortality was 49.4%. While in less developed regions, the burden of the main TRCs was significantly higher in incidence and mortality, at 56.2% and 66.3% respectively. This difference in cancer burden between countries is showed in the Figures 1.9 and 1.10 (Ferlay et al., 2013), with the example of the lung cancer incidence in men and in women. These figures also illustrate the gender gap that existed in the lung cancer incidence by country in 2012. For most of the countries, the estimated lung cancer incidence was higher in men than in women. In the EU-28, the incidence and mortality of the main 8 TRCs in 2012 accounted for 34.9% and 47% of the total burden of cancer respectively [START_REF] Ferlay | GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase[END_REF]. The French estimates were similar to those of EU-28, with the 8 TRCs representing 31.9% and 46.9% of the total incident cases and deaths. The Danish TRC burden was below the European average, with 29.1% and 42.5% of the total cancer incidence and mortality.

Tobacco-related cancers

HYPOTHESES AND OBJECTIVES OF THE THESIS

Evidence has shown that the norms and traditions of the countries of origin have a continuing influence on the behaviour of migrants after settling in their host countries.

Therefore we hypothesize that the tobacco use differs in immigrants compared to the natives. Furthermore, we expect that the tobacco use prevalence -including cigarettes, cigars and shisha smoking, as well as use of snuff and chewing tobacco -among migrants shows a pattern similar to the prevalence in the countries of origin. More specifically, migrants from a country with particularly low tobacco use prevalence are expected to use tobacco less than migrant groups coming from countries where tobacco is commonly used or than natives of the host-country with high tobacco use prevalence.

We also expect acculturation to modify home country behaviours imprinted by their original cultures and norms. Among the broad group of migrants, it is often seen that second generation migrants or those who migrated at a young age or resided for a long period in the host-country are more successful in terms of educational and economic development. We hypothesize that migrants who migrated at a younger age or resided longer in the hostcountry and second generation migrants will be more similar to the host population in their tobacco use prevalence than those who migrated later in life or resided a shorter period in the host-country in Europe where smoking tends to be high or historically has been high. This is of particular importance in view of the large disparity in the gap in smoking prevalence between men and women which is still very large in developing countries, while in developed countries it has decreased to a large extent. Other research showed that more assimilated men smoke less, while more assimilated women smoke more, thereby decreasing the gender gap (Reiss et al., 2014b). We therefore expect that the 'gender gap' in smoking prevalence will be smaller among migrants than in their countries of origin, but still larger than among the European-born. The discussion (Chapter IV) summarises the results of this thesis with its strengths and limitations. The results from these two studies provided insight into the burden of tobacco in migrants compared to the natives in Europe, and to identify gaps in knowledge to be investigated in further studies. In this concluding chapter, a critical reflection and perspectives of future research -including methodological remedies -are presented.

CHAPTER II: TOBAMIG A FEASIBILITY STUDY 1 OBJECTIVE

To address the lack of data on tobacco use and determinants of use in immigrants in

France, the TOBAMIG pilot study aimed to develop a protocol and test the feasibility of collecting information on tobacco use in a sample of this population minority group. The pilot study was conceived as a preliminary step to evaluate the feasibility of undertaking a full-scale study of tobacco use in immigrants in the country.

To achieve its main objective, TOBAMIG aimed:

1) to develop an approach to identify a representative sample of the immigrant population in Lyon Metropole;

2) to ascertain the feasibility of conducting private interviews of the target population in public places;

3) to assess the potential study participation; preceded by a short background to the study that includes details on the immigrant populations and their health, as well as tobacco use behaviours in France. Additional information on the study methodology and the results are also presented. Some minor repetitions of the information found in the article are included in this chapter to help the reader understand the additional material in this section. The conclusions of the study can be found in the manuscript.

BACKGROUND

The French immigrant populations

In 2014, France had the 3 rd largest share (7.6

Tobacco use behaviour in France

For more than [START_REF] Bodenmann | Perception of the damaging effects of smoking, and brief cessation counselling by doctors[END_REF]

METHODS OF THE PILOT STUDY

Population groups

In France, the High Council for Integration (HCI) recommended the use of a specific definition for an immigrant: a person born abroad of foreign nationality at birth, excluding a foreign-born person born abroad of a French nationality. In terms of studying acculturation and health behaviours, the definition of the HCI is relevant as a French person born abroad is not expected to differ from the French natives as much as a foreigner born abroad.

Consequently, the descendants of immigrants, also called 2 nd generation immigrants, are the persons born in France from one or two 1 st generation immigrant parents.

Furthermore, in our study we focused on adult immigrants, aged 18 years and over, as tobacco use in adolescents may be different from that in adults. Additionally, it would have required ethical approval by the CNIL and signed consent from their parents or responsible adult to include minors in the pilot survey.

The targeted population was limited to immigrants of non-European origins because the use of tobacco in other European countries is generally more similar to that in the French general population and better described in the literature than tobacco use in other principal countries of origin of immigrants in France.

Sampling approach

To increase the probability of reaching the population of interest in the metropolitan region of Lyon, the 5 municipalities with the largest proportion of African or Asian immigrants were chosen to conduct the survey, as well as a district of Lyon. To obtain a representative sample of the immigrant population residing in the selected municipalities in terms of sex, age, education and country of origin, a combination of different types of location was chosen to reach the target population. The different types of venues were:

1) street markets 2) public and private primary schools (to recruit parents) 3) bars and restaurants 4) Universities and colleges 5) shop fronts with international phone facilities ("phone parlors") 6) residences specifically accommodating disadvantaged families or single immigrant workers known as Adoma residences, and 7) community arts centres and youth clubs "MJC". Large shopping centers were added later. For each type of location we randomly selected 2 venues for the trained interviewers to contact potential responders. We aimed to conduct 100 interviews in total, with the number of administered questionnaires equally distributed across the 16 different venues. Four interviewers were trained to recruit and administer the questionnaire to eligible responders.

Sampling approach

The sampling method used in this pilot study falls under the definition of a "convenience sampling". A convenience sample is a sample that uses individuals or sample units that are readily available rather than those that are selected to be representative or selected via a probabilistic mechanism [START_REF] Li | Convenience Sample[END_REF]. Although convenience sampling is, like the name suggests -convenient -it runs a risk that the sample will not be representative of the population. Nevertheless, a convenience sample is sometimes the only way to efficiently recruit participants. Convenience sampling is a type of non-probability sampling -i.e.

where participants are randomly selected, and each has an equal chance of being chosen. With non-probability techniques, the randomness element is absent. However, convenience sampling does have its uses, especially when it is needed to conduct a study quickly or on a tight budget, and also when representativeness is not necessarily needed.

It is also one of the only methods one can use when a list of all the population is not available. In its basic form, convenience sampling method can be applied by stopping random people on the street and asking questionnaire questions. Although the use of this sampling technique is discouraged in epidemiological research due to inability to generalise research findings -because the sample does not truly represent the larger target population -this sampling technique may prove to be effective during exploration stage of the research area, and when conducting pilot data collection in order to identify and address shortcomings associated with questionnaire or sampling design.

Furthermore, validity of convenience samples can be increased by approximating random selection as much as possible, and preventing the introduction of potential bias into the sample selection.

In this regard, the TOBAMIG methodology was designed to interview a large set of respondents' profiles depending on the recruitment type of locations: younger/older, more/less educated, men/women; hence, recruitment of a mixed sample was considered more important than having all groups represented in the sample according to their proportion in the underlying immigrant population (i.e. in a stratified sample).

Additionally, exhaustive lists of each type of locations (i.e. street markets, primary schools, bars and restaurants, Universities and colleges, phone parlors, social residences, community arts centres and youth clubs "MJC", and large shopping centers) were built for the target sampling area, in which 2 locations were randomly selected for each type.

In the absence of a population register that would allow identification and recruitment of immigrants, the TOBAMIG methodology introduced randomness in the sampling as well as a wide range of type of places to minimize the effects of the convenience sample, and allow making valid inferences about the larger group from which they are drawn.

As Prior to the implementation of the pilot study, the questionnaire was tested on a convenient sample (n=10) of both target and non-target population that included different tobacco user profiles. This testing allowed for adjustment and corrections of the skip pattern as well as corroboration of the clarity of the questions being asked and estimation of the questionnaire's administration time.

Evaluation

Attention was paid to different aspects of the completed pilot study. The sex, age, generation and country of origin distributions of responders in the pilot was compared to the distribution of these attributes in the population of immigrants in the selected municipalities of the Lyon Metropolitan area from which the sample was drawn. The

OVERALL AND ADDITIONAL RESULTS

In addition to the results presented in the article, we also found that our pilot study represented an innovative method to investigate tobacco use and related determinants in 1 st and 2 nd generation immigrants in selected municipalities of Lyon Metropole. Our sample was similar in most of its demographic characteristics to that of the immigrant population in the sampling area. The main country of origin of both generations' immigrants in our sample was Algeria (29%). We observed a proportion of current tobacco smokers (45%) above that of the general population of France (34.1%). A large gender gap was also observed: more men were smokers than women, respectively 35.6% and 27.9% in the general population, and 51% and 38% in our sample. In our sample, the proportion of shisha users was twice higher than in the general population: 15% versus 7%.

Table 2.2: Characteristics of interviews by type of venue for the 2 main interviewers

Out of four interviewers two administered the majority of the questionnaires (77%).

CHAPTER III: TOBACCO-RELATED CANCERS IN AN IMMIGRATION PERSPECTIVE 1 OBJECTIVE

In this chapter, the aim was to compare the incidence of TRC in men living in Denmark, depending on their migration status (natives and immigrants). A secondary objective was to investigate whether the TRC patterns observed in 1 st and 2 nd generation immigrants corresponded to the patterns of tobacco use in the respective countries of birth.

The related scientific manuscript (published online in Acta Oncologica on 27 th March 2015) is included below. Prior to the manuscript, an overall presentation is given, including complementary information about the background, method and results of this study.

Limited repetitions of information that can be found in the article are presented for the understanding of the additional details in this section. The conclusions of the study are given in the manuscript.

BACKGROUND

In Denmark, 53% of all 1 st and 2 nd generation immigrants originated from a European country in 2014 (Statistics Denmark, 2015). Previously, foreign-born people who migrated to Denmark originated mainly from neighbouring Nordic countries or other European countries, and to a lesser degree from Turkey and the former Yugoslavia.

During the 1980s and 1990s, an increasing number of immigrants came from Asia and the Middle East (e.g. Iraq, Iran, Afghanistan and Pakistan) or Africa (e.g. Somalia and Ethiopia). As shown in Figure 3.1, the main country of origin in 2015 was Turkey; 9.4% of all immigrants and their descendants, or a total of 61,634 persons. Poland and Germany are the 2 nd and 3 rd most common countries origins for immigrants and descendants, with respectively 6.0% and 4.9%.

Tobacco use in Denmark

In Denmark, the smoking prevalence in men has decreased from more than 70% in the1950s and 1960s to less than 30% in 2010 [START_REF] Clemmensen | Nationwide tobacco surveys and sales data in Denmark from 1920 to 2010[END_REF]. In women, the prevalence of tobacco smoking peaked in the 1970s around 45%, and decreased to about 24% in 2010. In 2014, 21% of Danes were current smokers. The proportion of those who smoke daily was constant at 17%, and there was no difference in the proportion of daily smokers between men and women (Danish Health and Medicines Authority, 2014).

One in three (34%) Danish people had tried waterpipe smoking at least once or twice in 2014; amongst which 8% were current regular (1%) or occasional (7%) waterpipe smokers (European Commission, 2015a).

The prevalence of smokeless tobacco use in Denmark was 2% in 2010; 3% in men and 1% in women (Danish Health and Medicines Authority, 2010).

This study is a register-based cohort study, using data from the Danish Civil Registration System and from the Danish Cancer Registry, collected initially for a testicular cancer cohort study [START_REF] Schmiedel | Testicular germ cell cancer incidence in an immigration perspective, Denmark, 1978 to 2003[END_REF]. For all men living in Denmark between 1978 and 2010, information on date and place of birth, migration and death, were retrieved from the Danish Civil Registration System. With the help of a unique personal identification number (CPR), this information were linked to the cancer data, including cancer code following the International Classification of Diseases, version 10 (ICD-10).

Population groups

In Denmark, '1 st generation immigrant' commonly refers to a person born outside of Denmark. Persons born in Denmark can either be 'natives' if both of their parents were also born in Denmark or '2 nd generation immigrant' if one or both of the parents were born abroad.

For 15% of the 1 st generation immigrants, the date of immigration was missing and therefore 49,895 1 st generation immigrants were excluded from the main analysis. We provide here additional details on this group of 1 st generation immigrants.

Cancer codes

All primary cancers -excluding non-melanoma skin cancers -were retrieved from the national cancer registry. We selected 9 major TRC types according to their smoking

Statistical methods

In order to compare TRC incidence among 1 st and 2 nd generation immigrants to that in the native Danes, we calculated Standardized Incidence Ratios (SIR) and 95% confidence intervals (CI), using five-year age group and one-year time intervals. For each migration status, the SIRs were stratified by region or country of birth and by TRC.

Incidence rates of the nine selected TRC combined and of lung separately were standardised according to the World Standard Population (R et al., 1966). The rates were smoothened by three-year intervals to mitigate the fluctuations due to small number of cases in 1 st generation immigrants. The numbers were too small in 2 nd generation immigrants, and therefore not reported. Lung cancers age-standardised rates were compared graphically between 1 st generation immigrants and natives, over the cohort time period (from 1978 to 2010). The overall TRC age-standardised rates in the same 2 groups were compared by age-group.

OVERALL AND ADDITIONAL RESULTS

In our cohort study, during up to 32 years of follow-up, we identified 131,317 TRCs among 3,508,204 men, including 280,526 1 st generation and 129,056 2 nd generation immigrants. Overall, immigrants of both generations experienced an approximately 15% lower incidence of TRC than natives, although there were large variations by type of TRC and country of birth.

Compared to natives, 1 st and 2 nd generation immigrants had 10% and 27% lower incidence, respectively, of lung cancer, with Asian males experiencing the lowest incidence. First generation immigrants had an about 50% lower incidence of lower urinary tract cancer than natives. Only liver and stomach cancer were observed in excess among immigrants. Incidence of lung cancer along the study period increased in 1 st generation immigrants reaching the level of that of native Danes in the mid-2000s.

Subgroup of 1 st generation immigrants without immigration date

In the main analysis used for our manuscript below, 1 st generation immigrants without immigration date were excluded (n=49 891). Given the large size of this group, we investigated how the results would change if they were included in the analyses. Table 3.1 shows the distribution of this subgroup of 1 st generation immigrants by country or region of birth. In this subgroup, 2 323 cases of the nine selected TRC were diagnosed, as shown in Table 3.2. As the mean year of birth in this subgroup was substantially earlier than in the rest of the 1 st generation immigrants (1943 vs. 1967), we included this subsample in the cohort with imputation of their date of entry as 1 st January 1978, or their date of birth if occurred after. They were followed up, similarly to the rest of the cohort, until 31 December 2010, date of diagnosis of a selected TRC or date of death, whichever came first. Table 3.3

presents SIRs by region of birth for the nine TRC overall and for lung cancer, for the whole cohort, including the subgroup of 1 st generation immigrants with missing immigration date.

