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The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery.This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects.This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL20 copies/mL, all with a BMI40 kg/m2 or35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology.The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively).HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.

International audience; Aim: To examine the association between antidepressant medication use and the risk of type 2 diabetes. Methods: Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. Results: Of the 63 999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. Conclusion: Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).

Background Previous case-control and cross-sectional studies have suggested that migraine is associated with an increased likelihood of dyslipidaemia, but it is uncertain if these associations are driven by lifestyle factors such as weight and exercise. This study aimed to explore cross-sectional associations between migraine and dyslipidaemia, whilst controlling for multiple potential confounders, including BMI and physical activity. Methods We included 71,582 women from the E3N study, who had provided information on migraine and dyslipidaemia in questionnaires. Dyslipidaemia and migraine were based on self-reports. Logistic regression models were used to assess the association between migraine and prevalent dyslipidaemia, controlling for potential confounders including BMI. As a sensitivity analysis, only dyslipidaemia cases with reimbursement for lipid-lowering medications were considered valid. Results Women were at a mean age of 70.9 years at inclusion. Dyslipidaemia was reported by 32,271 women and were reimbursed for lipid-lowering medications in 71.1% (n = 22,919) of cases. History of migraine was reported by 19,589 women. In unadjusted models, ever history of all migraine was not associated with the odds of dyslipidaemia (OR migraine = 1.01 [0.98: 1.05], p = 0.41), but this association was positive after adjusting for potential confounding factors such as age, BMI, and physical activity (OR migraine = 1.04 [1.01: 1.08], p = 0.02) and was consistent when considering only treated dyslipidaemia (OR migraine = 1.04 [1.00: 1.08], p = 0.03). Conclusions Migraine was associated with an increase in likelihood of dyslipidaemia, regardless of BMI and physical activity. Key messages Migraine is a disease with high prevalence in women. History of migraine is associated with an increased risk of dyslipidaemia.

Background During the past decades, human diet has evolved towards higher intakes of processed and ultraprocessed food. We have investigated the association between these food groups and the risk of inflammatory bowel disease (IBD) in the European Prospective Investigation into Cancer and Nutrition. Methods 413 590 participants from 8 European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. All EPIC food items were expressed as g/day and categorized according to the NOVA classification: “group 1—unprocessed or minimally processed foods”; “group 2—processed culinary ingredients”; “group 3—processed foods”; and “group 4—ultra-processed foods (UPFs)”. Because the EPIC dietary questionnaires were conceived before the NOVA classification, the food items were retrospectively categorized into this classification. Some food items collected in the EPIC questionnaires were difficult to categorize into group 3 or 4. We therefore merged them into a single category. We tested three scenarios for the estimation of the dietary content of this merged category: lower, middle and upper contents of groups 3 + 4. The association between the proportion of each NOVA group in the diet and IBD were estimated using Cox proportional hazard models to obtain Hazards Ratios (HRs) and 95% confidence intervals. We adjusted the HR for smoking status, educational level, physical activity, BMI, alcohol consumption and energy intake and stratified by centre, age at baseline (1-y interval), and sex. Results After a mean follow-up of 16 years, 179 Crohn’s disease (CD) and 431 ulcerative colitis (UC) cases were identified. NOVA group 1 was negatively associated with CD risk (adjusted HR for the fourth vs. the first quartile = 0.58; 95% CI = 0.35–0.95; P-trend = 0.03). Within group 1, fruit intake was the only food item to be negatively associated with the risk of IBD (adjusted HR for the fourth vs. the first quartile = 0.42; 95% CI = 0.24–0.73; P-trend = 0.003). We found numerical associations between group 3 + 4 and the risk of CD with the middle or upper scenarios (adjusted HRs for the fourth vs. the first quartile = 1.50; 95% CI = 0.92–2.46; P-trend = 0.12 and 1.41; 95% CI = 0.88–2.27; P-trend = 0.09 respectively). There was no association between any category of the NOVA classification and UC risk. Conclusion In the EPIC cohort, consumption of non-processed food was associated with a lower risk of CD while consumptions of processed or ultra-processed food were numerically associated with increased risk of CD. We found no association with UC.

