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Background: Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods: Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings: During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p Interpretation: If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

En plus de son role de facteur de risque du cancer du sein apres la menopause, l’obesite a ete associee a un moins bon pronostic du cancer du sein. Cependant, le niveau de preuve de cette association n’est pas encore satisfaisant, car les etudes sur le sujet presentent des differences methodologiques importantes. Cet article a donc pour objectif de realiser un etat de l’art des relations entre obesite et survie apres cancer du sein.

International audience; Objective Functional gastrointestinal disorders (FGID) such as diarrhoea and constipation can reflect intestinal dysfunction, especially with regard to intestinal microbiota, which, in turn, have been associated with chronic conditions, including obesity and insulin resistance. However, little is known of the association between FGID and type 2 diabetes (T2D) risk. Design and methods This analysis aimed to determine the influence of diarrhoea, constipation and alternating bouts of diarrhoea/constipation on T2D risk in 62,683 women from the prospective E3N–EPIC cohort. Results A total of 1795 T2D cases were recorded during follow-up. Compared with women who had normal gastrointestinal transits, women with chronic diarrhoea or alternating diarrhoea/constipation were at increased risk of T2D (HR: 1.29, 95% CI: 1.00–1.65 vs. HR: 1.32, 95% CI: 1.15–1.52, respectively), whereas women with constipation had a decreased risk (HR: 0.67, 95% CI: 0.57–0.78). There was no interaction between FGID and body mass index for risk of T2D. Also, these associations were independent of dietary habits such as coffee, fruit and vegetable consumption, and even of the use of laxatives and psychotropic drugs. Conclusion The present analysis showed, for the first time, a limited association between FGID and T2D risk in a large prospective cohort, and supports the hypothesis of a relationship between gastrointestinal function and diabetes. The presence of gastrointestinal transit disorders may assist in screening for subjects at higher risk of diabetes beyond the conventional risk factors

Objectifs Les complements alimentaires a base d’isoflavones de soja sont presentes comme une alternative naturelle au traitement hormonal de la menopause. Leur effet potentiel sur le risque de cancer du sein, jusqu’a present rarement evalue « en vie reelle », est controverse. Nous avons donc etudie l’association entre la consommation de ces complements alimentaires et le risque de cancer du sein de maniere prospective dans une cohorte de femmes âgees de plus de 50 ans. Methode Au total, 76 442 femmes de la cohorte E3 N, nees entre 1925 et 1950, ont ete suivies entre les annees 2000 et 2011 (11,2 annees en moyenne) durant lesquelles 3608 cas incidents de cancers du sein sont survenus. Des informations sur leur consommation de complements alimentaires a base de soja ont ete recueillies tous les deux a trois ans. Des modeles de Cox multivaries nous ont permis d’estimer les risques relatifs (RR) de cancer du sein associes a une consommation en cours ou passee de complements alimentaires a base de soja, ainsi que leurs intervalles de confiance (IC) a 95 %. Resultats La prise de complements au soja etait associee a des RR egaux a 0,92 (IC 95 % = 0,76–1,11) pour les cancers du sein tous types confondus, 0,78 (IC 95 % = 0,60–0,99) pour les cancers de statut positif des recepteurs aux estrogenes (RE + ) et 2,01 (IC 95 % = 1,41–2,86) pour les cancers de statut negatif (RE–), pour une utilisation en cours en comparaison avec le fait de n’en avoir jamais consomme. Nous n’avons pas observe d’association entre la consommation passee de complements au soja et le risque de cancer du sein. Nous avons mis en evidence un effet modificateur des antecedents familiaux de cancer du sein (pinteraction = 0,03) et du statut menopausique (pinteraction = 0,04) : les RR associes a une utilisation en cours etaient egaux a 1,36 (IC 95 % = 0,95–1,93) parmi les femmes ayant un antecedent familial de cancer du sein chez une parente de premier degre et a 0,82 (IC 95 % = 0,65–1,02) parmi les femmes sans antecedent familial ; les RR etaient egaux a 1,06 (IC 95 % = 0,87–1,30) parmi les femmes menopausees depuis plus de cinq ans et a 0,50 (IC 95 % = 0,31–0,81) parmi les femmes en perimenopause ou menopausees depuis moins de cinq ans. Conclusion Notre etude a mis en evidence des associations opposees entre la consommation de complements alimentaires a base d’isoflavones de soja et les risques de cancers du sein selon le statut des recepteurs aux estrogenes. Elle suggere egalement qu’ils devraient etre utilises avec prudence par les femmes ayant un antecedent familial de cancer du sein. Enfin, nos resultats devraient encourager la mise en œuvre de nouvelles etudes chez des femmes non menopausees ou menopausees depuis peu de temps afin de verifier si le profil de risque de ces complements pourrait etre plus favorable parmi celles-ci.

BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.

Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation. (C) 2011 Elsevier Ltd. All rights reserved.