The addition of the 1 st generation immigrants with no immigration date to the analysis does not induce major changes in the results, compared to the rest of the 1 st generation (as presented in the article below). However, there are exceptions, for instance the statistically significant excess of lung cancer incidence in European immigrants that disappears (SIR=1.11 to SIR=0.98). Overall, the incidence of all selected TRC combined is approximately 10% lower in 1 st generation immigrants than in the natives (SIR=0.89, p<0.05) (cf. Table 3.3). Noticeably, immigrants born in Turkey have a similar incidence of lung cancer compared to the natives (SIR=1.07 vs. SIR=1.5 without the 1 st generation immigrant with no immigration date).

Table 3.4 shows that the incidence of all other TRC, but pancreas cancer, in all immigrants (with or without immigration date) is significantly different: lower in the 1 st generation immigrants than in the natives for larynx, bladder, oropharynx, esophagus and oral cavity cancers; higher for liver and stomach cancers. These figures differ from that of the article's analysis in larynx cancer incidence being significantly lower (SIR=0.84, p<0.05). Furthermore, the addition of the subgroup of immigrants reduced the SIRs' values: the incidence of the 1 st generation immigrants' TRCs is actually closer to that of the natives when including the group of 1 st generation immigrants with no immigration date. Similarly, the inclusion of the 1 st generation immigrants with no immigration date in the cohort has not changed the direction of the results, but the magnitude of the differences with the natives is affected. For instance, the high incidence of laryngeal cancer observed in immigrants born in the Former Yugoslavian countries is less high than in the main analysis (SIR=1.8 vs. SIR=2.6).

RECALL OF THESIS OBJECTIVES

The aim of this thesis was to provide insight into the tobacco use and related cancer burden in immigrants compared to the natives in the European host-countries. This objective was addressed with two literature reviews and two distinct studies, in order:

 to explore tobacco use and determinants of use in immigrants in France by testing a study protocol and data-collection instrument (TOBAMIG feasibility study, Chapter II).

 to compare the burden of tobacco-related cancers between immigrants and natives in Denmark (Danish nationwide cohort study, Chapter III).

 to put these results into context with current knowledge on tobacco use and tobacco-related cancer occurrence and mortality in immigrant populations in Europe (Chapter IV).

 to describe limitations of the studies and give guidance of how to set up a study on tobacco use and cancer risk in immigrants in France (Chapter IV).

The TOBAMIG pilot study aimed specifically 1.1) to ascertain the feasibility of conducting private interviews of the target population recruited in public places, 1.2) to evaluate an approach to identify the immigrant population in Lyon Metropole, 1.3) to assess the participation to the study and 1.4) to pilot a questionnaire on tobacco use developed for the study.

The specific objective relating to the Danish cohort study was to compare the incidence of TRCs among male immigrants of first and second generation in Denmark with incidence among males in the native Danish population.

RESULTS

Several conclusions may be drawn from the results of each individual element of this thesis, as well as the work in its entirety. These learnings are presented below.

Literature review on tobacco use in immigrants in Europe

The first learning garnered from both literature reviews on tobacco use and on tobaccorelated-cancer burden in immigrants in Europe is that despite increasing immigrant populations, little is known about immigrants' health and lifestyle trends as they relate to cancer risk in European countries. Furthermore, studying a demographic sub-group, which comprises a small proportion of a nation's population, comes with challenges that have been approached differently, depending to a large extent on the population-based resources available in the country of interest. From the 1 st literature review we identified various sampling methodologies used to identify and recruit immigrants in epidemiologic studies investigating tobacco use. Registry-based study protocols [START_REF] Pudaric | Major risk factors for cardiovascular disease in elderly migrants in Sweden[END_REF][START_REF] Van Oort | Determinants of daily smoking in Turkish young adults in the Netherlands[END_REF] where immigrants and natives could be singled out, offered a straight forward approach to reach the target population and ensure representativeness, as data are routinely collected and the sample size is generally large, if not nationwide.

The representativeness of such studies is a clear asset. Due to the lack of such registries in the countries where studies on immigrants have been conducted, identification through household or public places surveys was a commonly used sampling method [START_REF] Aspinall | Smoking prevalence and the changing risk profiles in the UK ethnic and migrant minority populations: implications for stop smoking services[END_REF][START_REF] Hosper | Behavioural risk factors in two generations of non-Western migrants: do trends converge towards the host population?[END_REF][START_REF] Ezika | An exploration of smoking behavior of african male immigrants living in glasgow[END_REF][START_REF] Kabir | Smoking characteristics of Polish immigrants in Dublin[END_REF]. This approach, however, requires building study specific sampling frames and sampling strategies, as well as adapted instruments to collect the tobacco use information. In the latter approach to immigrant studies, the representativeness of the sample was not always reported. This gap in reported information limits the generalizability of stated findings.

No studies were identified with a sampling approach similar to that employed as part of the TOBAMIG pilot study. Our methodology required the construction of a sampling frame and setting priority rules for sampling municipalities where non-European immigrants resided. Indeed, our sample was representative in terms of sex, country of birth and distribution by migration generation of the total population of immigrants living in the sampled municipalities. In the future, this method could be adjusted to sample immigrants in different parts of France. This would enable the construction of a sampling frame which would be representative of the broader immigrant population of France, especially useful where no access to census information is available. On the other hand, our approach identified large and frequently transited public venues as the most efficient locations for identifying and enrolling responders. Nevertheless, with greater

Literature review on cancer and TRC in immigrants in Europe

Although many studies on TRCs in immigrants were identified as part of the 2 nd literature review, it was clear that there is still much to be explored. Again the sample sizes -from few hundreds (Mousavi et al., 2012b) to approximately 1.8 million immigrants (Hemminki et al., 2010a) -and varying definitions limit our understanding of the variations in TRC burden in immigrants. The majority of the studies observed a lower incidence and mortality of overall cancer rates and of TRCs overall in immigrant populations compared to the natives in the European countries. As for the smoking prevalence, the burden of TRC in immigrants depended on the country of origin, sex, and to a lesser extent on the host-country. Differences were also seen according to cancer site. For instance, Turkish immigrants had a lower incidence of cancer overall and TRC, but the lung cancer burden was higher in Turkish men than in the natives of the respective host countries. Similarly, the cancer incidence and mortality in general and TRC, in particular, was lower in African immigrants than in the natives, but increased rates of liver, bladder or oesophagus cancers were observed in several studies. In Asian immigrants, lower mortality and incidence of all-site cancer was observed consistently across all studies, however, elevated rates of liver, bladder, stomach and oral cavity cancers were shown compared to the European natives. Patterns of cancer and TRC were less clear and no significant trend was observed in western immigrants, mostly from other European countries and the Former Soviet Union.

TOBAMIG feasibility study

Ideally, exploring tobacco use in immigrants requires a study using a validated protocol.

The TOBAMIG pilot study tested the feasibility of investigating tobacco use and its determinants in 1 st and 2 nd generation immigrants in the French metropolitan area around Lyon. In the sampling area, the study sample was shown to be similar to that of the immigrant population in terms of demographic characteristics. Nevertheless, some minor differences were observed in the distribution by generation or by country of origin. Our pilot sample included a higher number of immigrants of other African origin than the population in France. Based on 75 subjects, the questionnaire data revealed a smoking prevalence above that of the general population in France -45% and 34%

respectively -with a gender gap: more men were smoking than women, 36% and 28% in the general population respectively, and 51% and 38% in our sample. Additionally, the prevalence of current shisha users was twice as high as in our sample compared to the general population, respectively 15% and 7%.

The length of administration of the interviews revealed to be inadequate as not all sections of the questionnaire were fully completed, due to the settings of anonymous interviews conducted at fortuitous visits in public places. In particular, the anonymity of the questionnaire did not allow for follow up of missing responses. This indicated that the questionnaire should be shorter to improve response to a study using a recruitment strategy of intercepting people in public places. Additionally, high-frequentation venues provided the required anonymity to administer the questionnaire. With modifications, this pilot study protocol can be used to recruit a sample of immigrants which can be representative of the population in France. Finally, in this limited sample, the preliminary findings on tobacco use suggested disparities, that are generally higher rates, in tobacco use between our sample and the French general population.

Danish cohort study on TRC in immigrants

The Danish cohort study showed an overall 15% decreased incidence of the nine selected major TRC in male immigrants compared to Danish male natives. Generally, the SIR for each selected TRC varied according to the prevalence of smoking and smokeless tobacco use in regions and countries of origin, suggesting that the smoking patterns from an immigrant's country of origin may have a primary role in the burden of TRC in Denmark.

Nevertheless, our analysis did not have access to data on tobacco use at the individual level and thus we can only suggest, at best, possible explanations for the observed trends. A high incidence was observed among non-European immigrants for liver and stomach cancers in line with several previous studies. Unexpectedly, a lower incidence of TRC was seen in some immigrant groups compared to the native Danes, notably for lower urinary tract cancer. The increase in bladder cancer in native Danes could be due to differences in the occupational exposures. Workers with aromatic amine exposure have been shown to have the highest incidence of bladder cancer, while those exposed to polycyclic aromatic hydrocarbons and heavy metals had the greatest mortality [START_REF] Cumberbatch | Contemporary Occupational Carcinogen Exposure and Bladder Cancer: A Systematic Review and Meta-analysis[END_REF].

Overall results

This thesis contributes new knowledge on immigrant health in one European country, Denmark, specifically on cancers associated with tobacco use and on a potential sampling approach to identify and interview immigrants to document tobacco use, particularly in Lyon, to inform the design of a study to investigate this knowledge gap in France. We have shown in Denmark that immigrants overall had a lower incidence of the main TRC compared to the natives. This finding is in line with the literature in other European countries. But we also showed that this lower rate of TRC overall implies diverging cancer incidence trends in relation to immigrant sub-groups according to the country of origin and the cancer site. Consistently with the literature that is summarized in the 2 nd review on cancer in immigrants, we observed that non-western immigrants had higher incidence of liver and stomach cancer which are also caused by infections (International Agency for Research on Cancer, 2012a). The prevalence of diseases caused by infections is especially high in low and middle income countries and immigrants from these countries. Another important finding in our study is the decreasing difference in incidence of lung cancer over time between immigrants and natives in Denmark. The size of the Danish cohort (n=3,508,204) was a unique asset to show the trends in cancer incidence in the different immigrant sub-groups including country of origin, generation and histologic sub-types.

Further, this study highlighted the probable role that tobacco exposure plays in the morbidity of the immigrant populations in the host-country. To our knowledge, no previous studies have focused on investigating the link between the tobacco use and TRC burden in immigrants in Europe, in spite of the increasing proportion of immigrants and the potential of tobacco control to reduce the cancer burden worldwide and in Europe.

We have proposed that TRC incidence in Danish immigrants corresponds to the level of the smoking and smokeless tobacco use in their countries of origin. Although it was not the objective of our study to assess this association, this finding deserves further investigation. Additionally, cancer development is a complex and long process and former prevalence of smoking or smokeless tobacco use is an indicator of the current risk of TRC, whereas current prevalence predicts the future burden. TRC cancer risk is also dependent on other factors, including the age of starting smoking, the duration of tobacco use, the intensity of its use, as well as other etiologic agents contributing to development of TRCs, e.g. infectious diseases or genetic factors. Therefore, the trends in TRC incidence that we observed in the Danish immigrants in relation to the level of the current tobacco use prevalence in the countries of origin should be interpreted with caution. This study also underlines the unique possibilities for research in immigrants' health presented through the use of population registry-based data [START_REF] Norredam | Register-based studies on migration, ethnicity, and health[END_REF], even without information on individual tobacco use.

To address the lack of information on tobacco use in immigrants in the European countries, researchers have been challenged to design epidemiologic studies inclusive of these minority groups. Developing and assessing a protocol to investigate a behaviour which impacts health -tobacco use in our case -in a minority group presents several challenges. Firstly, the identification and effective recruitment of immigrants give rise to consideration of the representativeness of the sample; further, it may also imply certain ethical or legal considerations to avoid stigmatizing a population's lifestyle. Our review showed that the literature on the tobacco use in immigrants in Europe was scarce (n=33 original studies). Approximately half of these few studies used established population registers, such a municipality register entailing immigration status and/or country of birth recording, to identify immigrants. Identification through household or public places surveys is difficult, consequently, the number of studies is limited.

In the French context, where registries including information on country of birth are not available, we opted to develop an innovative research protocol. Our method incorporated some elements of existing studies, e.g. use of trained interviewers from the target immigrant group to be sampled posted at public places known to be frequented by the immigrant population [START_REF] Kabir | Smoking characteristics of Polish immigrants in Dublin[END_REF]. However, our sampling approach is unique in using a variety of locations known to be attended by immigrants, located in municipalities with high proportion of immigrants, and selected in order to capture different demographic profiles to ensure an overall sample representative of the immigrant population from such municipalities. Unfortunately, the use of incentives for re-contact with participants of the first round of interviews was unsuccessful in our study, while it showed to be effective in Germany in a community-based sampling strategy (Reiss et al., 2014a).

Although the TOBAMIG feasibility study had a limited sample size, our preliminary estimates of tobacco use were in line with the literature from the 1 st review. Indeed, a higher prevalence of smoking was observed in our sample, constituted mainly of North African and Turkish immigrants, than national values for the French population reported in recent surveys [START_REF] Guignard | La consommation de tabac en France en 2014: caractéristiques et évolutions récentes[END_REF]. Further, the smoking prevalence was higher in men than in women as observed in other studies [START_REF] Reiss | Imported risk' or 'health transition'? Smoking prevalence among ethnic German immigrants from the Former Soviet Union by duration of stay in Germany -analysis of microcensus data[END_REF][START_REF] Jorgensen | Migration and smoking: an epidemiological study of Finnish twins in Sweden[END_REF]. Our data on tobacco use in the 1 st generation immigrants therefore confirm results from older studies using different sampling methodologies (Wanner et al., 1995b, Berchet and[START_REF] Berchet | Health status of first-and second-generation migrants in France[END_REF]. Although our feasibility study contributed new knowledge on tobacco use in showing a higher smoking prevalence in the 2 nd generation immigrants, and a high prevalence of shisha users in this 2 nd generation, these estimates are derived from a limited number of subjects and thus these last findings require confirmation in studies with larger sample sizes.

Finally, both existing studies identified in the literature and our results showed that inequalities in health related to tobacco exposure are pronounced between the immigrant group and the natives of the host-countries, that is, with higher incidence in natives, overall. Further, these inequalities exist within the immigrant group, depending on country of origin, sex, site-specific, between the 1 st and the 2 nd generation immigrants, and to a lesser extent on the host-country.

STRENGTHS AND LIMITATIONS

This thesis addresses the lack of knowledge of immigrants' use of tobacco, a major determinant of health, and on the burden of tobacco use as illustrated by overall cancer incidence and tobacco-related cancer when compared to natives in the host country.

Chapter I confirmed the scarcity of current literature on tobacco use in immigrants in Europe, which is concerning considering the increasing phenomenon of international migration. In Europe, few countries, such as Denmark, Germany, the Netherlands, Sweden and the United Kingdom, have studied this issue. However in other countries, including France, very little is known, although the 1 st and 2 nd generation immigrants can represent nowadays one person in five in the whole population. This is surprising considering that France is the European country with the largest proportion of 1 st and 2 nd generation immigrants overall (INSEE, 2012b, European Commission, 2008).

The TOBAMIG pilot study -described in Chapter II -is one of the rare studies in France that has attempted to address tobacco use in the immigrant population. Our study developed a methodology to explore the tobacco use in both generations of immigrants, including all forms of tobacco use, determinants of use as well as other related domains.