This abstract was withdrawn by the authors. Citation Format: Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O'Brien KM, Adami H-O, Baglietto L, Bernstein L, Bertrand KA, Boutron-Ruault M-C, Chen Y, Connor AE, Dorronsoro M, Dossus L, Eliassen AH, Giles GG, Gram IT, Hankinson SE, Kaaks R, Key TJ, Kirsh VA, Kitahara CM, Koh W-P, Larsson SC, Linet MS, Ma H, Masala G, Merritt MA, Milne RL, Overvad K, Ozasa K, Palmer JR, Riboli E, Rohan TE, Sadakane A, Sund M, Tamimi RM, Trichopoulou A, Ursin G, Van Gils CH, Visvanathan K, Weiderpass E, Willett WC, Wolk A, Yuan J-M, Zeleniuch-Jacquotte A, Sandler DP, Swerdlow AJ. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-01.

This abstract was withdrawn by the authors. Citation Format: Veron L, Gelot A, Gusto G, Arveux P, Delaloge S, Boutron-Ruault M-C. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-05.

BackgroundRheumatoid arthritis (RA) is an inflammatory rheumatic disease of multifactorial aetiology, which preferentially affects women. To date, active personal smoking has been the most reproducibly reported risk factor for anti-citrullinated protein antibodies (ACPA) positive RA. Fish consumption has been thought to reduce the risk of rheumatoid arthritis (RA), but reported data were conflicting.ObjectivesTo assess the association between fish consumption (overall, lean fish, and oily fish) and the risk of RA.MethodsThe E3N study (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale) is a French prospective cohort investigating environmental factors associated with chronic diseases. It follows 98,995 healthy French women since 1990 covered by a national health insurance primarily involving teachers. RA cases have been previously identified with specific questionnaires and medication reimbursement database. Dietary data were collected via a validated food-frequency questionnaire in 1993. Cox proportional hazards models were used to calculate HRs and 95% CIs for incident RA depending on the tertiles of consumption of overall, lean and oily fish. Models were adjusted for age and for the main potential confounders. Stratified analyses were conducted depending on the active smoking status (never or ever-smoker).ResultsAmong 62,629 women, 480 incident cases of RA were identified. In the overall population, we did not find a linear association between overall fish consumption and RA risk (p for trend 0.65), but a moderate consumption of fish (16.7−31.1 g/day, roughly corresponding to 1 to 2 servings a week) was associated with a decreased risk of RA (HR 0.74; 95% CI 0.59—0.94 for tertile 2 compared with tertile 1), especially among ever smoking women (HR 0.61; 95% CI 0.44—0.85). Although not statistically significant, a trend towards an inverse association was only found with oily fish consumption (HR 0.81; 95% CI 0.65—1.02 for tertile 2), but not with lean fish.ConclusionIn our large population-based cohort study of French women, there was a U-shaped relationship between overall fish consumption and the risk of RA, with a reduced RA risk only in moderate consumers. The inverse association was restricted to ever-smokers. When separately considering oily and lean fish, the second tertile of oily fish consumption was inversely associated with the risk of RA only in never-smokers, while there was no association with lean fish.Table 1.Hazard ratios (95% confidence intervals) for the risk of rheumatoid arthritis (RA) by tertiles of fish consumption (N = 62,629)Fish consumptionNon-cases N (%)RA N (%)Model 1 HR (95% CI)Model 2 HR (95% CI)All populationN=62,149N=480 Tertile 1 (0−16.7 g/day)20,509 (33.00)172 (35.83)ReferenceReference Tertile 2 (16.7−31.1 g/day)19,628 (31.58)121 (25.21)0.74 [0.58; 0.93]0.74 [0.59; 0.94] Tertile 3 (31.1−261 g/day)22,012 (35.42)187 (38.96)0.99 [0.80; 1.22]0.99 [0.80; 1.22] Ptrend0.630.65Never smokersN=33,314N=244 Tertile 1 (0−16.7 g/day)11,322 (33.99)79 (32.38)ReferenceReference Tertile 2 (16.7−31.1 g/day)10,556 (31.69)66 (27.05)0.89 [0.64; 1.24]0.90 [0.65; 1.25] Tertile 3 (31.1−261 g/day)11,436 (34.33)99 (40.57)1.19 [0.88; 1.60]1.21 [0.90; 1.64] Ptrend0.150.12Ever smokersN=28,835N=236 Tertile 1 (0−16.7 g/day)9,187 (31.86)93 (39.41)ReferenceReference Tertile 2 (16.7−31.1 g/day)9,072 (31.46)55 (23.31)0.60 [0.43; 0.84]0.61 [0.44;0.85] Tertile 3 (31.1−261 g/day)10,576 (36.68)88 (37.29)0.81 [0.60; 1.09]0.81 [0.60; 1.08] Ptrend0.390.36M1: Adjusted for total daily intake and ageM2: M1+ body mass index (kg/m2), smoking status (current smoker, non-smoker, former smoker, except for stratified analyses), passive smoking in childhood (no, yes), gastrointestinal transit (normal, diarrhoea, constipation, alternating diarrhoea/constipation), educational level (< High School, up to 2-level university, 3-4 level university), and physical activity (in quartiles)Disclosure of InterestsNone declared