Objectives:To describe and compare the consumption of dairy products in cohorts included in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods:Data from single 24-hour dietary recall interviews collected through a highly standardised computer-based program (EPIC-SOFT) in 27 redefined centres in 10 European countries between 1995 and 2000. From a total random sample of 36 900, 22 924 women and 13 031 men were selected after exclusion of subjects under 35 and over 74 years of age.Results:A high total consumption of dairy products was reported in most of the centres in Spain and in the UK cohort sampled from the general population, as well as in the Dutch, Swedish and Danish centres. A somewhat low consumption was reported in the Greek centre and in some of the Italian centres (Ragusa and Turin). In all centres and for both sexes, milk constituted the dairy sub-group with the largest proportion (in grams) of total dairy consumption, followed by yoghurt and other fermented milk products, and cheese. Still, there was a wide range in the contributions of the different dairy sub-groups between centres. The Spanish and Nordic centres generally reported a high consumption of milk, the Swedish and Dutch centres reported a high consumption of yoghurt and other fermented milk products, whereas the highest consumption of cheese was reported in the French centres.Conclusion:The results demonstrate both quantitative and qualitative disparities in dairy product consumption among the EPIC centres. This offers a sound starting point for analyses of associations between dairy intake and chronic diseases such as cancer.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

Objectif L’utilisation des bisphosphonates a fortement augmente depuis le debut des annees 2000, principalement dans le traitement de l’osteoporose postmenopausique. Les etudes precliniques suggerent qu’ils puissent egalement avoir une activite antitumorale. Nous avons donc evalue l’association entre l’utilisation de bisphosphonates et l’incidence de cancer du sein dans la cohorte francaise E3N. Methode Au total, 64 438 femmes de la cohorte E3N ont ete incluses dans les analyses. Au cours d’un suivi moyen de 7,2 annees (2004–2011), 2407 cancers du sein primitifs ont ete diagnostiques. Les donnees issues des questionnaires biennaux de suivi ont ete appariees avec des donnees precisant le code CIP et la date de delivrance des medicaments rembourses aux participantes de la cohorte depuis l’annee 2004. L’exposition aux bisphosphonates a ete caracterisee a partir de ces donnees de remboursement. Les donnees sur les facteurs de confusion potentiels (facteurs de risque cliniques de fracture osteoporotique, surveillance de la densite minerale osseuse, facteurs de risque de cancer du sein) provenaient principalement des questionnaires de suivi. Les hazard ratios (HR) de cancer du sein et leur intervalle de confiance (IC) a 95 % ont ete estimes a l’aide de modeles de Cox multivaries, dans lesquels l’exposition aux bisphosphonates etait dependante du temps. Resultats Nous n’avons pas trouve de diminution du risque de cancer du sein avec l’utilisation de bisphosphonates ( HR 1,0 ; IC 95 % 0,9–1,1, compare au fait de n’avoir jamais ete expose). Nous n’avons pas mis en evidence d’interaction significative avec l’âge, l’indice de masse corporelle, le delai depuis la menopause, la prise de traitements hormonaux de la menopause, de calcium ou de vitamine D. Les analyses n’ont pas montre de variations de risque en fonction de la molecule utilisee (acide alendronique/acide risedronique/acide ibandronique/autres), et nous n’avons pas trouve de tendance significative en fonction de la dose cumulee, de la duree d’utilisation ou du delai depuis la derniere utilisation. En revanche, nous avons observe une diminution significative du risque de cancer du sein uniquement dans la premiere annee suivant l’initiation du traitement par bisphosphonates ( HR 0,6 ; IC 95 % 0,4–0,9). Des donnees complementaires suggerent que ce resultat puisse s’expliquer par un biais de surveillance, le traitement par bisphosphonates etant preferentiellement prescrit aux femmes ayant realise recemment une mammographie (et donc, avec une probabilite plus faible de diagnostic d’un cancer du sein dans les mois suivants). Enfin, nous n’avons pas trouve de variation significative de l’association bisphosphonates-cancer du sein en fonction du type de cancer du sein considere : ER+ ( HR 1,0 ; IC 95 % 0,8–1,1), ER- ( HR 1,0 ; IC 95 % 0,7–1,5), invasif (HR 1,0 ; IC 95 % 0,8–1,1) ou in situ ( HR 0,9 ; IC 95 % 0,6–1,3). Conclusion Nos resultats ne sont pas en faveur d’un effet protecteur vis-a-vis du risque de cancer du sein des bisphosphonates utilises dans le traitement de l’osteoporose post-menopausique.

OBJECTIVE To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries. RESEARCH DESIGN AND METHODS We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0–18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders. RESULTS The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7–10 points) and high adherence to MDP (rMED 11–18 points) were 0.93 (95% CI 0.86–1.01) and 0.88 (0.79–0.97), respectively, compared with individuals with low adherence to MDP (0–6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people CONCLUSIONS In this large prospective study, adherence to the MDP, as defined by rMED, was associated with a small reduction in the risk of developing type 2 diabetes in this European population.