Further, it is also the only study on tobacco use in immigrants in France conducted with face-to-face interviews in public places; previous French studies were household national surveys (Wanner et al., 1995b, Berchet and[START_REF] Berchet | Health status of first-and second-generation migrants in France[END_REF]. One of TOBAMIG's major strengths was to develop an extensive sampling methodology along with a comprehensive questionnaire. It has shown that, with certain modifications, this protocol has the potential to be implemented in a large-size study on a nationwide scale with high prospects of obtaining a representative sample of immigrants in France.

The length of administration of the questionnaire is considered a reason of a low participation as the approximate time of compilation was announced by interviewers to prospective responders when inviting to participate. Also, reduced completeness of the questionnaire was seen when responders, in several occasions, left questions unanswered towards the end of the questionnaire.

Not including French natives in the sample precluded a direct comparison of their patterns of tobacco use with that of immigrants. Including natives would also have mitigated any possible potential stigmatisation when interviewing participants in lowfrequentation venues, as interviewing non-European immigrants on their tobacco behaviours in a public places could be perceived as discriminating. Another limitation of this pilot study is the lack of participation data, overall and by type of venues, i.e. the number of persons willing to respond the questionnaire among all those who were approached was not recorded by the interviewers. This information would be important to assess the effectiveness of identifying and recruiting the target population at specific types of venues, as well as the rate and type of refusals which could hypothetically be a function of smoking prevalence of potential respondents in a given area. Nevertheless, the sampling at different types of venues indicated, based on the recruitment time, and other feedback provided by the interviewers, which venues were not ideal and which ones were better, such as markets, universities and large shopping centers.

In Chapter III, the study on comparing TRC incidence between natives and immigrants in Denmark showed the potential of high-quality register-based cohort studies. Large registry-based cohorts have sufficient sample size to show differences of TRC incidence by country of origin. Even if an overall lower incidence of the selected TRCs was observed in immigrants in Denmark, I demonstrated that immigrants are not an homogeneous population and that differences in TRC incidence existed by country of origin. Again exploring these differences was only made possible by the large data set of a national cohort for a 30 years-period. However, national registers are not without their limitations. The estimated SIR on a period of more than 30 years may mask possible yearly fluctuations. Further, the exclusion of 15% of the sample for which the date of immigration was unknown might have introduced bias. However, the exploration of TRC incidence in this subgroup did not reveal major differences with the rest of the 1 st generation immigrants that was included in the main analysis. The added value for research using register data does not need to be confirmed further but the missing date for 15% of our large sample highlights the need of quality assurance in such databases.

Immigrants' health inequalities are in part attributable to socioeconomic circumstances, making the two concepts closely interrelated but still distinct [START_REF] Stronks | The complex interrelationship between ethnic and socio-economic inequalities in health[END_REF].

As presented earlier, conflating migration status and social class, fails to fully unravel the relationship between differences by country of birth, socio-economic and health inequalities [START_REF] Lorant | Ethnicity, socio-economic status and health research: insights from and implications of Charles Tilly's theory of Durable Inequality[END_REF]. However, immigrants often share lower socioeconomic conditions in the host-country (INSEE, 2014, INSEE, 2012b). Therefore, it is important to include the socio-economic information in relevant studies to determine the specific impact of the immigration status on population health and to assess the health inequalities attributable to the migration process. In this regard, in the registrybased Danish cohort study information on the socioeconomic status was not available.

This information was also partially lacking in the TOBAMIG questionnaire, as only proxies of socioeconomic status, such as education level and employment status, were included.

Collecting the income level would contribute to describing socioeconomic status, but it was decided not to include it in the TOBAMIG questionnaire as it could be perceived as intrusive, in addition to the other topics covered in the questionnaire.

To address these limitations and take full advantage of these thesis strengths, the next section outlines suggested potential remedies to these limitations for a future larger scale study on tobacco use and determinants of use in immigrants in France.

RECOMMENDATIONS

Few studies in Europe have investigated the tobacco use in immigrants, while differences in the prevalence and intensity are known to be significant by country of origin compared to natives of a host-country (World Health Organisation, 2015). The first step is therefore to develop standardised methodology. The TOBAMIG study originally aimed to investigate tobacco use and the determinants of use in immigrants in France. To inform this aim, and following IEC recommendations, we developed a feasibility study protocol to identify and recruit a sample of the non-European immigrant population in selected municipalities of Lyon Metropole, and to conduct private interviews of the target population intercepted in public places.

The lessons learnt from our feasibility study have implications for a future study on many different aspects of the study, i.e. anonymity, ethics, type of venues, length of questionnaire, inclusion of immigrants from any country of origin, etc. Below I address each of these aspects separately and present then two alternative study designs for future studies, with adoption varying depending on the breadth and the depth of the information sought, to better understand tobacco use and related determinants of use in immigrants in France.

Anonymity, legal approval and implications

Conducting health research in immigrants is considered a "sensitive" topic by the French National Ethical and Legal Committee (CNIL) and therefore individuals' rights are protected by the law and any research protocol has to be submitted for their authorization. The health research authorization is a long process to which there is an alternative: if the whole protocol is "strictly" anonymous, then researchers do not require the special authorization. Strict anonymity means that the researchers should not record any information on the responders that would allow their identification, either directly (names, addresses, phone numbers) or indirectly, which means that crossing of variables cannot allow identification of the respondent. The last has implications especially on immigrants with the recording of date of arrival in France and country of birth of the responders and his parents which could indirectly lead to their identification, especially in the case of small municipality or immigrant from a rare country of birth.

Consequently, we chose an anonymous protocol to speed up the implementation of TOBAMIG feasibility study but this did not come without its limitations. Despite the use of incentives, the feasibility study did not succeed in completing a re-interviewing of a sub-sample of responders one month after the first interview. This full anonymity condition by the CNIL also implied not having the possibility to recontact the participant neither to check responses to the questionnaire (if missing or for quality control), nor to administer additional questions (e.g. on complementary topics).

For a large scale study, one could reconsider this choice of anonymity as our method can be seen as a way for rapidly and independently gathering information on tobacco useor other health behaviors -in immigrants. Despite its benefits, the most significant downside was our inability to recontact original responders. in another survey on complementing aspects (e.g. cessation, economics, perceptions, etc.) when tobacco exposure is better known. These complementary topics could be explored in especially designed subsamples of a same study through administration of extra modules covering these themes.

Alternatively, opting for a non-anonymous study would allow maintaining the questionnaire in its long form, as re-contacting the responder would be then possible or an appointment for an interview of adequate duration could be accorded.

Target population

It The inclusion of French natives would be another asset to a large scale study as it would enable comparison between natives and immigrant subgroups in their tobacco uses. But this has to be considered also in terms of additional costs to the study.

Selection of venues

The type of venues to implement the survey was found to be a crucial issue. Greater participation was observed at venues offering greater anonymity and required confidentiality, also minimizing potential stigmatisation. According to our results, the selection of the type of venues should focus on highly frequented places. TOBAMIG implementation does not allow us to disentangle the reasons behind limited participation in low-frequented venues. We cannot determine if participation in the study was proportionate to the number of people passing by the venue or if there was an interaction of this low frequentation with a perception of lower confidentiality. Indeed, potential participants may have hesitated responding in a public venue if they had the impression that due to the relative silence and visibility in a low-frequented venue, their interview would not meet satisfactory confidentiality requirements. Inversely, the noise and agitation of a crowd can be reassuring at the time of deciding to engage into a private interview. However, in the case of the Adoma residences, the setting offered more confidentiality, although it is a low-frequented venue, and yet not many interviews were completed at this type of venue for which a greater coordination could render in the future a better rate of enrolment.

As a result, when conducting a larger scale study in a similar anonymous setting, I recommend concentrating on high-frequentation type of venues, such as markets, universities, large shopping centers and potential other similar places.

Interviewers

The next main consideration for a future study is the need of extensive training of interviewers, including greater familiarity with the questionnaire, the rigor of collecting all data in the questionnaire as well as keeping track of all subjects contacted and concomitant refusal rate. Also important is the selection of interviewers with sufficient experience. Interviewers' views on immigration should also be investigated before the study to ensure that they will not interfere with the conduct of the survey, particularly

regarding their perception of a potential stigma while administering questionnaires in public areas.

Individual interviews and focus group

A qualitative study of both the target population and the interviewers could be developed to assess why immigrants may not answer certain parts of the questionnaire and on the investigation of tobacco use in this population group from both perspectives:

the interviewer and the respondent. The objectives of this qualitative investigation would be to document separately the respondents' and interviewers' experiences, knowledge and beliefs about investigating tobacco use in the immigrant populations.

Two complementary methods could be used: individual interviews and focus group. This crossed approach enables to collect information to enrich the data collected by the questionnaire, to aid in the interpretation or in the understanding of certain patterns or issues, and the sampling and interviewing protocol. Individual interviews would involve participants from each demographic group based on the immigration status, country of origin and the participant's age and sex. Focus groups would be done to confirm what have been found in the individual interview. The community centers and local associations in the neighbourhood of the sampling area could be solicited in order to obtain a diverse sample of respondents.

Interviews would be conducted in the tradition of the phenomenological interview [START_REF] Thompson | The Lived Meaning of Free Choice -an Existential-Phenomenological Description of Everyday Consumer Experiences of Contemporary Married-Women[END_REF]. The interviews would be semi-structured and entail two parts:

1) collect data on general knowledge and experience on tobacco use in immigrants; and

2) use photo-elicitation -which uses images as a basis for open-ended interviewing (Heisley and Levy, 1991) -to gather responses and gain insight into interviewers' and respondents' understanding of the tobacco and immigration imageries.

The focus groups allow discussion during which the participants justify their choices and attitudes and so allow them to specify their representations and beliefs. A semistructured interview could be used to facilitate an interview situation but the questions should not be restrictive and the anthropological interview aims to discover the individual's pathway, the representative associations [START_REF] Kitzinger | The Methodology of Focus Groups -the Importance of Interaction between Research Participants[END_REF]. The interview leader will facilitate this exploration with the group. These interviews would result in rich insights into interviewers' and respondents' beliefs and perceptions of the tobacco and the immigration phenomenon and can reveal the social and cultural dynamics that affect these perceptions.

The individual and group interviews would be recorded and transcribed for qualitative analysis. The outcomes of the analysis would be: 1) a series of items to serve in the development or adaptation of the questionnaire; and 2) the identification of elements to be covered by the training of the interviewers and potentially an adaptation of the sampling protocol.

Representativeness

This anonymous feasibility study protocol indicated the approach used was effective to investigate tobacco use in a mixed sample of immigrants that is representative of the municipalities where the study was conducted. However, both was the immigrant population in our sampling area not fully representative of the national immigrant population and with the choice of venues for most efficient recruitment it became a convenience sample of immigrants, still informative for the purpose of our study . In the absence of national register including the immigrant status, it would be critical to combine different areas in France to obtain a sample representative of all types immigrants in the national mainland. The most promising approach is to obtain a stratified sample so that all immigrant groups are well represented in numbers to accurately estimate their tobacco use patterns, but for different groups different recruitment methodology could be used as only internal representativity within each group would be required and respective weighting according to national proportions of immigrant groups could be done using census and other survey information.

Perspectives

In summary, the results of this thesis suggest several perspectives for future research on immigrant health as such and specifically in relation to exposure to tobacco and its related morbidity and mortality. Two alternative study designs for future studies are proposed, which would vary depending on the breadth and the depth of the information sought, to better understand immigrant health and tobacco.

Our innovative protocol has been effective in conducting rapid and independent studies aimed at gathering information on tobacco use or other health behaviors in immigrants anonymity setting, the study could focus on a particular set of questions, e.g. actual tobacco use: the products used, the profile of the user (current daily, current occasional, former, never) and the intensity of use.

In this regard, the questionnaire could be modified based on the selected topic of interest, and assessed in a pilot study prior to a full implementation of the study.

The main asset of this type of methodology rests in its effectiveness for conducting rapid and independent field study gathering information on tobacco use in a target group of the population. As discussed earlier, such a study could include non-immigrants in its target group in order to allow for comparisons and to prevent potential bias. However, the inclusion of natives would require a drastic increase in sample size, in order to recruit the appropriate number of immigrants for comparison by country of origin and sex, unless immigrants are oversampled. Although resulting in a convenience sample it would still be informative for various migrant groups, which would be represented in the sample. tobacco use in all its forms, motivation to quit, cessation attempts, exposure to secondhand smoke, knowledge, perceptions and attitudes about the harmfulness of tobacco and the benefits of quitting tobacco use. A telephone-base survey would require an authorization from the CNIL, as it implies dialling individual numbers that could be used to identify the participant. This method has been extensively described [START_REF] Potthoff | Telephone sampling in epidemiologic research: to reap the benefits, avoid the pitfalls[END_REF] and is used routinely in France for the Health Barometer surveys series [START_REF] Beck | Increasing trends in smoking in France: mains results of the French Health Barometer, France[END_REF][START_REF] Beck | Baromètre cancer 2010[END_REF][START_REF] Guignard | La consommation de tabac en France en 2014: caractéristiques et évolutions récentes[END_REF]. Even though this method implies longer preparation for authorization and ethical handling of individual data, it would permit repeated contact with the responder, and therefore allow completion of the full questionnaire in several times, depending also on the responder's availability. Specialized survey companies have developed techniques to automatically dial telephone numberseither landline or mobile phone -which in combination with the telephone owning coverage in France (more than one telephone number by resident) it would theoretically give a chance to each person in France to be contacted. This method has a clear advantage on the potential to obtain a representative sample. Its second advantage is a lower cost of implementation, as interviewers' time is optimized with no travelling or long recruitment time in the venues. Even if trying to reach only first and second generation immigrants, as they represent about 20% of the French population, only five calling attempts should theoretically be needed to reach an immigrant. Additionally, the use of interpreters can be organized more easily, as only one by required language in needed at a time on the call centre, which is the technical platform where the interviewers connect to potential participants. This method could be planned to obtain stratified representative samples.

In summary, I recommend two options for future larger scale studies on tobacco use in immigrants in France depending on the quantity of information required: a small focused resource of information (e.g. tobacco products prevalence) could be rapidly gathered through a field face-to-face survey in a combination of geographical areas and type of venues; a comprehensive resource of information in a representative sample of immigrants and/or natives could be collected via non-anonymous telephone surveys.

Both methods give the potential for comparisons with the natives. These two methods can be an alternative to register-based studies in other European studies with adaptation to each country's specific legal and ethical conditions, allowing potentially for a European multi-centric study.

CONCLUSIONS

The landscape of European populations is increasingly changing; thus Europe has become a multicultural and multi-ethnic society. Alongside the positive effects of migration on European countries seen through the economic contribution of immigrants of working age, this change raises questions relating to the sustainability of European society's social models. In this vein, immigrant health represents a public health challenge to guarantee achievement of an individual's highest attainable health, equity and access to health care. Further, from an epidemiological point of view, research on immigrant health still publications from 5 EU countries [START_REF] Nielsen | Poorer self-perceived health among migrants and ethnic minorities versus the majority population in Europe: a systematic review[END_REF]. Nevertheless, the disadvantaged patterns for immigrants were clear. The TOBAMIG study presented in Chapter 2 has shown the feasibility to conduct a study on tobacco use in immigrants in France, provided modifications are done; the methodological remedies to address these points were discussed in the previous section (see above Recommendations). Despite its small sample size, the TOBAMIG study also observed a higher prevalence of smoking in immigrant men, as well as indication of a higher prevalence of waterpipe smoking. The use of smokeless tobacco was only observed in one respondent, but the reduced size of the pilot study do not allow for conclusions relating to this area.