BackgroundGiant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two associated inflammatory diseases with incompletely known common pathophysiological mechanism. Cardiovascular (CV) risk factors have been thought to play a role in the underlying chronic vascular inflammation involved in GCA and PMR pathophysiology. However, available data on CV risk factors are conflicting.ObjectivesTo investigate the association between CV risk factors and the risk of GCA and/or PMR in a large prospective cohort of French women.MethodsThe E3N cohort study (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale) is a French prospective cohort including 98,995 French women born between 1925 and 1950, recruited in 1990. They completed biennially mailed questionnaires to update their health-related information. A validation study based on the use of a specific GCA/PMR questionnaire and medication reimbursement database was conducted prior to this study. The history of CV risk factors (hypertension, type 2 diabetes, dyslipidemia, active smoking status and family history of cardiovascular disease) was self-reported at each questionnaire. Hazard ratios (HRs) and their 95% confidence intervals (95%CIs) for incident GCA and/or PMR were estimated by Cox proportional hazards regression models with age as the time scale. Multi-adjusted models included all CV risk factors and educational level. Further analyses were conducted to separately analyse the risk of incident GCA and of PMR.ResultsThe overall population included 79,804 women, during a total follow-up of 1,899,742 person-years. Among them, 399 incident GCA and/or PMR cases were identified (incidence 31/100,000 person-years): 282 PMR alone, 112 GCA cases, and 5 patients who could not be classified. Incident GCA/PMR cases were diagnosed after a mean of 17.9 (± 5.2) years after recruitment. Mean age at diagnosis was 69 (± 7.2) years. Type 2 diabetes was inversely associated with risk of incident GCA/PMR in age-adjusted and multivariable models (HR 0.41; 95%CI 0.2–0.9 in multivariate model). Other CV risk factors such as hypertension, smoking status, dyslipidaemia, familial history of cardiovascular events were not associated with incident GCA/PMR (Table 1). The inverse association remained statistically significant when studying separately the risk of incident PMR (HR 0.3; 95%CI 0.09–0.91) but no longer with incident GCA (HR 0.5; 95%CI 0.1–2.0), probably due to a reduced statistical power.Table 1.Hazard ratios for the risk incident GCA and/or PMR according to cardiovascular risk factorsNON-CASESN=79,405GCA/PMRCASESN=399M1M2Number (%)Number (%)HR [95%CI]HR [95%CI]Smoking status Never-smoker42,2745 (53.2)233 (58.4)ReferenceReference Past smoker30,824 (38.8)134 (33.6)0.91 [0.74;1.13]0.90 [0.73; 1.12] Current smoker6,307(7.9)32 (8.0)1.05 [0.72; 1.52]1.04 [0.72; 1.51]High-blood pressure No hypertension38,813 (48.9)210 (52.6)ReferenceReference Hypertension40,592 (51.1)189 (47.4)0.84 [0.89; 1.03]0.85 [0.69; 1.04]Type 2 diabetes No diabetes75,704 (95.3)386 (96.7)ReferenceReference Diabetes3,701 (4.7)13 (3.3)0.41 [0.18; 0.91]0.41 [0.18; 0.92]BMI 52,054 (65.6)269 (67.4)ReferenceReference ≥ 25 kg/m227,351 (34.4)130 (32.6)1.01 [0.82; 1.25]1.06 [0.85; 1.31]Dyslipidemia No43,944 (55.3)237 (59.4)ReferenceReference Yes33,169 (41.8)147 (36.8)1.17 [0.94; 1.44]1.18 [0.95; 1.45]Familial history of cardiovascular disease No64,878 (81.7)336 (84.2)ReferenceNA Yes3,121 (3.9)20 (5.0)1.30 [0.85; 2.09]NAM1: Adjusted for age and educational level educational level ( 3 years of university),M2: M1+ smoking status, body mass index(kg/m2), hypertension, diabetes, dyslipidemiaConclusionType 2 diabetes was associated with a decreased risk of subsequent GCA/PMR development. Further work should be carried out to determine potential mechanisms, and especially to analyze the respective role of diabetes itself and its treatments.AcknowledgementsThe authors are indebted to all participants for their continued participation. The authors would like to thank Pascale Gerbouin-Rerolle, Mariam Alyaniakian, Sofiane Harizi and Roselyn Rima Gomes for their help on data management. The present work was performed using data from the Inserm E3N cohort and support from the MGEN, Gustave Roussy, and the Ligue contre le Cancer for setting up and maintaining the cohort. The cohort was supported by a state grant ANR-10-COHO-0006 from the Agence Nationale de la Recherche within the Investissement d’Avenir program. The present work was conducted thanks to a research grant from the Agence Régionale de Santé – Île de France.ledgements to declare.Disclosure of InterestsNone declared