Udgivelsesdato: 2010-Jul-27 Objective:The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Subjects:This study included a representative sample of 24 310 randomly selected EPIC participants.Methods:Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders.Results:In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (beta=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (beta=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake.Conclusion:Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.International Journal of Obesity advance online publication, 27 July 2010; doi:10.1038/ijo.2010.142.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 39 - N° 4 - p. 310-317

12 GermanInstituteof HumanNutritionPotsdam-Rehbruecke,Nuthetal,Potsdam,Germany, 13 JuliusCenterforHealthSciencesandPrimaryCare,UniversityMedical CenterUtrecht,Utrecht,theNetherlands, 14 DivisionofEpidemiology,PublicHealthandPrimaryCare,ImperialCollege,London,UK, 15 Centerfor NutritionandHealth,NationalInstituteofPublicHealthandtheEnvironment(RIVM),Bilthoven,theNetherlands, 16 PublicHealthDepartmentof

Mediterranean diet is associated with lower incidence of coronary heart disease, and two randomised trials indicated that it improves prognosis of coronary patients. These trials, however, relied on a total of 100 deaths and evaluated designer diets in the clinical context. We have evaluated the association of adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, with survival among elderly with previous myocardial infarction within the European Prospective Investigation into Cancer and nutrition (EPIC) study. As of December 2003, after a median follow-up of 6.7 years, 2671 EPIC participants from nine countries were 60 years or older and had prevalent myocardial infarction but no stroke or cancer at enrolment, complete information on dietary intakes and important covariates and known survival status. Adherence to the modified Mediterranean diet was assessed through a 10-unit-scale. Mortality ratio in relation to modified Mediterranean diet was estimated through Cox regression controlling for possible confounding. Increased adherence to modified Mediterranean diet by two units was associated with 18% lower overall mortality rate (95% confidence interval 7-27%, fixed effects model). There was no significant heterogeneity by sex, age at enrolment, or country, although the association tended to be less evident among northern Europeans. Associations between food groups contributing to the modified Mediterranean diet and mortality were generally weak. A diet inspired by the Mediterranean pattern that can be easily adopted by Western populations is associated with substantial reduction of total mortality of coronary patients in the community. © 2007 Springer Science+Business Media B.V.

Background:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.Methods:In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.Results:Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.Conclusions:Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.British Journal of Cancer advance online publication, 5 March 2015; doi:10.1038/bjc.2014.654 www.bjcancer.com.

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes?SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause.WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health.STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000.PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale.MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes.WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest.

In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age.

Objective To examine the validity of self-reported values for current anthropometric measurements and factors related to misreporting. Design E3N, a prospective cohort study of cancer risk factors, conducted in France and part of the European Prospective Investigation on Cancer. E3N comprises 100,000 women, born between 1925 and 1950, followed with self-administered questionnaires sent every 18 to 24 months starting in 1990. Subjects 152 women for the validation study of self-reported anthropometric measurements, and 91,815 women selected to evaluate factors affecting misreporting of body silhouette. Statistical analysis Paired t tests, Pearson and Spearman correlations were applied to evaluate the validity of self-reported measures, and analysis of variance and logistic regression were used to assess the factors influencing misreporting of silhouette. Results The correlation coefficients between self- and external measurements were high. All but sitting height ( r =0.56) were more than 0.80, with weight and bust (nipples) measurement correlation coefficients attaining 0.94. The correlation between body mass index (BMI), measured by the technician and the self-reported silhouette, was 0.78. Small height was always associated with misclassification. Specific factors related to a more favorable perception of body silhouette were: being overweight, small height, younger age, and a lower level of education. These women were also more frequently unmarried, more physically active, and had a slender body shape during adolescence. Results denoting a less favorable perception of body shape were reversed. Conclusion/Applications Self-reported measurements (made with or without help) are valid measures in epidemio-logical studies. Body silhouettes are simple and useful indicators of body mass index. However they should be interpreted with caution in certain instances, especially for overweight subjects. J Am Diet Assoc. 2002;102:1779-1784.