In regard to cancer burden -whether morbidity or mortality -literature is less scarce on immigrants in European countries but very few have focused on outcomes relating to TRCs.

Our study on tobacco-related cancers incidence in Danish immigrants, presented in Chapter III, contributes to the gap in knowledge. We have shown that Danish immigrant men presented an overall lower risk of tobacco-related cancer incidence (SIR=0.85).

Nevertheless, we observed that this reduction of incidence varied greatly by country of origin of immigrants and to a lesser extent between the 1 st and 2 nd generations. Thus in any future study, it is important to remember that immigrants constitute heterogeneous groups with respect to their ethnic features, cultural roots, and health behaviours, and therefore separate analyses for different immigrant groups is indicated.

Other studies have demonstrated that most immigrants in Europe are disadvantaged in regard to health as compared to the majority population even after controlling for age, sex and socio-economic factors [START_REF] Nielsen | Poorer self-perceived health among migrants and ethnic minorities versus the majority population in Europe: a systematic review[END_REF]. Though, immigrants seem to bear a double burden with the negative impact on health of immigrant status and socioeconomic position.

Noticeably, a majority of studies on cancer in immigrants have been conducted in the Nordic countries, with the help of their registers -either population-based or cancerspecific registries.

  • d'identifier les limites des objectifs 1 et 2 et proposer un design d'étude pour mettre en oeuvre une étude à grande échelle sur l'usage du tabac et le risque de cancer chez les immigrés en France. Le Chapitre I comprend deux revues de littérature, la première sur le tabagisme et la seconde sur le fardeau des cancers liés au tabac chez les migrants en Europe. Par la suite, un aperçu global du phénomène de la migration, du tabagisme et des cancers liés au tabac est présenté comme arrière-plan de cette thèse. L'étude pilote TOBAMIG est présentée au chapitre II; un protocole innovant a été développé afin d'enquêter sur l'usage du tabac dans un échantillon français des immigrés non-européens, afin d'informer plus tard, la conception et la mise en oeuvre d'une étude à grande échelle sur l'usage du tabac et de ses déterminants dans la population immigrée en France. Dans le chapitre III, l'incidence des principaux cancers liés au tabac est explorée et comparée entre les natifs Danois et les 1 ères et 2 èmes générations d'immigrés, par région d'origine, à l'aide d'une étude de cohorte basée sur un registre contenant tous les hommes vivant au Danemark entre 1978 et 2010. La discussion générale (chapitre IV) résume les résultats de cette thèse avec ses forces et ses limites. Une réflexion critique et les perspectives de la recherche future -y compris des designs d'étude à grande échelle -sont présentées.

  CHAPTER I: INTRODUCTION ........................................................................................... 1 Overview .................................................................................................................. 2 Background: Literature review..................................................................................

  representative sample of the French immigrant population, which required the development of a questionnaire and of a specific methodology of sampling and recruiting the target population. The study protocol was submitted to the IARC Ethical committee (IEC) in April 2012. As the IEC was concerned with the potential of the study to provoke stigma or discrimination, the Committee suggested carrying out a pilot study in collaboration with Migrations Santé -a local non-profit organisation providing health promotion to migrants that I had previously identified and approached. In line with the IEC's comments, it was decided not to conduct the originally proposed larger scale study and the IEC's recommendation was to use a pilot study to inform future research. This change implied that the development and completion of the large scale study originally planned would not fit in a timely manner with the PhD program. It was decided to conduct a pilot study in order to test the study protocol, in particular the random selection of recruitment locations, and to develop, test and validate the questionnaire to ensure the acceptability of the survey. In this way the participation rate and the representativeness of the participating sample could also be tested.

Figure 1 . 1 :

 11 Figure 1.1: Inclusion and exclusion of publications in the systematic review on tobacco use in immigrants in Europe.

Figure 1 . 3 :

 13 Figure 1.3: Distribution of international migrants in the world in 2013, in number. Source: From International migration wallchart 2013, by United Nations, Department of Economic and Social Affairs, Population Division, © 2013 United Nations. Reprinted with the permission of the United Nations.

Figure 1 . 4 :

 14 Figure 1.4: Proportion (%) of international migrants in the European countries in 2014. Source: Eurostat

Figure 1 . 5 :

 15 Figure 1.5: Trends of the proportion of immigrants in the French metropolitan population between 1911 and 2012. Source: INSEE population censuses (www.insee.fr)

Figure 1 . 8 :

 18 Figure 1.8: Population attributable fraction (AFp) by tumor site for all tobacco-related cancers (TRC), based on smoking prevalence among cancer cases of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Source: From Agudo et al., 2012

Figure 1 . 9 :Figure 1 . 10 :

 19110 Figure 1.9: Estimated age-standardised lung cancer incidence rates worldwide in 2012 for men.Source: Globocan 2012 (IARC)[START_REF] Ferlay | GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase[END_REF]



  Smoking or smokeless tobacco use contributes to the development of cancer associated with tobacco use. Approximately 80% of lung cancer cases in Europe are attributed to cigarette smoking[START_REF] Agudo | Impact of cigarette smoking on cancer risk in the European prospective investigation into cancer and nutrition study[END_REF]. TRC incidence patterns, most prominent in lung cancer, may therefore reflect the extent to which immigrants use tobacco, which could suggest adoption of the lifestyle of the host population or continuation of behaviours typical of their country of origin, including use of tobacco. There are implications for cancer risk of immigrant women coming from low-prevalence tobacco use countries if they begin to smoke as often as the native European women. Incidence rates of TRC may therefore suggest relevant insight into patterns of smoking among immigrants, especially when there is a significant difference in TRC risk between the country of origin's population from which the migrants came and the host population[START_REF] Parkin | Studies of cancer in migrants: rationale and methodology[END_REF]. We expect patterns of TRC incidence in immigrants to be in line with patterns of tobacco use. That is, immigrants may use tobacco differently than the natives and this may result in tobacco-attributable disease risk dissimilar to those of natives in the host-country.The aims of this thesis were  Originally, to investigate tobacco use and determinants of use in immigrants in France. This objective was modified and evolved into developing and testing a study protocol and data-collection instrument to investigate tobacco use in immigrants in Lyon, including data collection which could generate preliminary estimates of tobacco use in a small number of immigrants surveyed in a pilot study. To compare the burden of TRC between immigrants and natives in Denmark. To put these results into context with current knowledge on tobacco use and TRC occurrence and mortality in migrant populations in Europe. To describe limitations of the studies and give guidance on how to set up a study on tobacco use and cancer risk in immigrants in France.Chapter I comprises two literature reviews, the first on the tobacco use and the second on the burden of the TRC in migrants in Europe. Subsequently, a global overview of the migration phenomenon, the tobacco use and the TRC were presented as a background to the thesis.The TOBAMIG feasibility study is presented in Chapter II; it developed an innovative protocol and explored the tobacco use in a French sample of non-European immigrants, in order to inform later the design and implementation of a large scale study on tobacco use and its determinants in the immigrant population of France. The TOBAMIG pilot study presented in Chapter II had for specific objectives: to design and evaluate an approach to identify a sample of the immigrant population in Lyon Metropole,  to ascertain the feasibility of conducting private interviews of the target population intercepted in public places,  to assess the participation to the study, and  to pilot the questionnaire on tobacco use developed for the survey.In Chapter III, major TRCs incidence were explored and compared between native Danes and 1 st and 2 nd generation immigrants by region of origin using a register-based cohort study involving all Danish men. The specific objective of the Danish cohort study, presented in Chapter III, was to compare the incidence of TRCs among male immigrants of first and second generation in Denmark with the incidence among native Dane males.

4 )

 4 to develop and pilot a questionnaire on tobacco use, determinants of use and other domains including knowledge of adverse effects of tobacco on health; and 5) to summarize tobacco use in immigrants contacted in the pilot study This Chapter presents the TOBAMIG feasibility study. The related scientific manuscript (submitted for peer-review on 24 th November 2015) is included below. The manuscript is

  number of interviews completed by type of venue and the total number of interviews completed in comparison to the a priori set sample size informed the discussion of logistics including determinants of completeness and possible remedial measures. The prevalence of tobacco users obtained by type of venue informed the possible presence or absence of a selection bias or independence of smoking profile from the sampling modality, a consideration impacting the validity of tobacco use estimates that could be derived from the sampling approach used in the pilot study. The time required to administer the study questionnaire and the level of completeness were examined in relation to the number of questions, location of questions in the instrument as well as by interviewer, suggesting changes in the instrument and level of training.

Figure 3 . 1 :

 31 Figure 3.1: Numbers of immigrants and their descendants (in thousands) by country of origin in Denmark, on 1 st January 2015. Source: From Statistical Yearbook 2015, Statistics Denmark (www.statbank.dk/folk1)

  attributable fraction as estimated by Agudo et al. (Agudo et al., 2012): laryngeal (C32), lung (C34), lower urinary tract (C65-68: pelvis, ureter, and bladder), oropharynx (C09-10; C12-14), esophagus (C15), oral cavity (C00-08), liver (C22), stomach (C16) and pancreatic cancers (C25). All of these cancers had a smoking attributable fraction above 20%, with the exception of pancreatic cancer. Pancreatic cancer was included because, together with oral and esophageal cancer, it is an established cancer site associated with smokeless tobacco (International Agency for Research on Cancer, 2012b, International Agency for Research on Cancer, 2007, Secretan et al., 2009b).

  in Denmark at lower or higher risk of tobacco-related cancers? A Danish nationwide cohort study S. Ducarroz, ME. Leon, AM. Schott, S. Friis, C. Johansen, J. Schüz Acta Oncologica, 2015; Early Online: 1-8

Option 2 -

 2 Household non-anonymous survey Alternatively, a household national telephone-based study could be developed to take advantage of the comprehensive questionnaire, which was developed based on previous validated questionnaires (Giovino et al., 2012, Beck and Gautier, 2012, Gallus et al., 2014, Oh et al., 2010, Simon and Clément, 2006), and covers a large set of information on

Table 2 .

 2 2.1 Tobacco use in immigrants in Europe ................................................................. 2.2 Tobacco-related cancers in migrants in Europe .................................................. 3 Rationale .................................................................................................................. 3.1 International migration ...................................................................................... Inclusion and exclusion of publications in the systematic review on tobacco use in immigrants in Europe. ...................................................................................... 24 Figure 1.2: Inclusion and exclusion of publications in the systematic review on tobacco related cancers in migrants in Europe. ....................................................................... 31 Figure 1.3: Distribution of international migrants in the world in 2013, in number..... 38 Figure 1.4: Proportion (%) of international migrants in the European countries in 2014. .................................................................................................................................. 39 1: Tobacco smoking profiles according to current and past smoking exposure. .................................................................................................................................. 65

3.2 Tobacco use ....................................................................................................... 3.3 Tobacco-related cancers ..................................................................................... 4 Hypotheses and objectives of the thesis ................................................................... CHAPTER II: TOBAMIG A FEASIBILITY STUDY................................................................. 1 Objective .................................................................................................................. 2 Background .............................................................................................................. 2.1 The French immigrant populations ..................................................................... 2.2 French immigrants' health .................................................................................. 2.3 Tobacco use behaviour in France ........................................................................ 3 Methods of the pilot study ....................................................................................... 3.1 Population groups .............................................................................................. 3.2 Sampling approach ............................................................................................. 3.3 Questionnaire development ............................................................................... 3.4 Evaluation .......................................................................................................... 4 Overall and additional results ................................................................................... ARTICLE 1 ......................................................................................................................... CHAPTER III: TOBACCO-RELATED CANCERS IN AN IMMIGRATION PERSPECTIVE ........ 1 Objective ................................................................................................................ 2 Background ............................................................................................................ 3 Methods of the cohort study .................................................................................. 3.1 Population groups ............................................................................................ 3.2 Cancer codes ....................................................................................................

Figures Figure 1.

1: Figure 1.5: Trends of the proportion of immigrants in the French metropolitan population between 1911 and 2012. .......................................................................... 40 Figure 1.6: Trends of the proportion of 1 st and 2 nd generation immigrants in the Danish population between 1980 and 2015. .......................................................................... 41 Figure 1.7: Current tobacco smoking prevalence by country income-level and sex, 2007-2013. ................................................................................................................. 43 Figure 1.8: Population attributable fraction (AFp) by tumor site for all tobacco-related cancers (TRC), based on smoking prevalence among cancer cases of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. ............................ 46 Figure 1.9: Estimated age-standardised lung cancer incidence rates worldwide in 2012 for men. ..................................................................................................................... 47 Figure 1.10: Estimated age-standardised lung cancer incidence rates worldwide in 2012 for women......................................................................................................... 47 Figure 2.1 Trends of immigration rates by nationality in France from 1851 to 2008. .. 56 Figure 2.2: Distribution of 1 st and 2 nd generation immigrants and natives by region in France. ....................................................................................................................... 57 Figure 3.1: Numbers of immigrants and their descendants (in thousands) by country of origin in Denmark, on 1 st January 2015. ................................................................... 103 Tables

Table 2 .

 2 2: Characteristics of interviews by type of venue for the 2 main interviewers 66

Table 3 .

 3 1: Distribution of country or region of birth in 1 st generation immigrants with or without date of immigration in Denmark in 1978 to 2010 .................................... 106

Table 3 .

 3 2: Distribution of tobacco-related cancers in 1 st generation immigrants with or without date of immigration in Denmark in 1978 to 2010 ........................................ 107

Table 3 .

 3

3: Tobacco-related cancers overall and lung cancers SIR by immigration status and region of birth in Danish men in 1978 to 2010 ................................................... 109 Table 3.4: Other tobacco-related cancers SIR by immigration status and region of birth in Danish men in 1978 to 2010 ................................................................................. 110 Appendices Appendix 1: Comparable prevalence estimates for tobacco smoking 2013 ............... 171 Appendix 2: TOBAMIG questionnaire ....................................................................... 175

  , McDonald and Kennedy, 2004, Rubalcava et al., 2008). Nevertheless, studies (Jayaweera and Quigley, 2010) have challenged the use of linear acculturation models (Abraido-Lanza et al., 2006) and highlighted the importance of taking into account the complexity of social determinants, health behaviour and disease patterns in countries of origin, and the pre-migration health status, in understanding patterns of migrants' health over time. Acculturation was first defined as "the phenomena which results when groups of individuals having different cultures come into continuous first hand contact with subsequent changes in the original cultural patterns of either or both groups" (Redfield et al., 1936).

2 BACKGROUND: LITERATURE REVIEW

2.1 Tobacco use in immigrants in Europe

Interventions to prevent tobacco use directed at the general population may be less effective in immigrants if their tobacco use differ from those of the general population, but there is currently limited supporting evidence available for most European countries, especially France and, to a lesser extent, Denmark.

In 2004/2005, the Survey of Health, Aging and Retirement in Europe (SHARE) examined health differences between immigrants and the native-born populations aged 50 years and older in 11 European countries (Sole-Auro et al., 2012, Sole-Auro and Crimmins, 2008). In this study, differences in smoking behaviours were observed between immigrants and nonimmigrants. Immigrants in Denmark and France exhibited a 13% and 31% higher likelihood of being current smokers compared to non-immigrants respectively, however, when pooled together smoking behaviour across the 11 countries did not differ significantly between immigrants and the native-born (Sole-Auro and Crimmins, 2008).