BackgroundGiant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two associated inflammatory diseases that probably share common pathophysiological mechanisms. Data on environmental risk factors are lacking. Population based cohort studies are the most adequate and less biased sources for identifying such factors. But case validation of disease diagnoses is the first necessary step for running such studies, even though it is not easy to perform.ObjectivesTo assess the accuracy of self-reported GCA/PMR diagnoses and to develop algorithms to ascertain GCA/PMR in a large French population-based cohort, using combined data of a dedicated questionnaire and medication reimbursement database.MethodsThe E3N cohort study (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale) includes 98,995 healthy French women born between 1925 and 1950, recruited in 1990 and was designed to investigate lifestyle and environmental factors associated with chronic conditions. Participants completed biennially mailed questionnaires to update their health-related information, lifestyle characteristics, and newly diagnosed diseases. Women who self-reported a diagnosis of GCA and/or PMR were sent a specific validation questionnaire designed to ascertain the diagnosis including clinical, biological, and therapeutic data, along with ACR 1990 classification criteria for GCA and ACR/EULAR 2012 classification criteria for PMR. We then devised algorithms based on self-reported answers and a medication reimbursement database, and evaluated their accuracy, comparing them with diagnoses obtained from medical chart review.ResultsAmong the 98,995 participants, 1,392 women self-reported GCA/PMR. The specific questionnaire was sent to 1,143 (82.1%) of the eligible women (249 women could not be contacted because of death or withdrawn consent) and response was obtained for 830 women (59.6%). Among them, 202 women provided sufficient medical data to ascertain a diagnosis and study accuracy of developed algorithms. 56 women were classified as ACG and 121 as PMR. Self-reported diagnoses alone had an accuracy of 87.6% with medical chart review. If women additionally self-reported a diagnosis confirmation by a physician and the use of glucocorticoids for ≥ 3 months, the accuracy was improved to 89.9%. For patients who did not respond to validation questionnaire, adding the use of glucocorticoids for ≥ 3 months in the reimbursement database also improved the diagnosis accuracy to 92.8%. These two designed algorithms also had the benefit of reducing the number of false positive cases by 10 and 16 respectively. Finally, 589 GCA and/or PMR cases were confirmed by our two devised algorithms: 401 cases with algorithm using the specific GCA/PMR questionnaire and 188 with medication reimbursement database. The mean age at diagnosis was 70.3 (± 8.0) years [73.4 (± 6.2) years for cases detected using the specific GCA/PMR questionnaire and 68.9 (± 8.3) years for cases detected with medication reimbursement database]. Demographic and clinical data were similar between our population of validated cases by medical chart review and the cases detected by our algorithms in the cohort.ConclusionThe accuracy of self-reported diagnosis of GCA/PMR was high in the E3N-cohort. Using additional data such as medication reimbursement and/or other self-reported data from a specific questionnaire, particularly the prolonged use of glucocorticoids led to a better accuracy with a very small number of false positive cases and seemed to be sufficient to correctly ascertained GCA and/or PMR diagnoses. With the validation of nearly 600 GCA and/or PMR cases in our cohort, we will be able to conduct epidemiological studies to identify risk factors of these diseases.AcknowledgementsThe authors are indebted to all participants for their continued participation. The authors would like to thank Pascale Gerbouin-Rerolle, Mariam Alyaniakian, Sofiane Harizi and Roselyn Rima Gomes for their help on data management. The present work was performed using data from the Inserm E3N cohort and support from the MGEN, Gustave Roussy, and the Ligue contre le Cancer for setting up and maintaining the cohort. The cohort was supported by a state grant ANR-10-COHO-0006 from the Agence Nationale de la Recherche within the Investissement d’Avenir program. The present work was conducted thanks to a research grant from the Agence Régionale de Santé – Île de France.Disclosure of InterestsNone declared