Introduction et but de l’etude La prise de complement en vitamine C est courante en France, mais son effet a long terme sur la sante est mal connu. Les etudes sur la prise de complement en vitamine C et le risque de cancer du sein sont contradictoires. Notre objectif etait d’etudier si le niveau d’apports alimentaires en vitamine C pouvait influencer la relation entre prise de complement en vitamine C et risque de cancer du sein dans la cohorte E3 N. Materiel et methodes Entre 1995 et 2008, 2482 cas de cancer du sein invasifs incidents ont ete diagnostiques parmi 57 403 femmes menopausees de la cohorte E3 N. La prise de complement en vitamine C a ete estimee dans des questionnaires envoyes en 1995, 2000, 2002, et 2005. Les apports alimentaires en vitamine C ont ete estimes a partir d’un questionnaire alimentaire de frequence semi-quantitatif envoye entre 1993 et 1995. Les risques relatifs de cancer du sein invasif (HR) et les intervalles de confiances a 95 % (IC 95 %) ont ete estimes a partir de modeles de Cox multivaries avec l’âge en echelle de temps. Resultats La prise de complement en vitamine C (au moins une fois par rapport a jamais) n’etait pas associee au risque de cancer du sein apres la menopause globalement. Elle etait associee a une augmentation du risque dans le quartile d’apports alimentaires en vitamine C le plus eleve (HR = 1,31, IC 95 % = [1,03–1,66]), mais pas dans les autres quartiles (pinteraction = 0,03). Le quartile d’apports alimentaires en vitamine C le plus eleve etait associe a une diminution de risque de cancer du sein apres la menopause chez les non-utilisatrices de complement en vitamine C (HR = 0,87, IC 95 % = [0,77–0,99], ptendance = 0,07), mais pas chez les utilisatrices de complement en vitamine C (HR = 1,17, IC 95 % = [0,85–1,62], ptendance = 0,29). Conclusion Nos resultats suggerent une potentielle relation en -U ou en -J entre les apports totaux en vitamine C et le risque de cancer du sein. En termes de sante publique, nos resultats suggerent que la prise de complement en vitamine C pourrait augmenter le risque de cancer du sein chez les femmes ayant deja des apports alimentaires en vitamine C eleves.

Introduction et but de l’etude Le World Cancer Research Fund (WCRF) a etabli des recommandations nutritionnelles destinees a la prevention primaire et tertiaire des cancers mais peu de donnees de la litterature permettent de savoir si elles sont suivies. Le but de cette etude a ete d’evaluer l’impact d’un diagnostic de cancer sur l’evolution a long terme de l’alimentation chez des femmes de l’etude E3 N, et d’evaluer comment l’environnement socioeconomique intervenait dans cette relation. Materiel et methodes Un total de 55 223 femmes issues de la cohorte E3 N a ete inclus. Elles ont toutes repondu a un questionnaire de frequence alimentaire en 1993 et 2005, ce qui nous a permis d’estimer des apports alimentaires quotidiens moyens aux deux temps. Des donnees socioeconomiques a l’echelle individuelle (niveau d’education, nombre d’enfants, activite professionnelle, revenus) et contextuelle (zone d’habitation, indice de defaveur social de la zone de residence-FDep99) ont egalement ete utilisees. Entre 1993 et 2005, 3678 femmes ont ete diagnostiquees d’un cancer. Des modeles de regression lineaire ont ete utilises pour evaluer si le diagnostic de cancer avait un impact sur l’evolution des apports alimentaires. Les analyses ont ete stratifiees par groupe socioeconomique et les modeles ont ete ajustes sur l’âge, l’indice de masse corporelle, l’activite physique, les apports des differents groupes alimentaires en 1993 et le temps ecoule entre le premier questionnaire de frequence alimentaire et la survenue du cancer. Resultats Apres survenue d’un cancer, les femmes augmentaient plus leur consommation de fruits que celles n’ayant pas eu de cancer lorsqu’elles avaient un niveau d’education eleve (+ 0,24 portions ; p = 0,02) ; avaient eu trois enfants ou plus (+ 0,30 portions ; p = 0,01) ; n’avaient pas d’activite professionnelle (femmes n’ayant jamais travaille ou a la retraite) (+ 0,13 portions ; p = 0,002) ; ou avaient de hauts revenus (+ 0,28 portions ; p = 0,005). Pour ce qui est de l’environnement socioeconomique contextuel, apres survenue d’un cancer, les femmes augmentaient plus leur consommation de fruits que celles n’ayant pas eu de cancer lorsqu’elles vivaient dans le sud de la France (+ 0,30 portions ; p = 0,008) ; vivaient dans l’ouest (+ 0,42 portions ; p = 0,04) ou dans des zones peu defavorisees (+ 0,23 portions ; p = 0,04). Conclusion Nous avons observe que seules les femmes de statut socioeconomique eleve modifiaient favorablement leur alimentation suite a la survenue de cancer mais seule leur consommation en fruits etait augmentee, ce qui suggere la necessite de mieux diffuser les messages de prevention apres cancer, avec une attention particuliere pour les milieux moins favorises. Les recommandations nutritionnelles liees aux cancers auraient besoin d’etre modulees selon l’environnement socioeconomique des populations. Il est egalement primordial de poursuivre a communiquer sur l’importance d’adopter une alimentation saine en prevention primaire et tertiaire des cancers.