  Europe, the immigrant population in 2014 was recorded at more than 51 million in all the MeSH terms and keywords as displayed in Figure1.2. The 910 papers retrieved were filtered first on title (150 articles remained) and then by abstract (90 articles remained) following the inclusion and exclusion criteria listed below. Finally, the full-texts of the remaining articles were assessed and 60 articles retained in the review. All peer-reviewed original studies in English or French language published after 1990 were included. Studies were included if they met the following conditions: international migration to a European country was reported and the focus was on cancer overall or one of the 8 main TRC(Agudo et al., 2012): lung, larynx, oropharynx, oesophagus, oral cavity, liver, stomach and lower urinary tract (bladder) cancers. Studies were excluded if they concentrated on a non-European host country; if they focused on other diseases (including other cancers) or on risk factors; if they were not original research, e.g. review, letter,

	EU Member States (European Commission, 2014). Literature on cancer risk of immigrants,
	especially for tobacco exposure, in Europe in general is scarce. However, a body of work
	focused on cancer in immigrants exists but this is predominant based on work in the Nordic
	countries and in the United Kingdom. Although in these countries immigrants do not
	represent a large proportion of the population in comparison to other EU countries, they
	have pioneered work in this field, largely facilitated by their population and cancer registries.
	The Swedish immigrant study showed that the overall cancer pattern in immigrants was set
	before the age of 20 years, as a large proportion of the current immigrant population in
	Sweden had entered the country in their early 20s. That is, they found that immigrants to
	Sweden who lived in a low-risk country to the age of 20 remained at low risk, and conversely
	those who lived to this age in a high-risk country remained at high-risk (Hemminki et al.,
	2014).
	In 2010, the cancer risk in non-western migrants in Europe was assessed (Arnold et al., 2010)
	and it was found that more favourable all-cancer morbidity and mortality were observed in
	immigrants in comparison to the natives of their host-countries. Still, large geographically-
	specific disparities existed: non-western migrants were more likely to suffer from cancers
	related to exposure to infections in their early life. Additionally, lower incidence and/or
	mortality of lung cancer were observed for migrant women from most origins, with the
	exception of Northern African and South Eastern Asian migrant women in France. For men, a

different pattern was observed in the different host countries with a higher incidence and/or mortality of lung cancer for Eastern and Southern European (including Turkey) migrants. This study discussed the potential role of diet, physical activity, reproductive factors or socioeconomic status in the observed patterns of cancer in non-western migrants but did not address the possible role tobacco use exposure might have played. However, it is known that smoking patterns can vary greatly in immigrants when compared to the native populations of the European host countries. This led to the further investigation of previous work analysing TRCs in immigrant populations.

Literature search strategy

A literature review conducted to identify the published research addressing TRC in migrants in Europe. I designed a search in September 2015 using PubMed with a combination of editorial, news; if they were published before 1990 or in another language than English or French; if the focus was on intra-national migration (rural to urban), perception and communication or methodology issues; and finally, if TRC or migration was only a side issue

  Thirteen studies investigated the overall cancer or specific TRC burden in immigrants in Nordic and/or Baltic countries moving to Sweden[START_REF] Abdoli | Cancer mortality by country of birth, sex, and socioeconomic position in Sweden, 1961-2009[END_REF][START_REF] Nilsson | Cancer survival in Estonian migrants to Sweden[END_REF], Nilsson et al., 1993, Hemminki et al., 2010b, Hemminki et al., 2010a, Hemminki and Li, 2002a, Hemminki and Li, 2002b, Hemminki et al., 2002, Mousavi et al., 2012c, Mousavi et al., 2012a, Mousavi et al., 2011, Mousavi et al., 2010b, Rostila and Fritzell, 2014). A higher mortality from all cancers was observed in women from Denmark (SIR 1.27, p<0.05), as well as in men from Denmark and Finland (Rostila and Fritzell, 2014). Similarly, Abdoli et al. Specifically related to TRCs, lower rates of individual TRC were found in East African and West African immigrants in England and Wales (Standardized Mortality Ratio 17-62, p<0.05) (Wild and McKeigue, 1997). Lower incidence rates for most TRCs were also observed in Moroccan and North African immigrants in the Netherlands (SIR 0.1-0.7, p<0.05) (Visser and van Leeuwen, 2007). Higher incidence or mortality of liver cancer was found in Moroccan immigrants in the Netherlands (Visser and van Leeuwen, 2007), in Sub-Saharan immigrant men and women in Sweden (Hemminki et al., 2010b), in West African immigrant men in England and Wales (Grulich et al., 1992), in West African immigrants in France (Bouchardy et al., 1995), in men born in the African Commonwealth (except East Africa) in England and

	Nordic and Baltic countries immigrants

an overall lower cancer mortality than corresponding natives (Mortality Risk Ratio (MRR) ranging from 0.65-0.71 in men and 0.49-0.83 in women, p<0.05)

[START_REF] Spallek | Cancer mortality patterns among Turkish immigrants in four European countries and in Turkey[END_REF][START_REF] Zeeb | Transition in cancer patterns among Turks residing in Germany[END_REF][START_REF] Rostila | Mortality differentials by immigrant groups in Sweden: the contribution of socioeconomic position[END_REF]

. In contrast to the lower overall mortality reported, Zeeb et al. also showed an increase in lung cancer mortality in Turkish immigrant men in Germany

[START_REF] Zeeb | Transition in cancer patterns among Turks residing in Germany[END_REF]

. However, in France and the Netherlands, the lung cancer mortality rate was lower (MRR 0.81 and 0.83, p<0.05)

[START_REF] Spallek | Cancer mortality patterns among Turkish immigrants in four European countries and in Turkey[END_REF]

.

Among the 8 studies investigating cancer incidence in Turkish immigrants, 4 focused on specific cancer-sites: breast, cervical, colorectal, gallbladder, liver, lung, oesophageal, prostate and/or stomach cancers

(Hemminki et al., 2010b, Mousavi et al., 2012a, Arnold et al., 2013a, Arnold et al., 2013b)

. All-site cancer incidence in Turkish immigrants was lower compared to their corresponding host-countries natives, for both sexes

(Visser and van Leeuwen, 2007, Mousavi et al., 2013)

. Visser et al. observed a 34% lower all-cancer incidence (SIR 0.66, p<0.05) in Turkish immigrants

[START_REF] Visser | Cancer risk in first generation migrants in North-Holland/Flevoland, The Netherlands, 1995-2004[END_REF]

. The lung cancer incidence rate was higher in Turkish men than their native counterparts

[START_REF] Spallek | Cancer incidence rate ratios of Turkish immigrants in Hamburg, Germany: A registry based study[END_REF][START_REF] Zeeb | Transition in cancer patterns among Turks residing in Germany[END_REF][START_REF] Mousavi | Cancer incidence among Turkish, Chilean, and North African first-generation immigrants in Sweden compared with residents in the countries of origin and native Swedes[END_REF]

. Additionally, while Mousavi et al. observed a higher lung cancer incidence in Turkish immigrants to Sweden than natives but a similar incidence to men in Turkey, they found that Turkish immigrant women had higher lung cancer incidence than women in Turkey but similar to that of native Swedish women, which could indicate the presence of an influencing lifestyle factor

[START_REF] Mousavi | Cancer incidence among Turkish, Chilean, and North African first-generation immigrants in Sweden compared with residents in the countries of origin and native Swedes[END_REF]

. Higher liver cancer incidence was also observed in Turkish immigrants in Sweden (Standardized Incidence Ratio (SIR) of 2.15)

(Hemminki et al., 2010b)

and in the Netherlands (SIR 4.6) (Visser and van Leeuwen, 2007).

showed higher cancer mortality in women born in Denmark and Iceland compared to that of women born in Sweden

[START_REF] Abdoli | Cancer mortality by country of birth, sex, and socioeconomic position in Sweden, 1961-2009[END_REF]

. A higher incidence of all cancers was observed in Danish immigrants (SIR 1.07, p<0.05), while it was lower in Finnish immigrants and their descendants (SIR 0.88-0.92, p<0.05), and in Norwegian immigrants (SIR 0.87, p<0.05)

(Hemminki and Li, 2002a)

. Several studies observed lower bladder cancer incidence in Finnish immigrants for both sexes

(Hemminki et al., 2010a, Mousavi et al., 2010b, Hemminki and Li, 2002b, Hemminki and Li, 2002a)

. However, Hemminki et al. observed lower bladder cancer incidence in women only, while in men there was an increased bladder cancer incidence

(Hemminki et al., 2002)

. Higher lung cancer incidence in immigrants from the Nordic countries residing in Sweden was observed in several studies

[START_REF] Mousavi | Esophageal cancer risk among immigrants in Sweden[END_REF], Hemminki and Li, 2002a, Mousavi et al., 2010b)

, while a lower incidence of lung cancer was shown in immigrant men from Baltic countries

[START_REF] Mousavi | Esophageal cancer risk among immigrants in Sweden[END_REF]

.

North African, Sub-Saharan and other African immigrants

Fifteen studies investigated the risk of cancer in African immigrants living in Europe, 9 of which also documented cancer mortality. Most of the studies found lower cancer mortality overall in African immigrants

[START_REF] Bouchardy | Cancer mortality among sub-Saharan African migrants in France[END_REF][START_REF] Bouchardy | Cancer mortality among north African migrants in France[END_REF][START_REF] Grulich | Cancer mortality in African and Caribbean migrants to England and Wales[END_REF][START_REF] Khlat | Cancer in Mediterranean migrants--based on studies in France and Australia[END_REF][START_REF] Visser | Cancer risk in first generation migrants in North-Holland/Flevoland, The Netherlands, 1995-2004[END_REF][START_REF] Norredam | Cancer incidence among 1st generation migrants compared to native Danes--a retrospective cohort study[END_REF]

living in Denmark, England and Wales, France and the Netherlands. However, higher overall cancer mortality was observed in Sub-Sahara African immigrants in Denmark

[START_REF] Norredam | Inequalities in mortality among refugees and immigrants compared to native Danes--a historical prospective cohort study[END_REF]

, in West African males in England and Wales

[START_REF] Grulich | Cancer mortality in African and Caribbean migrants to England and Wales[END_REF]

, and in men from Angola in Sweden

[START_REF] Abdoli | Cancer mortality by country of birth, sex, and socioeconomic position in Sweden, 1961-2009[END_REF]

.

  [START_REF] Abdoli | Cancer mortality by country of birth, sex, and socioeconomic position in Sweden, 1961-2009[END_REF], and in South Asian immigrants[START_REF] Wild | Cross sectional analysis of mortality by country of birth in England and Wales, 1970-92[END_REF][START_REF] Winter | Cancer incidence in the south Asian population of England (1990-92)[END_REF][START_REF] Mangtani | Cancer mortality in ethnic South Asian migrants in England and Wales (1993-2003): patterns in the overall population and in first and subsequent generations[END_REF], in Bangladeshi, Pakistani and Indian immigrants[START_REF] Balarajan | Ethnicity and variations in the nation's health[END_REF][START_REF] Swerdlow | Cancer mortality in Indian and British ethnic immigrants from the Indian subcontinent to England and Wales[END_REF], and in Asian Arab immigrant women(Mousavi et al., 2012c). Higher lung cancer mortality or incidence was observed in South East

, higher oral cavity cancer mortality in West and East African immigrant men and women in England

[START_REF] Grulich | Cancer mortality in African and Caribbean migrants to England and Wales[END_REF]

, higher pharynx cancer in East African immigrant men and higher cancer of the oesophagus in East African women in England

[START_REF] Grulich | Cancer mortality in African and Caribbean migrants to England and Wales[END_REF]

were observed.

South, Southeast, other Asian, and Middle East immigrants

Twenty six studies investigated the burden of cancer and TRC in South, Southeast, other Asian, and Middle East immigrants in Europe. Lower mortality and incidence of all cancers was observed consistently in the studies in England and Wales, Sweden, Denmark and Spain for immigrants from Asia, South Asia, Bangladesh, Pakistan, India, Middle East, Iran and Iraq (Norredam et al., 2007, Norredam et al., 2012, Harding and Rosato, 1999, Mousavi et al., 2010a, Maringe et al., 2013, Winter et al., 1999, Rastogi et al., 2008, Mangtani et al., 2010, Regidor et al., 2008, Rostila and Fritzell, 2014, Harding, 2003). Yet, Abdoli et al. observed a higher mortality for all cancers in immigrants from Laos and Cambodia in Sweden (Abdoli et al., 2014). Compared to the respective host-country natives, lung cancer incidence and mortality were lower in South East Asian immigrant (Hemminki et al., 2010a, Bouchardy et al., 1994), in Iranian men (Mousavi et al., 2012a, Mousavi et al., 2010b, Mousavi et al., 2010a), in Asian women -in particular in Indian women (SIR 0.16, p<0.05) (Mousavi et al., 2012a), in Asian immigrant women (Asian women in France (Bouchardy et al., 1994) and in Asian Arab immigrant men in Sweden (Mousavi et al., 2012a). Higher liver cancer incidence and mortality was observed in immigrants from Asia and Middle East in most studies (Visser and van Leeuwen, 2007, Bouchardy et al., 1994, Hemminki et al., 2010b, Haworth et al., 1999, Winter et al., 1999, Mangtani et al., 2010). However, lower liver cancer incidence was shown in Iranian immigrant men and women in Sweden (Mousavi et al., 2010a). Other studies described higher oral cancer incidence in Asian immigrants (Warnakulasuriya et al., 1999), higher stomach cancer mortality in Asian immigrants (Bouchardy et al., 1994, Abdoli et al., 2014), lower stomach incidence in Iranian immigrants (Mousavi et al., 2010a), lower bladder cancer incidence in South East Asian immigrants (Hemminki et al., 2010a, Mousavi et al., 2010b, Winter et al., 1999), higher bladder cancer incidence in Arab immigrants (Hemminki et al., 2010a) and Iranian immigrant men (Mousavi et al., 2010a), and higher oral cavity cancer in South Asian immigrants (Mangtani et al., 2010, Swerdlow et al., 1995).

  United Nations, 2013). In 2013, the most common migration pattern (40%) (International Office for Migration, 2013) was from countries of the South to countries of the North, using the North-South categorization as defined by the United Nations Development Program (UNDP). UNDP's "South" includes countries ranking low, middle and high on the

	Human Development Index (HDI) developed by the United Nations Development
	Programme (http://hdr.undp.org/en/content/human-development-index-hdi); "North"
	includes countries ranking very high on the HDI. In 2013, Europe had the largest number of
	migrants (72 million). The proportion of men and women is nearly equal among migrants
	globally: in 2013, women accounted for 48% of the international migrants, but were more
	numerous in the developed regions, the highest percentage being in Europe with 51.9%

3 times less numerous (75 million in 1965) but constituted already 2.3% of the world population ((United Nations, 2013). Globally, a large majority of migrants (74%) were of working age in 2013, i.e. between the ages of 20 and 64. Furthermore, migrants were on average older than the global population (median age of 38.4 years and 29.2 years in 2013, respectively), and 70% of all of the migrants aged 65 and over were concentrated in the developed regions.

Trends of the proportion of 1 st and 2 nd generation immigrants in the Danish population between 1980 and 2015.