The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and

Objectif L’objectif de cette etude est d’evaluer l’association entre le groupe (A, B, AB, O), le rhesus (Positif, Negatif), la combinaison des deux (ABO × Rhesus) et le risque de diabete de type 2 (DT2). Materiels et methodes Entre 1990 et 2008, 82 104 participantes de la cohorte E3N ont ete suivies. Des modeles de Cox ont ete utilises pour calculer les rapports de risque (RR) et leurs intervalles de confiance a 95 % (IC 95 %). Resultats Par rapport aux participantes du groupe sanguin O, celles du groupe A (RR = 1,10, IC 95 % 1,02-1,18) et B (RR = 1,21, IC 95 % 1,07-1,36) avaient une augmentation du risque de DT2. Le groupe AB etait a la limite de la significativite statistique (RR = 1,17, 95 % IC 0,99-1,39). En revanche, aucune difference de risque significative n’a ete observe entre les rhesus positif et negatif (RR = 0,96, IC 95 % 0,88-1,05). En combinant les deux informations et en prenant les femmes du groupe O- en reference, nous avons observe un sur-risque pour les femmes de groupe A + (RR = 1,17, IC 95 % 1,00-1,35), A- (RR = 1,22, IC 95 % 1,03-1,45), ainsi que pour le groupe AB + (RR = 1,26, IC 95 % 1,02-1,57). L’association la plus prononcee a ete observee pour le groupe B + (RR = 1,35, IC 95 % 1,13-1,60). Les autres groupes n’etaient pas associes au risque de DT2. Conclusion Il s’agit de la premiere etude prospective suggerant que le groupe sanguin est associe au risque de DT2. Par rapport aux autres groupes, les personnes du groupe O presentaient un risque diminue de DT2. Le groupe san-guin est une information facile a recueillir que les futures etudes sur le DT2 devraient prendre en compte. Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification. What's new? Many factors can affect susceptibility to breast cancer, including menopausal status and diet. This study investigated the association between breast cancer and an adapted version of the "Mediterranean diet," excluding alcohol. They found that the diet reduced the risk of breast cancer by 6% overall, and by 7% in postmenopausal women. For tumors lacking the estrogen or progesterone receptors, however, the diet reduced risk by 20% in postmenopausal women. Copyright © 2012 UICC.

AIMS/HYPOTHESIS: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults.METHODS: We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence.RESULTS: In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence.CONCLUSIONS/INTERPRETATION: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

Objectifs Les benzodiazepines et apparentees (BZD) sont utilisees largement dans le traitement de l’insomnie et de l’anxiete, souvent en association entre elles ou avec des antidepresseurs. Les etudes sur leur lien avec la morbimortalite cardiovasculaire (16 etudes observationnelles) sont conflictuelles, cinq d’entre elles montrant une augmentation de risque. Nous avons donc decide d’etudier l’association entre prise de BZD et mortalite cardiovasculaire dans une large cohorte francaise. Methodes Les Hazard ratios (HR) de mortalite cardiovasculaire et leurs intervalles de confiance (IC) a 95 % ont ete estimes par des modeles de Cox chez 85 349 femmes affiliees a une mutuelle d’enseignants, nees entre 1925 et 1950, parmi lesquelles 506 deces cardiovasculaires sont survenus au cours du suivi (2004–2011). Nous avons utilise les donnees concernant tous les medicaments rembourses depuis 2004 a chaque participante de la cohorte (nom, dosage et date de delivrance), les causes de deces communiquees par le CepiDc, et de nombreuses variables d’ajustement issues d’auto-questionnaires de suivi biennal. Les variables d’ajustement et d’exposition ont ete introduites dans les modeles comme variables dependantes du temps, afin de prendre en compte leur mise a jour au cours du suivi. Resultats Dans le modele ajuste seulement sur l’âge, l’exposition aux BZD etait associee a une augmentation marquee de la mortalite cardiovasculaire, avec notamment un doublement de risque (HR de 1,98 ; IC 95 % 1,62–2,43) si l’exposition etait recente (dans les trois mois precedents). Neanmoins, la simple introduction dans le modele des remboursements d’antidepresseurs apres 2004 et de la consommation de psychotropes auto-rapportees avant 2004 faisait disparaitre les associations entre BZD et mortalite cardiovasculaire, avec des HRs tres proches de 1. Nous avons ensuite selectionne les autres variables confondantes par une procedure pas-a-pas : sont venus s’ajouter dans le modele final la consommation de medicaments indiques dans le traitement des maladies cardiovasculaires, et un indicateur d’utilisation de soins medicaux. Dans ce modele, les HRs de mortalite cardiovasculaire associes a la prise de BZD etaient de 1,02 (IC 95 % : 0,79–1,32), 0,95 (IC 95 % : 0,72–1,27) et 0,98 (IC 95 % : 0,71–1,36) si le traitement etait en cours ou arrete depuis moins de trois mois, arrete depuis trois mois a deux ans, ou depuis plus de deux ans, respectivement. Pour les antidepresseurs, les HRs correspondants etaient de 2,40 (IC 95 % : 1,88–3,05), 1,97 (IC 95 % : 1,44–2,69) et 1,05 (IC 95 % : 0,70–1,57). Conclusion Notre etude ne met pas en evidence d’effet aigu des benzodiazepines vis-a-vis du risque de deces d’origine cardiovasculaire. Elle montre l’importance, dans les etudes sur les BZD, de la prise en compte de la consommation d’antidepresseurs, qui peut jouer un role de confusion important. Elle suggere que la prise d’antidepresseurs soit associee a une augmentation du risque de deces d’origine cardiovasculaire. Cette relation, plausible du fait des mecanismes d’action cardiovasculaire des antidepresseurs, doit etre confirmee par une etude specifique.

Background: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.Methods:Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables.Results:Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (O=R1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction0.154). Conclusion: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk. © 2012 Cancer Research UK All rights reserved.

BACKGROUND: Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Data on food consumption and follow-up on cancer incidence was available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 non-cardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores (DDSs) were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. RESULTS: Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous HR per 2 products increment 0.88; 95%CI 0.79-0.97 and 0.76; 95%CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. CONCLUSION: Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors can not be excluded. © 2012 Wiley-Liss, Inc.

Background: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. Methods: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. Results: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, 52 vs ≤45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. Conclusion: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors. © 2011 Cancer Research UK All rights reserved.

OBJECTIVE We evaluated the relationship between hip and waist circumferences (HCs, WCs), waist-to-hip ratio, height, weight and body mass index (BMI) and breast cancer risk according to menopausal status of women and cancer hormone receptor status. DESIGN We used data from the French E3N longitudinal prospective cohort. SUBJECTS In the total population of 63 726 women who were analyzed, 1887 breast cancer cases were diagnosed during follow-up. RESULTS Among postmenopausal women, the risk of ER+/PR+ breast cancer increased with increasing weight, BMI, and both HCs and WCs, although these two associations disappeared after adjustment for BMI. No association was seen with ER-/PR- breast cancers. Among premenopausal women, among the different factors studied, HC only (no association was observed for any of the different factors studied except for HC) was associated with an increased risk of ER+/PR+ breast cancer after adjustment for BMI (hazard ratio (HR)=1.65; (1.04-2.62) when comparing the highest to lowest tertile; P-trend across tertiles=0.03) and of ER-/PR- breast cancer both before and after adjustment for BMI (HR=2.85 (1.33-6.13); P-trend

OBJECTIVE To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries. RESEARCH DESIGN AND METHODS We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0–18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders. RESULTS The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7–10 points) and high adherence to MDP (rMED 11–18 points) were 0.93 (95% CI 0.86–1.01) and 0.88 (0.79–0.97), respectively, compared with individuals with low adherence to MDP (0–6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people

Modern molecular genetic epidemiology is scaled towards large-scale analyses, including genome wide association studies (GWAS) containing hundreds of thousands to millions of single nucleotide polymorphisms. In addition to generating information on alleles at each SNP, GWAS can also be used to evaluate copy number variation (CNVs) across the genome. Traditionally, these studies have been carried out using DNA extracted from lymphocytes in blood samples. More recently, the use of DNA extracted from less invasive methods has become attractive in epidemiological studies. Here, we examine the feasibility of using DNA from saliva to assess CNVs in a pangenome study. We have compared SNP and CNV genotypes among 30 individuals genotyped with the Affymetrix GeneChip NspI genotyping array using DNA from blood and saliva samples of the same individual. In general, while we find that the DNA extracted from these cells is of sufficient quantity and quality to genotype SNPs in a GWAS setting, the results of CNV analyses differed between blood and saliva samples from the same individual, particularly for shorter CNV regions.

Introduction Un desequilibre acidobasique chronique pourrait favoriser l'insulino-resistance. Mais, a l'heure actuelle, aucune etude prospective n'a evalue le risque de diabete de type 2 associe a une charge acide elevee dans l'alimentation. Materiels et methodes A partir de 1993, 66 485 femmes de la cohorte E3NEPIC ont ete suivies pendant 14 ans. Les scores PRAL (potential renal acid load) et NEAP (net endogenous acid production), refletant la charge acide de l'alimentation ont ete calcules a partir de l'apport en certains nutriments. Un score PRAL positif reflete une charge acide de l'alimentation, un score negatif refletant une charge basique. Des modeles de Cox multiajustes ont ensuite permis d'estimer des risques relatifs (RR) associes aux quartiles des scores PRAL et NEAP. Resultats Pendant le suivi, 1,372 cas de diabete de type 2 incidents ont ete identifies. Dans la population generale, les femmes ayant le PRAL le plus eleve (PRAL ≥ 7mEq/jr) etaient a risque accru de diabete (RR=1,56 [1,29–1,90]), par rapport aux femmes ayant des valeurs faibles (PRAL 2 , RR=1,96 [1,43–2,69]) que pour les femmes en surpoids (IMC ≥ 25kg/m 2 , RR=1,28 [1,00–1,64]. Les resultats pour le score NEAP etait similaires. Conclusion Cette etude met en evidence, pour la premiere fois dans une etude de cohorte prospective, une association directe entre la charge acide dans l'alimentation et le risque de diabete de type 2, independamment des autres facteurs de risque de diabete connus. Si ces resultats venaient a etre confirmes dans d'autres etudes, la promotion d'un regime alimentaire ayant une faible charge acide pourrait etre envisagee dans le cadre de la prevention primaire du diabete.