  The 2 nd generation immigrants are the direct descendants of immigrants -following the conventional French definition. In 2008, 6.7 million -or 11% of the population -were 2 nd generation immigrants, including 2.2 million below 18 year of age.In the 25-54 age group (which is used for comparison with other European countries), France was in 2008 the country with the largest proportion of 2 nd generation immigrants (13.5%) Within one and a half century after Columbus's finding of Nicotina tobacum in the Americas and its introduction into Europe, tobacco was being used around the globe. Tobacco leaves were first used in the form of pipes, cigars and snuff but its use spread massively from the end of the 19 th century with the rise of manufactured cigarettes. At the beginning of the in contrast to 17% in high-income countries. This gender gap in smoking prevalence was observed, among others, in the main countries of origin of French and Danes non-western migrants: Algeria (28% vs. 2%), Morocco (43.6% vs. 1.6%) and Turkey (41.6% vs. 13.2%) (World Health Organisation, 2013).

	3.2 Tobacco use
	(INSEE, 2012b). Similarly, the proportion of 1 st and 2 nd generation immigrants in France was
	over one quarter of the total population aged 25-54 (26.2%), the highest in Europe 2000s, about 30% of adults all over the world, including an increasing number of women,
	(European Commission, 2011). used tobacco (Amercian Cancer Society, 2015).
	Tobacco is used in either the smoking or the smokeless forms (Amercian Cancer Society,
	Denmark 2015), each including different type of products. Globally, manufactured cigarettes are by far
	In Denmark, immigrants are defined -following the most commonly used definition -as the most commonly used type of tobacco product, followed by roll-your-own cigarettes,
	those born abroad. The proportion of immigrants and their descendants in Denmark has
	increased (see Figure 1.6) from around 3.1% in 1980 to 13.1% of the total Danish population
	in January 2015, corresponding to 657,473 persons (Statistics Denmark, 2015). Nearly 10%
	are 1 st generation immigrants and 3.1% are 2 nd generation immigrants.
	14%
	13%
	12%
	11%
	9% 10% Figure 1.
	8%
	7%
	6%
	5%
	4%
	3%
	2%
	1%
	0% Cigarette smoking
	1980 Globally, more than 1.1 billion adults -950 million men and 177 million women -or 21% of 1985 1990 1995 2000 2005 2010 2015
	the world population were current cigarette smokers in 2013 (World Health Organisation, Figure 1.6: Source: Statistics Denmark (http://www.statbank.dk/) 2015). The prevalence of smoking was the highest in high-income countries between 2007

cigars and pipes. In the Mediterranean region, as well as North Africa and parts of Asia, waterpipes -also known as shisha or narghile -are traditionally smoked. Over 300 million people around the world, the vast majority of whom live in South Asia, use smokeless tobacco products (Amercian Cancer Society, 2015). Smokeless tobacco consists essentially of chewing tobacco that is place in the mouth, in the inner cheek or inner lip and chewed or sucked, as well as moist snuff and dry snuff -a fine tobacco powder that is inhaled through the nose or taken by the mouth. Snus is a form of snuff that is mainly used in the European Nordic countries; it is taken as a pinch or in sachets placed under the lip for extended periods (Amercian Cancer Society, 2015, World Health Organisation, 2015, International Agency for Research on Cancer, 2012b).

The prevalence of smoking reported by the Eurobarometer from its most recent survey in 2014 in men and women were respectively 31% and 22% in EU-28 and 34% and 29% in France, and 23% in Denmark in each sex (European Commission, 2015a, European Commission, 2015b). and 2013 (see

Figure 1.7)

. This difference in tobacco smoking prevalence between high-and middle-and low-income countries was mainly driven in 2013 by divergent smoking prevalence in women across countries, with only 3% of women being current smokers in low-income

7: Current tobacco smoking prevalence by country income-level and sex, 2007- 2013.

  Globally, more than 300 million people in at least 70 countries were using smokeless tobacco products in 2013, most of whom living in South East Asia (89%) and Africa, but also in Sweden and Norway (National Cancer Institute and Centers for Disease Control and Prevention, 2014). Generally, the prevalence of smokeless tobacco use is higher in men than in women but in some low-and middle-income countries a similar or higher prevalence has been observed in women, e.g. in Bangladesh (National Cancer Institute and Centers for Disease Control and Prevention, 2014). The prevalence of smokeless tobacco users in 13 to 15 years adolescents is also high in the South East Asia region -e.g. in Bhutan (9.4%), in India (9.0%), in Sri Lanka (6.8%) and in Myanmar (6.5%) -and is similar to the prevalence of cigarette smoking in the region (National Cancer Institute and Centers for Disease Control and Prevention, 2014). The largest increase in prevalence of ever trying since 2012 was observed in Sweden which rose by 11%, as well as in Spain and France (both rising by 5%). Within the EU, in addition to Sweden, an increase in smokeless tobacco prevalence was only observed in Hungary and Finland, both by 1%.

	Smokeless tobacco use 2015a). In 2014, smokeless tobacco was tried by 5% of the EU-28 countries population, including 4%
	who tried it only once or twice (European Commission, 2015a). Five EU-28 countries
	reported 10% of their population or a higher proportion having tried smokeless tobacco:
	40 Sweden (50%), Finland (14%), Denmark (13%), Austria (10%) and Estonia (10%). Current or
	35 past regular smokeless tobacco use prevalence is significantly higher in Sweden (15%) and in
	Norway (14%) compared to any other European countries, where it is virtually null (World 30 Health Organisation, 2015).
	25
	20	Total
	Lebanon in 2011, the prevalence of waterpipe smoking in 13-15 years old responders in 0 5 10 Men 15 Global High-income countries Middle-income countries Low-income countries Women Tobacco The waterpipe smoking prevalence in EU-28 countries remained stable in 2014 with 16% of
	Lebanon was 35%, much higher than the prevalence of cigarette smoking (around 11%) people reporting having tried a waterpipe, including 11% who tried it only once or twice
	(Maziak et al., 2015). High prevalence of waterpipe smoking in persons aged 15 years and (European Commission, 2015a). Notably, waterpipe smoking was more common in people
	above was also observed in Latvia, Lithuania, Cyprus, Denmark and Czech Republic (Maziak ages 15-24 (33%). The highest prevalence of ever trying waterpipe smoking was observed in
	et al., 2015), ranging from approximately 11.8% to 8%. Latvia (39%), Lithuania (34%), Denmark (34%) and Sweden (33%) (European Commission,

Source: WHO report on the global tobacco epidemic, 2015

Waterpipe smoking

Water pipes are most commonly used in India, Africa, and the Middle East (Amercian Cancer Society, 2015). Waterpipe smoking has become a global phenomenon among youth, and particularly in the Middle East, where waterpipe smoking was found to be more common than cigarette smoking in 13-15 years old adolescents

[START_REF] Maziak | The global epidemiology of waterpipe smoking[END_REF]

. For instance, in use in Europe

In 2014, the overall proportion of smokers in the EU countries was just over a quarter of the population (26%) (European Commission, 2015a). The highest prevalence of current smokers was observed in Southern Europe, in particular in Greece (38%), Bulgaria (35%), Croatia (33%) and France (32%). Two countries had less than 20% current smokers in their populations: Sweden (11%) and Finland (19%) (European Commission, 2015a). Since 2006, a decrease in smoking prevalence has been observed in most EU-28 countries. For all EU-28 countries, the prevalence of current smokers decreased from 32% in 2006 to 26% in 2014 (European Commission, 2015a). The countries that recorded the most significant decrease during this period were Estonia (from 33% to 22%), United Kingdom (from 33% to 22%), Italy (from 31% to 21%) and Denmark (from 32% to 23%). On the other hand, in Slovenia an increase in smoking prevalence was observed during the same period from 23% to 30%.

2: Distribution of 1 st and 2 nd generation immigrants and natives by region in France.

  The distribution by country of birth has not only been influenced by recent migration but also by historical migration flows.The age structure of the foreign-born population compared to the native-born shows that the migrant population is younger than the natives, and that young working-age adults represent a greater proportion in immigrants.Unlike international comparisons including all foreign-born persons, the French statistics use the narrower definition for an immigrant as recommended by the French High Council for Integration (HCI, http://hci.gouv.fr ), i.e. a person born abroad of a foreign nationality at birth. This therefore includes people born abroad, whether they acquired French nationality later on or remained foreigners. It does not include those born in France of foreign nationality (about 550,000) nor does it include the persons born abroad but of French nationality at birth. In 2011, there were approximately 1.8 million individuals born abroad with French citizenship, mainly in Maghreb (INSEE, 2012b). The migration phenomenon in France has been regularly described by the French national institute for statistics INSEE (INSEE, 2014, INSEE, 2012b, Tavan et al., 2005). Italy and Portugal died or returned to their country of birth, and fewer immigrants came to France from these countries (INSEE 2012b). During the same period, the proportion of immigrants coming from African and Asian countries increased significantly. In 2011, 43% of immigrants in France (2.4 million persons) were born in an African country. Immigrants born in the The geographic distribution of immigrants varies greatly in France; 2010 figures show the 1 st generation were mainly resident in metropolitan areas with the largest proportion of nearly 40% living in or near Paris in the Ile-de-France region and with the rest spread across the other regions of France (See Figure 2.2). To a lesser extent this urban

	2012b). Overall, in Lyon Metropole, the proportion of 1 st generation immigrants was
	above the national average with 13.9% in 2009, with an approximately equal number of
	men and women. First generation immigrants originating from African, European and
	Asian countries represented 50.8%, 30.1% and 15.4% of the total immigrant population
	distribution is also seen in the 2 nd generation immigrants. Despite limitations derived of Lyon Metropole respectively. Among non-European countries of origin, Algeria was
	from the actual small number of immigrants for the different origins, data on the the most represented with 24.7% of first generation immigrants, followed by Tunisia
	distribution of 1 st generation immigrants by municipalities are available from yearly (8.2%), Morocco (7.2%) and Turkey (3.4%) (INSEE, 2012c).
	censuses, with stratification by country of birth, sex and other required variables (i.e.
	http://www.reseau-quetelet.cnrs.fr ). As the 2 nd generation immigrant status is not recorded routinely in the census or as part of any other longitudinal studies, the only 2.2 French immigrants' health
	national estimates available for this population group are derived from one-off, cross-
	sectional studies (Beauchemin et al., 2010) and only a few include working-age groups
	(INSEE, 2012a). Therefore, no data were available on the demographic characteristics of
	the 2 nd generation immigrant population residing in the sampling area of Lyon
	Metropole.
	100%
	90%
	70% 80%	Other regions
	60% 50%	Paca, Languedoc-Roussillon
	countries (European Commission, 2014). In 2011 there were approximately 6.6 million 40% Rhone-Alpes, 30% Auvergne
	20% 2 nd generation immigrants in France, accounting for 10.4% of the population (INSEE, Ile-de-France 10% 2012a). The countries of origin of the 2 nd generation immigrants are related to the time of the different migration waves. In 2011, 3.2 million descendants of immigrants (48.1%) 0% 1st generation 2nd generation Natives 1995, Bouchardy et al., 1996). Bouchardy et al. (1996) investigated cancer mortality in
	had a parent that emigrated from a European country. New migration flows from Eastern immigrants immigrants immigrants from China, Italy, North Africa, Southeast Asian countries and Sub-Saharan
	Maghreb represent 30% of all immigrants in 2011; this proportion has remained stable Europe were too recent to have a significant impact on the descendants of immigrants. Also, 4 out of 10 descendants of immigrants had a father or mother born in the African countries in France between 1979 and 1985. These studies found lower cancer mortality Figure 2.Source: INSEE, enquête emploi 2006-2010 (http://www.insee.fr) in immigrants in France with respect to French natives. More recent studies have
	since 1975 (INSEE 2012b). Immigration from sub-Saharan Africa has been recorded more continent. In 2011, the main countries of origin of the 2 nd generation immigrants in investigated other diseases or health conditions in immigrants, i.e. tuberculosis (Che and
	recently, particularly from countries formerly under French administration. Immigrants France were Algeria (15.0%), Italy (13.6%), Morocco (10.9%), Portugal (9.2%), Spain The metropolitan region of Lyon, so-called Lyon Metropole, consisting of 59 Antoine, 2009), HIV infection (Jasseron et al., 2008, Lapostolle et al., 2011), and risk of
	(8.4%), Turkey (4.0%) and Tunisia (3.8%) (INSEE, 2012b). municipalities representing 1,281,971 inhabitants, was selected to implement the
	feasibility study because immigrants are more concentrated in larger urban areas (INSEE,

million) of the immigrant (foreign-born) population amongst the European countries, after Germany (9.8 million), and the United Kingdom (8.0 million) (European Commission, 2014). Throughout French history, different waves of immigrants have progressively contributed to the current group of 5.7 million immigrants -using the HCI definition -in 2012 (INSEE, 2015). Migration in France is not a new phenomenon.

Figure 2.1 shows the flux of immigrants coming from neighbouring countries in the nineteenth century -Belgium, England, Germany and Switzerland. In the twentieth century, after the First World War, immigrants arrived from Poland, Italy, and Spain. After the Second World War, immigrants came from Portugal and North Africa and more recently, from sub-Saharan Africa and Asia. The proportion of immigrants from European countries decreased from 66% in 1975 to 37% in 2011, as early immigrants from Spain, from Asia represented 14% of the pool in 2011. Apart from Cambodia, Laos and Vietnam, immigration from Asian countries has increased, especially from Turkey and China (INSEE 2012b).

Figure 2.1 Trends of immigration rates by nationality in France from 1851 to 2008. Source: From Immigrés et descendants d'immigrés en France. INSEE, Edition 2012, Paris. (INSEE 2012b)

Although the proportion of 1 st generation immigrants in France is close to the average in Europe, the proportion of 2 nd generation immigrants is remarkable: they are the most numerous by both proportion and number in comparison to the other European Few surveys or epidemiologic studies have been conducted to document health and nutritional status, or social or cultural conditions of specific immigrants' sub-groups in France

[START_REF] Conde | A socio-economic survey of Malian, Mauritanian and Senegalese immigrants resident in France[END_REF][START_REF] Darmon | An overview of the health status of migrants in France, in relation to their dietary practices[END_REF][START_REF] Khlat | Cancer in Mediterranean migrants--based on studies in France and Australia[END_REF][START_REF] Mejean | Diet quality of North African migrants in France partly explains their lower prevalence of diet-related chronic conditions relative to their native French peers[END_REF][START_REF] Beauchemin | Trajectories and Origins[END_REF][START_REF] Berchet | Health status of first-and second-generation migrants in France[END_REF]

. In the south of France, the Regional Observatory of Health conducted a survey in 2002 on elderly immigrants living alone

[START_REF] Siera Antelo | Conditions de vie et état de santé des immigrés isolés de 50 ans et plus en Lanquedoc-Roussillon[END_REF]

. Vaillant and Wolff investigated self-reported health among older immigrants and found that male immigrants from southern Africa and Asia, and female immigrants from northern Europe, southern Africa and Asia, are more likely to be in good health, while the health status is lower among immigrants from Eastern Europe living in France

[START_REF] Vaillant | Origin differences in self-reported health among older migrants living in France[END_REF]

. Several population-based, anthropological and sociocultural studies were conducted in the Rhône-Alpes region

[START_REF] Dumolard | Migration and demographic developments, Rhone-Alpes, 1954-1975[END_REF][START_REF] Begag | The social effects of the immigrants' spacial mobility[END_REF][START_REF] Békaert | Psychopathology of poly-addictions in children of Northern African immigrants[END_REF]

. To our knowledge, only very few epidemiologic studies have been conducted documenting cancer experience or determinants of cancer in immigrant populations in France

(Wanner et al., 1995a[START_REF] Bouchardy | Cancer mortality among Chinese and South-East Asian migrants in France[END_REF]

preterm birth

[START_REF] Zeitlin | Neighbourhood socio-economic characteristics and the risk of preterm birth for migrant and non-migrant women: a study in a French district[END_REF]

.

  years, the French National Institute for Prevention and Health Education (INPES) has run regular "Health Barometer" surveys on health behaviourincluding smoking -and risk perception of persons residing in France[START_REF] Beck | Increasing trends in smoking in France: mains results of the French Health Barometer, France[END_REF], maintained in 2014: that is the less educated, the lowest income and the unemployed smoke more[START_REF] Guignard | Le tabagisme en France: analyse de l'enquête Baromètre santé[END_REF][START_REF] Guignard | La consommation de tabac en France en 2014: caractéristiques et évolutions récentes[END_REF]. available on other forms of tobacco use or on determinants of use of tobacco in the immigrant population in France that was constituted of 5.7 million 1 st generation immigrants in 2012.