The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.

Udgivelsesdato: 2010-Jul-15 The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of >/=3.0 mg/L versus

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.

The objective of this work is to estimate the trends of the incidence of breast cancer until 2018, in the French context on the basis of an age cohort model. The model extrapolates the trend of incidence rate per generation and age, incorporates the effects of demographic changes in the female population in terms of size and age structure and simulates the impact of the withdrawal of the use of hormone therapy for menopause (HTM) under different assumptions. The results suggest a continuous growth in the number of incident cases that would increase from 49,814 to 64,621 between 2005 and 2018. Changes in incidence following the HTM use withdrawal, should be moderate and transient. The most important epidemiological parameters in explaining the future incidence of breast cancer remains the "cohort" effect that continues to have a significant impact until the extinction of cohorts for which the increase was more marked (birth years 1920 to 1945). This factor alone explains 18% of the growth in the number of incident cases in 2018, while the effect of population growth account for 6.6%, the cessation of HTM a 6.4% decrease and aging a 4.6% growth.

Udgivelsesdato: 2010-Jan-28 Abstract. Bamia C, Halkjaer J, Lagiou P, Trichopoulos D, Tjønneland A, Berentzen TL, Overvad K, Clavel-Chapelon F, Boutron-Ruault M-C, Rohrmann S, Linseisen J, Steffen A, Boeing H, May AM, Peeters PH, Bas Bueno-de-Mesquita H, van den Berg SW, Dorronsoro M, Barricarte A, Rodriguez Suarez L, Navarro C, González CA, Boffetta P, Pala V, Hallmans G, Trichopoulou A (University of Athens, Athens, Greece; Institute of Cancer Epidemiology, Copenhagen, Denmark; Harvard School of Public Health, Boston, MA, USA; Bureau of Epidemiologic Research, Athens, Greece; Hellenic Health Foundation, Athens, Greece; Institute of Preventive Medicine, Copenhagen, Denmark; Institute of Public Health, Aarhus University, Aarhus, Denmark; Center for Cardiovascular Research, Aalborg, Denmark; Institut Gustave-Roussy, Paris, France; German Cancer Research Centre, Heidelberg, Germany; Institute of Epidemiology, Potsdam, Germany; German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany; University Medical Center Utrecht, Utrecht, the Netherlands; Public Health and Primary Care, London, UK; National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Public Health Department of Gipuzkoa & Ciberesp, San Sebastian, Spain; Health Institute of Navarra, Pamplona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Health and Healthcare services council, Asturias, Spain; Murcia Regional Health Council, Murcia, Spain; Catalan Institute of Oncology, Barcelona, Spain; International Agency for Research on Cancer, Lyon, France; Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy; and Nutritional Research, Umea, Sweden). Weight change in later life and risk of death amongst the elderly: the European Prospective Investigation into Cancer and Nutrition-Elderly Network on Ageing and Health study. J Intern Med 2010; 000: 000-000. Objective. Later life weight change and mortality amongst elders. Design. Nested case-control study. Setting. Six countries from the European Investigation into Cancer and nutrition - Elderly, Network on Ageing and Health. Subjects. A total of 1712 deceased (cases) and 4942 alive (controls) were selected from 34 239 participants, >/= 60 years at enrolment (1992-2000) who were followed-up until March 2007. Annual weight change was estimated as the weight difference from recruitment to the most distant from-date-of-death re-assessment, divided by the respective time. Outcome measures. Mortality in relation to weight change was examined using conditional logistic regression. Results. Weight loss >1 kg year(-1) was associated with statistically significant increased death risk (OR = 1.65; 95% CI: 1.41-1.92) compared to minimal weight change (+/-1 kg year(-1)). Weight gain >1 kg year(-1) was also associated with increased risk of death (OR = 1.15; 95% CI: 0.98-1.37), but this was evident and statistically significant only amongst overweight/obese (OR = 1.55; 95% CI: 1.17-2.05). In analyses by time interval since weight re-assessment, the association of mortality with weight loss was stronger for the interval proximal (

Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r2 cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk. © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

Background: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. Objective: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. Design: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. Results: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. Conclusions: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of somefood intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases. © 2009 American Society for Nutrition.

BACKGROUND: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). PATIENTS AND METHODS: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). RESULTS: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55. Mortality data for The Netherlands were obtained from ‘Statistics Netherlands’. This paper was made possible by a grant of the European Community (5th Framework Programme) to PV (grant QLK4CT199900927) and a grant of the Compagnia di San Paolo to the ISI Foundation, and a grant of the EC to the ECNIS Network of Excellence (grant FOOD-CT-2005-513943)(WP4-8). All authors are independent from funders. Also, the work described in the paper was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO); ISCIII, Red de Centros RCESP, C03/09; Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Cancer Research, UK; Medical Research Council, UK; Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; Wellcome Trust, UK; Greek Ministry of Education; Italian Association for Research on Cancer; Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skåne, Sweden; Norwegian Cancer Society.