	In 2014, 29.0% of the 15-75 year-old regular smokers reported at least one attempt to
	quit smoking in the previous year and a greater proportion, 59.5%, expressed the desire
	Beck and Gautier, 2012, Guignard et al., 2015, Guignard et al., 2013). The Health to quit smoking (Guignard et al., 2015). In 2010, 31.8% of the current smokers discussed
	Barometer series was last conducted in 2014 (Guignard et al., 2015) but only the main their tobacco use with their health practitioner (Beck and Gautier, 2012).
	results have been published already, such as prevalence of smoking. The previous data Regarding exposure to second-hand smoke, approximately one third (35.8%) of the 15-75
	on smoking, behaviours and tobacco risk perception were collected in 2010 (Guignard et year-old current smokers in France reported that smoking occurred regularly inside their
	al., 2013). This series covers all forms of tobacco smoking, e.g. cigarettes, cigars and homes in 2014. Almost all respondents acknowledged that smoking can cause cancer:
	waterpipes, but does not include smokeless tobacco. The data on smokeless tobacco use 74.6% replied it "certainly" does and 23.3% "probably" (Beck and Gautier, 2012). The
	in France are retrieved from the Eurobarometer series, a European Commission edition, widest difference of opinion between smokers and non-smokers was their support of a
	whose last survey was conducted at the end of 2014 (European Commission, 2015a). tax increase in cigarettes: 61.9% of non-smokers were in favour of a tax increase on
	tobacco products while only 21.5% of smokers supported it (Beck and Gautier, 2012).
	unemployment was positively associated with waterpipe smoking (OR=1.4, p<0.05)
	(Guignard et al., 2013).
	The use of smokeless tobacco was rare in France in 2012, with virtually nobody reporting
	either regular or occasional use; 4% of the French respondents to the Eurobarometer
	survey reported having tried smokeless tobacco once or twice only (European
	A contribution to this meagre change in prevalence is the decrease in the level of daily Commission, 2015a).
	smoking in women from 26% in 2010 to 24% in 2014 (Guignard et al., 2015). This Few studies investigated the prevalence of smokers in immigrants in France (Wanner et
	downward trend in women's smoking habits was mainly observed in daily smokers aged al., 1995b, Berchet and Jusot, 2010). In the 1990s, Wanner et al. observed a higher
	20-44 years while daily smoking increased in 55-64 year-olds. The prevalence of smoking tobacco intake among Maghrebian immigrants than in French natives. In 2006, Berchet
	in men overall was stable between 2010 and 2014; hence the sex gap in smoking is and Jusot investigated the self-reported health status of 1 st and 2 nd generation
	reducing. The overall decreasing trend in smoking prevalence in the last decades had immigrants, compared to that of the natives. The proportion of current smokers in their
	recently stabilized and even inversed in some subgroups such as 45-64 years-old women sample was 24.1% in 1 st generation immigrants, 28.1% in 2 nd generation immigrants, and
	25.7% in natives. The study sample was representative of ordinary households living in

The Health Barometer 2010 has shown an increase of daily smokers prevalence since 2005, from 27.0% to 29.1% (p<0,001), and especially among women, from 22.9% to 26.0% (p<0,001)

[START_REF] Guignard | Le tabagisme en France: analyse de l'enquête Baromètre santé[END_REF]

. The 2014 edition indicated a decrease in smoking intensity, but a stable prevalence of current smokers with 34% of the French population being smokers

[START_REF] Guignard | La consommation de tabac en France en 2014: caractéristiques et évolutions récentes[END_REF]

. These figures remain well above those of other high-income countries with stringent tobacco control initiatives such as the United Kingdom, Canada and Australia (World Health Organisation, 2015). As described in the Health Barometer in France, smoking is higher among men than women, with 32.3% and 24.3% prevalence of daily smokers in 2014 respectively. Daily smoking decreased slightly from 29.1% in 2010 to 28.2% in 2014 (p=0.01)

[START_REF] Guignard | La consommation de tabac en France en 2014: caractéristiques et évolutions récentes[END_REF]

. and the unemployed; both groups have registered an increase in smoking prevalence

[START_REF] Beck | Increasing trends in smoking in France: mains results of the French Health Barometer, France[END_REF]

. The social inequalities in smoking, which widened between 2000 and 2010, were Waterpipe ever smokers represented 2.9% of the French population in 2010, or 9.0% of the total number of current smokers. The prevalence of waterpipe smoking is higher in men than in women, 3.9% and 2.0% respectively. The largest waterpipe smoking prevalence was observed in 15-19 year-olds (13.4%). After adjusting by sex and age, metropolitan France; however, the reduced sample size of immigrants did not allow conclusion to be drawn for the national immigrant population. To our knowledge, no other data were

  Oh et al., 2010), I developed a comprehensive questionnaire addressing not only tobacco use in all its forms but also other determinants of use. It was mainly based on the Global Adult Tobacco Survey questionnaire (World Health Organization, 2008). The questionnaire consists of 12 sections as shown in the Table 1 of in the manuscript for publication found in page 80, and approximately 820 variables spread over 77 pages. It was designed to be administered by a trained interviewer.

	The development of the finalised questionnaire was a particularly time-consuming
	activity in this thesis work (approximately 10 months), as it involved the gathering and
	harmonisation of all sections and items, creation of new questions when necessary and
	establishing a complex skip pattern according to smoking status (current, former, never),
	frequency of smoking (daily versus non-daily) and type of product. The interviewer was
	redirected to specific questions depending on the participant's type of tobacco use
	Studies (INED) recommended not to use a household survey sampling as participation
	would be too low. Another alternative approach can be using a telephone based survey,
	but this methodology has not yet been tried and validated to study the health of French
	immigrants.
	3.3 Questionnaire development

opposed to a convenience sample, a random sample to investigate tobacco use in immigrants in France -where no population register exist to facilitate the identification and recruitment of immigrants -could consist in a household survey: a survey that is administered at the household level. As in other household surveys' protocols, interviewers would have to go and ring at the doors, then identify and offer participation to the eligible respondents. In theory almost any population-based subject can be investigated through household surveys. However, in the case of tobacco use in immigrants in the French context, experts from the French Institute for Demographic Based on validated questionnaires from earlier French or international studies (Beck and Gautier, 2012, Gallus et al., 2014, World Health Organization, 2008, Simon and Clément, 2006, (smoking tobacco in all forms but shisha (manufactured cigarettes, hand-rolled cigarettes, pipes, cigars, cigarillos and other types), shisha smoking and/or smokeless tobacco) and also on the participant migration status (cf. history of tobacco use in the country of birth). The different combination of products and status of use results in many different profiles as displayed in Table 2.1 for smoked tobacco only. Similarly, different profiles are identified for smokeless tobacco use.

Table 2 .1: Tobacco smoking profiles according to current and past smoking exposure.

 2

Table 2 .

 2 2 shows the distribution of interviews conducted for each type of venue, with

	administration and recruitment times, for these 2 main interviewers. The venues most
	frequented by the general population -markets, universities and large shopping centers
	-provided most of the interviewees (76%) of the survey conducted by the 2 main
	interviewers. In these 2 interviewers, the average time of administration of the
	questionnaires was 12% shorter (29 minutes vs. 33 minutes) than for all interviewers
	combined (cf. results provided in the submitted manuscript). This can be explained by a
	progressive mastering of the questionnaire's complex skip pattern by those interviewers
	completing a larger number of interviews. Their average time of recruitment, i.e., the
	time required to enlist a new eligible participant, was similar to that of the 4 interviewers
	combined (29 minutes vs. 27 minutes). However, these 2 interviewers spent a significant

S. Ducarroz, AM. Schott, J. Schüz, ME. Leon

generation immigrant 2nd generation immigrant Total Total (n=49) Women (n=20) Men (n=29) Total (n=75) Women (n=37) Men (n=37) Total* (n=26) Women (n=17) Men (n=8)

Table 3 .1: Distribution of country or region of birth in 1 st generation immigrants with or without date of immigration in Denmark in 1978 to 2010 Region of birth 1 st generation immigrants w/o date of immigration 1 st generation immigrants

 3

	w/ date of immigration

Table 4 .2: Distribution of tobacco-related cancers in 1 st generation immigrants with or without date of immigration in Denmark in 1978 to 2010

 4

	Cancer type	1 st generation immigrants w/o date of immigration	1 st generation immigrants w/ date of immigration
		n	%	n	%
	Larynx	101	4,3%	78	5,6%
	Lung	1 018	43,8%	635	45,4%
	Adenocarcinoma	255	11,0%	185	13,2%
	Squamous cell	287	12,4%	168	12,0%
	Large cell carcinoma	73	3,1%	27	1,9%
	Small cell carcinoma	152	6,5%	95	6,8%
	Other	251	10,8%	160	11,4%
	Lower urinary tract	320	13,8%	97	6,9%
	Oropharynx	68	2,9%	60	4,3%
	Esophagus	94	4,0%	51	3,6%
	Oral cavity	138	5,9%	87	6,2%
	Liver	122	5,3%	99	7,1%
	Stomach	256	11,0%	187	13,4%
	Pancreas	206	8,9%	104	7,4%
	All TRC	2 323	100,0%	1398	100,0%

Table 5 .3: Tobacco-related cancers overall and lung cancers SIR by immigration status and region of birth in Danish men in 1978 to 2010

 5

		No. SIR (95% CI)	68 462 Referent	2 068 0.91 (0.87-0.95)*	108 0.93 (0.77-1.12)		68 570 Referent	0.99 (0.95-1.04)	395 1.04 (0.94-1.14)	160 0.97 (0.83-1.13)	169 1.09 (0.93-1.26)	18 0.74 (0.44-1.12)	48 1.30 (0.96-1.70)	127 0.84 (0.70-0.99)*
	Lung	No. SIR (95% CI)	61 298 Referent	1 653 0.86 (0.82-0.90)*	51 0.73 (0.54-0.94)*		61 349 Referent	0.96 (0.91-1.02)	295 0.89 (0.79-1.00)	109 0.77 (0.64-0.93)*	133 0.97 (0.81-1.14)	23 1.15 (0.73-1.67)	30 0.93 (0.62-1.29)	132 1.07 (0.89-1.26)
		No. SIR (95% CI)	129 760 Referent	3 721 0.89 (0.86-0.91)*	159 0.85 (0.73-0.99)*		129 919 Referent	0.98 (0.94-1.02)	690 0.97 (0.90-1.04)	269 0.88 (0.78-0.99)*	302 1.03 (0.92-1.15)	41 0.92 (0.66-1.23)	78 1.13 (0.89-1.39)	259 0.94 (0.83-1.06)	368 1.21 (1.09-1.34)*
	Person-yrs		77 420 046	4 340 497	2 513 834		79 933 880		555 902	248 175	189 028	77 276	41 423	409 146	340 876
	Population		3 098 622	330 289	129 056		3 227 678		47 992	16 485	16 455	10 671	4 381	19 406	19 244
		Immigration status	Native	1st generation immigrant	2nd generation immigrant	Region of birth	Denmark	Europe (excl. Denmark)	Nordic countries	Sweden	Norway	Iceland	Finland	Turkey	Former Yugoslavia 2

Table 6 .4: Other tobacco-related cancers SIR by immigration status and region of birth in Danish men in 1978 to 2010

 6

		SIR (95% CI)
		No.	10 296
		No. SIR (95% CI)	11 832 Referent
		No. SIR (95% CI)	4 624 Referent
		No. SIR (95% CI)	7 815 Referent
		No. SIR (95% CI)	6 099 Referent
		No. SIR (95% CI)	3 933 Referent
		No. SIR (95% CI)	17 979 Referent
	Larynx	No. SIR (95% CI)	5 884 Referent
		Immigration status	Native

  Trajectories and Origins study (TeO), in France[START_REF] Beauchemin | Trajectories and Origins[END_REF], has shown to be very effective in building a representative sample of 1 st and 2 nd generation immigrants: identification of the target population was done with the help of census information -in collaboration This would allow re-contacting the responder for additional information or quality check of former responses. In addition, the form of a telephone-based study has another advantage in terms of study efficiency as a larger target population is reachable at limited costs, and use of interpreters, when necessary, can more easily be organized.

	Nevertheless, nowadays more and more individuals rely less on telephone landlines and
	more on mobile services for which sampling frames typically used in random digit dialing
	are being used routinely in general population surveys, but would need to be assessed
	for completeness in the immigrant population and number of attempts or effort required
	to identify an eligible responder from a minority group (first generation immigrants)
	representing about 9% of the population.

with the census bureau (INSEE) -and administration of the questionnaire completed during several interviews. The quality of such a study has to be considered in balance with the time and complexity required for reaching collaboration with the census bureau, approval by the CNIL in the lengthy revision/approval process, its preparation and implementation. But the TeO study was conducted in response to a public mandate, and therefore not necessarily reproducible in ordinary research conditions for non-politically driven agendas conducted by researchers not mandated by the government.

Another alternative is the household survey, often conducted via telephone (e.g. Health Barometer).

  was decided for TOBAMIG to concentrate on non-European immigrants only and consequently not to include the European immigrants in the investigation of tobacco use, as their tobacco use and health behaviours might not differ as much from the French natives than that of the non-European immigrants. As explained in Chapter 2, non-European immigrants are expected to diverge more from the natives than the European In the case of Swedish immigrant users of Swedish snus moving into France, it would be relevant to register changes in tobacco use as snus is banned for sale in France. Further, as some European immigrant groups have resided in France for a longer time, including them would also

	allow further investigation into the phenomenon of acculturation relating to tobacco use
	in France. Nevertheless, including all immigrants may help preventing any selection of
	participants based on appearance, as interviewers would offer participation to everybody
	regardless of ethnic prototypes.

immigrants. This is based on the type of tobacco use prevailing in the different countries of origin, while the majority of Europeans smokers principally consume cigarettes at similar levels as French counterparts, North-Africans or South-East Asians populations, in the countries of origin, not only smoke at different level -which is especially true in women -but also use other products, e.g. shisha and smokeless tobacco (World Health Organisation, 2015). However, limitations are still inherent in their study. As differences in tobacco use still exists between European countries, such as elevated snus use in Nordic countries, it would also be of scientific interest to investigate how European immigrants' tobacco behaviours change with migration in France.