OBJECTIVE: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related to protein intake (P(trend)

Introduction Les troubles fonctionnels gastro-intestinaux telles que la diarrhee ou la constipation refletent un dysfonctionnement de la flore intestinale et ont deja ete associes a l’obesite ou certaines pathologies auto-immunes. Cependant peu d’etudes se sont focalisees sur le risque de diabete de type 2 (DT2). Materiels et methodes A partir de 62 683 femmes de la cohorte prospective E3N, nous avons etudie l’influence de la diarrhee, constipation et alternance diarrhee-constipation sur le risque de DT2. Nous avons egalement mis en place une modelisation de l’evolution de la frequence de ces troubles avant et apres le diagnostic de DT2 sur une fenetre d’observation de 25 ans. Resultats Un total de 1 795 cas de DT2 a ete recense entre 1993 et 2008. Par rapport aux femmes ayant un transit normal, celles declarant des diarrhees chroniques ou une alternance diarrhee-constipation avaient une augmentation de risque de DT2 (respectivement RR = 1,29 IC 95 %: [1,00-1,65] and 1,32 IC 95 %: [1,15-1,52]). En revanche, les femmes ayant une constipation chronique presentaient une diminution du risque de DT2 (RR = 0,67 IC 95 %: [0,57-0,78]). Ces associations persistaient lorsque l’on ajustait egalement sur l’indice de masse corporelle, sauf pour la diarrhee. Par rapport au diagnostic de DT2, nous avons observe une augmentation marquee de la frequence de diarrhee post-diagnostic, alors que l’opposee a ete observee pour la constipation. La frequence alternance diarrhee-constipation etait stable avant et apres le diagnostic. Conclusion Nos resultats sont en faveur d’un role de la flore intestinale sur le metabolisme du glucose, et encouragent a davantage d’investigations. Le controle des troubles intestinaux devrait s’inscrire dans la pratique clinique courante dans le cadre de la prevention du diabete. Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process. © 2006 Oxford University Press.

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Δ4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids –the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23–2.33), androstenedione 1.94 (1.40–2.69), testosterone 1.85 (1.33–2.57) and free testosterone 2.50 (1.76–3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42–3.02), oestradiol 2.28 (1.61–3.23) and free oestradiol (odds ratios 2.13 (1.52–2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

Objectives To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. Design Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC). Participants 303 020 people from the EPIC cohort (total 500 000) who had never smoked or who had stopped smoking for at least 10 years, 123 479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment. Main outcome measures Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. Results Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours). Conclusions This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.

IntroductionUne forte corpulence dans l’enfance ou l’adolescence pourrait influencer le risque de dépression chez l’adulte indépendamment de l’indice de masse corporelle à l’âge adulte [1,2]. Notre objectif était d’identifier chez des femmes françaises post-ménopausées l’association entre la corpulence à la naissance, dans l’enfance et au cours des premières années de vie adulte et le risque de dépression. MethodsAu sein de la cohorte E3N, 41 144 femmes ont renseigné leur poids et taille de naissance ainsi que la silhouette de Sørensen [3] qui correspondait le mieux à leur silhouette à 8 ans, à la puberté, à 20–25 ans et 35–40 ans. Des trajectoires représentant l’évolution de la silhouette au cours du temps ont été estimées grâce à un modèle à classes latentes (Fig. 1). Des modèles logistiques multinomiaux multi-ajustés ont ensuite permis d’estimer les associations entre ces facteurs et la dépression définie par l’échelle CES-D (CES-D ≥ 23), classée en dépression récurrente ou primo-incidente selon l’existence ou non d’un antécédent de trouble psychologique traité. Fig. 1Trajectoires de corpulence au cours de la vie, étude E3N (n = 41 144).RésultatsLe risque de dépression primo-incidente était plus élevé chez les femmes dont le poids de naissance était élevé, comparées à celles ayant un poids de naissance moyen (OR = 1,16 ; 95 % IC 1,01–1,34), mais aussi chez celles dont la corpulence était élevée tout au long de la vie, comparées à celles dont la corpulence restait faible (OR = 1,49 ; 95 % IC 1,22–1,80). Inversement, la dépression récurrente était associée à un poids de naissance faible (OR = 1,22 ; 95 % IC 1,05–1,41) et à la trajectoire correspondant à une augmentation de la corpulence entre 8 ans et la puberté puis à sa stabilisation (OR = 1,27 ; 95 % IC 1,03–1,56). ConclusionLe risque de dépression à l’âge adulte était associé à la corpulence à la naissance et à l’évolution de la corpulence au cours de la vie mais différait selon le caractère primo-incident ou récurrent de la dépression.