708 30,246,708 32,219,000 25,414 12,064 13,350 76,782 35,703 41,079

  This observation indicates two research paths: on one hand, developing the cancer registries in the European countries will allow investigating the immigrants' cancer in other European countries; on the other hand, in established highquality registers, improving the immigrant status variables to cover the regions or birth,

	Hommes Femmes Total Hommes Femmes	28,300 30,343 247,858 118,104 129,754	7,022 6,908 51,192 25,556 25,636	1,207 1,426 11,063 5,259 5,804	983 1,197 8,840 4,143 4,697
	Total	58,643	13,930	2,633	2,180
	Hommes Femmes	19,703 20,636	5,766 5,811	1,104 1,201	754 838
	Total	40,339	11,577	2,305	1,592
	Hommes Femmes	8,160 8,530	2,425 2,184	471 464	387 406
	Total	16,690	4,609	934	792
	Hommes Femmes	14,174 15,816	2,556 2,596	606 566	472 437
	Total Hommes Femmes Total Hommes Femmes Total Hommes Femmes Total	62,465,29,990	5,325,419 2,619,899 2,705,520 3,961 1,902 2,059 11,964 5,885 6,079 5,152	2,045,642 953,383 1,092,259 1,562 751 811 2,457 1,120 1,337 1,172	1,813,978 851,532 962,445 1,380 656 724 1,986 891 1,095 909
	EFFECTIFS	Population totale	Immigrés	Europe	Europe des 27	E s p a g n e

34 17 17 354 135 219 96 33 64 25 15 10 29 14 15 82 32 50 620 246 374

  Champ : Communes du Grand-Lyon ou limitrophe de plus de 9999 habitants, dont la proportion d'immigrés est supérieure a la moyenne nationale(8,5%) Source : Insee, recensement 2009, exploitation principale.

	TOTAL	4,143 4,697	1,116 1,107	15,957 15,088	7,788 7,751	1,811 1,814	3,640 2,635	2,717 2,888	4,094 4,370	1,322 1,250	2,772 3,121		Hommes Femmes
		8,840	2,223	31,045	15,539	3,626	6,275	5,605	8,464	2,572	5,892		Total
	Vénissieux	983 1,197	223 229	4,877 4,465	2,598 2,399	458 490	1,202 909	619 666	906 967	353 337	553 630		Hommes Femmes
		2,180	453	9,342	4,997	949	2,111	1,286	1,873	689	1,184		Total
	Vaulx-en-Velin	1,592 754 838	713 350 363	7,139 3,606 3,532	3,566 1,769 1,797	1,058 556 502	1,177 625 552	1,338 657 681	2,104 1,041 1,063	726 373 354	1,378 669 709		Total Hommes Femmes
	Saint-Fons	387 406	84 58	1,612 1,355	693 744	144 142	560 285	215 184	328 355	225 243	102 111		Hommes Femmes
		792	142	2,967	1,437	286	845	399	682	469	214		Total
	Rillieux-la-Pape	909 472 437	263 134 129	2,584 1,256 1,328	1,266 595 671	270 125 145	630 358 272	418 179 239	1,300 661 639	138 77 61	1,162 584 578		Total Hommes Femmes
	Lyon 8ème	891 1,095	229 242	3,916 3,768	1,675 1,728	471 480	789 512	981 1,049	714 756	165 111	550 645		Hommes Femmes
		1,986	470	7,684	3,403	950	1,301	2,029	1,470	275	1,194		Total
	Décines-Charpieu	1,380 656 724	182 96 87	1,330 690 639	871 460 411	113 57 55	211 107 104	135 67 68	1,035 443 592	274 130 145	761 313 447		Total Hommes Femmes
	Métropole	667,065 289,649 377,416	231,664 101,851 129,814	2,302,910 1,201,938 1,100,972	379,969 341,305 721,274	347,165 316,337 663,502	138,379 97,863 236,242	336,425 345,467 681,892		129,418 112,810 242,229		335,159 399,478 734,637	Hommes Femmes Total	62,465,
			Autres pays d'Europe	(hors UE27)	Afrique	Algéri e	Maroc	Tunisie	Autres pays d'Afrique	Asie	Turquie	Autres pays d'Asie	Autres pays	PROPORTIONS	Population totale

708 30,246,708 32,219,000 25,414 12,064 13,350 76,782 35,703 41,079

	30,343 247,858 118,104 129,754	22.77% 20.65% 21.64% 19.76%	4.70% 4.46% 4.45% 4.47%	3.94% 3.57% 3.51% 3.62%
	28,300	24.81%	4.26%	3.47%
	58,643	23.75%	4.49%	3.72%
	20,636	28.16%	5.82%	4.06%
	19,703	29.26%	5.60%	3.83%
	40,339	28.70%	5.71%	3.95%
	8,530	25.60%	5.44%	4.75%
	8,160	29.72%	5.77%	4.74%
	16,690	27.61%	5.60%	4.75%
	15,816	16.41%	3.58%	2.76%
	14,174	18.03%	4.28%	3.33%
	29,990	17.18%	3.91%	3.03%
		14.80%	3.25%	2.67%
		16.48%	3.14%	2.50%
		15.58%	3.20%	2.59%
		15.42%	6.07%	5.42%
		15.77%	6.23%	5.43%
		15.59%	6.15%	5.43%
		8.40%	3.39%	2.99%
		8.66%	3.15%	2.82%	0.37%
		8.53%	3.27%	2.90%	0.40%
		Immigrés	Europe	Europe des 27	Espagne

  Communes du Grand-Lyon ou limitrophe de plus de 9999 habitants, dont la proportion d'immigrés est supérieure a la moyenne nationale (8,5%) Source : Insee, recensement 2009, exploitation principale.

		3.62%	0.85%	11.63%	5.97%	1.40%	2.03%	2.23%	3.37%	0.96%	2.40%	0.29%
	TOTAL	3.51%	0.94%	13.51%	6.59%	1.53%	3.08%	2.30%	3.47%	1.12%	2.35%	0.21%
		3.57%	0.90%	12.53%	6.27%	1.46%	2.53%	2.26%	3.41%	1.04%	2.38%	0.25%
		3.94%	0.76%	14.72%	7.91%	1.62%	3.00%	2.20%	3.19%	1.11%	2.08%	0.16%
	Vénissieux	3.47%	0.79%	17.23%	9.18%	1.62%	4.25%	2.19%	3.20%	1.25%	1.96%	0.11%
		3.72%	0.77%	15.93%	8.52%	1.62%	3.60%	2.19%	3.19%	1.18%	2.02%	0.14%
		4.06%	1.76%	17.12%	8.71%	2.43%	2.68%	3.30%	5.15%	1.72%	3.43%	0.07%
	Vaulx-en-Velin	3.95% 3.83%	1.77% 1.78%	17.70% 18.30%	8.84% 8.98%	2.62% 2.82%	2.92% 3.17%	3.32% 3.33%	5.22% 5.29%	1.80% 1.89%	3.42% 3.40%	0.07% 0.07%
		4.75%	0.68%	15.89%	8.73%	1.66%	3.34%	2.16%	4.16%	2.85%	1.31%	0.12%
	Saint-Fons	4.74%	1.03%	19.75%	8.49%	1.77%	6.86%	2.64%	4.02%	2.76%	1.25%	0.18%
		4.75%	0.85%	17.78%	8.61%	1.71%	5.06%	2.39%	4.09%	2.81%	1.28%	0.15%
		2.76%	0.81%	8.40%	4.25%	0.92%	1.72%	1.51%	4.04%	0.39%	3.65%	0.40%
	Rillieux-la-Pape	3.03% 3.33%	0.88% 0.95%	8.62% 8.86%	4.22% 4.19%	0.90% 0.88%	2.10% 2.53%	1.39% 1.26%	4.33% 4.66%	0.46% 0.54%	3.88% 4.12%	0.32% 0.23%
		2.67%	0.59%	9.17%	4.21%	1.17%	1.25%	2.55%	1.84%	0.27%	1.57%	0.53%
	Lyon 8ème	2.50%	0.64%	10.97%	4.69%	1.32%	2.21%	2.75%	2.00%	0.46%	1.54%	0.38%
		2.59%	0.61%	10.01%	4.43%	1.24%	1.69%	2.64%	1.91%	0.36%	1.56%	0.46%
		5.42%	0.65%	4.79%	3.08%	0.42%	0.78%	0.51%	4.43%	1.08%	3.35%	0.13%
	Décines-Charpieu	5.43% 5.43%	0.72% 0.79%	5.23% 5.72%	3.43% 3.81%	0.44% 0.48%	0.83% 0.88%	0.53% 0.55%	4.07% 3.67%	1.08% 1.07%	2.99% 2.60%	0.14% 0.14%
		1.17%	0.40%	3.42%	1.06%	0.98%	0.30%	1.07%		0.35%		1.24%
	1.07% 0.96% Champ : Métropole Autres pays d'Europe (hors UE27) 0.37% 0.34% Afrique 3.69% 3.97% Al gérie 1.15% 1.26% Maroc 1.06% 1.15% Tunisie 0.38% 0.46% Autres pays d'Afri que 1.09% 1.11% Asie Turqui e 0.39% 0.43% Autres pays d'Asie Autres pays 1.18% 1.11%

coordination alternative places for sampling such as the Adoma residences and similar venues could be included in a larger study. The likelihood of stigmatizing potential participants could be minimized if sampling of French natives is also incorporated into the recruitment process. Incorporating sampling of French natives would comprise additional benefits including the possibility of obtaining tobacco use estimates in national counterparts for direct comparison to immigrants in the study and to nationals in the country of origin in other studies [START_REF] Koochek | Is migration to Sweden associated with increased prevalence of risk factors for cardiovascular disease?[END_REF].

In 2004-2005, the overall smoking prevalence estimates in 11 European countries in the population aged 50 years and older were similar between immigrants and the nativeborn population (Sole-Auro and Crimmins, 2008). However, this review also indicated evidence of major differences in smoking in immigrants by country of origin and sex in Europe. In few studies the level of smoking was found to be higher in immigrants than in in North African countries). To a lesser extent, the host-country has also a role in the difference in smoking behavior between immigrants and natives, depending on the level of the general population's smoking prevalence. However, the relationship is increasingly complex as evidenced by diverging trends which were observed. For instance, in most studies, Turkish immigrants exhibited a higher smoking than the natives of their hostcountry, while South Asian immigrants -and especially women -had a lower smoking prevalence than the natives.

Ethical approval

The IARC Ethical committee (IEC) was concerned with the potential of the original larger scale study to provoke stigma or discrimination, and therefore suggested carrying out first a pilot study. Although not done at the time, it would have been possible to discuss and appeal to the decision of the ethics committee by presenting tobacco use from another angle. A major confusion in their arguments was to consider tobacco use as a behavioural problem singled out in a minority group rather than as a morbid condition of dependence that entails substantially higher risk of several major chronic diseases. An addiction involves a treatment like any other serious illness, while behaviour implies a personal choice. Ethics committees must understand that the tobacco industry works to persuade people that the use of tobacco products is only a matter of adults informed choice. Since most adults begin using tobacco and become addicted in adolescence, the idea of choice is often wrong.

Length of the questionnaire

If any future study were to maintain participant anonymity, the length of the questionnaire should be reduced to allow increased completion of the questionnaire, as follow-up on missing responses cannot be done and responders' time availability when intercepted in public places would be limited. Along the same line, it is important to evaluate the length of the questionnaire in this setting of private interviews conducted in public places, as a balance between more detailed information on the one hand and higher completeness on the other. In our case we clearly observed that the completion rates of the questionnaire got reduced after each additional section. In this regard, I

Option 1 -Field anonymous face-to-face survey

On one side, in the TOBAMIG setting, the unplanned visits of the interviewers in public places to recruit the target populations did not allow consistent administration of the 30-45 minutes questionnaires in its entirety. Consequently, the completion rates decreased along the questionnaire sections, raising also the question of data quality.

A possible study derived from the TOBAMIG methodology would therefore be to use the same sampling methods. This would mean focusing on geographical areas with a high proportion of the immigrants' populations, within which venues that have high pedestrian frequentation would be listed and a given number randomly selected for conducting the interviews. Then, trained interviewers would be placed in these locations to identify eligible responders. When a participant is assessed as eligible, a modified questionnaire able to be administered in 10-15 minutes could be used. In a similar requires further investigation before comprehensive information is available, including tobacco use and associated tobacco-related morbidity and mortality.

Understanding the determinants of immigrant health outcomes is of major importance for several reasons. First, the right to the highest attainable health is a fundamental right stated in 1946, in the preamble of the constitution of the World Health Organization [START_REF] Grad | The Preamble of the Constitution of the World Health Organization[END_REF], and this come along with the principle of equity in health for the entire population. In addition, as immigrants are an increasingly important proportion of the EU population, more than 10% in 2014, they contribute significantly to the health status of the European populations. Finally, promoting and documenting the health of immigrants can also benefit to the natives, with lessons learned about the health protective factors associated with being an immigrant.

To further understand the association between health and the immigrant status, and to facilitate comparisons between countries, more research is required which should cover two aspects of data collection. On one hand, studies specially designed are needed that are culture-specific and when necessary using data collection instruments translated in the mother tongue of the target immigrant populations. On the other hand, in order to include immigrants in general surveys involving the whole population, as well as in registry-based studies, more validated instruments are needed, and larger sample size studies required.

As is common place in most epidemiologic surveys the sex and socio-economic conditions of respondents are included, this thesis has shown that all future studies focusing on immigrant populations should elicit information on the respondent's country of origin, length of stay in the host-country and, ideally, living conditions.

Our results support the findings previously established in the literature, e.g. lower incidence and mortality of TRC overall in the immigrants compared to the natives, large disparities in immigrants' TRC burden depending on country of birth and sex.

The two literature reviews outlined in Chapter 1 showed the lack of qualitative studies within the field of immigrant's health, and in particular of the tobacco burden in this population groups. This was also shown by Nielsen and Krasnik in a systematic review on self-perceived health in immigrants in Europe, in 2010, which identified only 17 length of stay and other determinants to be assessed, would contribute to a better understanding of the immigrants' health issues.

We know that smoking contributes to health inequalities within the national populations.

This thesis therefore provides elements to be considered to address the issue of immigrants' health and tobacco, both in a research perspective but also to elaborate public policies aiming at tackling health inequalities; and this last need to target the most affected groups of immigrants, according to their countries of origin.

The ultimate aim of the information collected through our investigation would be its usefulness in gauging if tobacco control measures in place in France are inclusive of the needs of minority groups that may differ from the general population.

Even if the current literature is scarce compared to the increasingly important size of the immigrant populations in Europe, many countries have actively integrated immigrant health into their health agendas. This is evidenced through the policies and public health interventions being implemented which are crucial addressing the immigrants' health behaviours as well as their access to healthcare. In particular, health professionals and stakeholders should be aware of the patterns of tobacco use in the immigrant populations as well as the tobacco-related cancer burden, as shown in this thesis, to adapt and improve existing prevention programs and develop new programs. Studies have observed that the smoking in immigrants evolved differently in men and women with acculturation: more acculturated women were more likely to smoke than less acculturated women; the contrary was observed in men (Reiss et al., 2014b). In this regard, prevention programs in immigrants should use different strategies in men and women, targeting respectively to reduce the smoking prevalence and to prevent initiation. In order to assess the effect of acculturation on the tobacco use patterns in immigrants, it is important to consider acculturation as a process starting in the country of origin. Therefore, studies addressing the smoking in immigrants need to consider the complexity of this process that only longitudinal studies can properly reveal the mechanisms and determinants in action.

Appendices