BackgroundThe role of nutrition in the pathogenesis of RA has been suggested in many studies but remains controversial.ObjectivesTo assess the relationship between consumption of the most frequently drinked specific beverages (coffee, tea, alcohol, and soft drinks) and the risk of RA.MethodsThe E3N Study (Étude Épidémiologique auprès des femmes de la Mutuelle Générale de l’Éducation Nationale) is a French prospective cohort including 98,995 women since 1990. RA cases have been previously identified with specific questionnaires and medication reimbursement database (1). Food and beverage consumption was assessed using a validated food-frequency questionnaire. Hazard ratios (HR) and their 95% confidence intervals (CI) for incident RA were estimated by Cox proportional hazards models, adjusted for age and the main potential confounders, including smoking. Tests for linear trends were performed. As smoking is a major risk factor for RA, stratified analyses were conducted according to the smoking status (ever or never-smoker) even in the absence of statistically significant interaction between the smoking status and beverage consumptions. Sensitivity analyses were performed in the subgroup of seropositive cases (positive RF and/or ACPA).ResultsDuring a total follow-up of 21 years (mean 20.78 (SD 2.26) years), 62,630 women contributed 1,300,874 person-years, and 481 developed RA (incidence 37/100 000 person-years). Incident RA cases were diagnosed a mean 11.7 (SD 5.9) years after baseline. Of the 179 (37.2%) RA cases with known antibody status, 153 (31.8%) were seropositive. Consumptions of total alcohol, tea and sugar-sweetened soft drinks were not associated with RA risk. Coffee consumption was associated with RA risk with a dose-effect relationship (≥4 cups/day versus ≤ 1cup/day, HR 1.24, 95% CI [0.94; 1.64], ptrend = 0.04), only in never-smokers. According to the type of coffee consumed, only high caffeinated coffee consumption was associated with an increased risk of RA among never-smokers (≥ 3.5 cups/day versus ≤ 1 cup/day, HR=1.62 95% CI [1.12;2.34], ptrend = 0.006, pinteraction = 0.07). Decaffeinated coffee consumption was not associated with RA risk. Risk of RA was higher with artificially-sweetened soft-drinks consumption (consumers versus non-consumers, HR 1.66 [1.12; 2.45]), in never-smokers. No association was observed with other soft drinks. Moderate liquor (spirits or aperitifs) intake was associated with a reduced risk of RA among ever-smokers (consumption of 1 - 3 glasses/week versus non-consumers HR 0.63, 95% CI [0.43; 0.91]) and moderate wine consumption was associated with a decreased risk of seropositive RA (consumption of 4 -10 glasses/week versus ≤ 1glass/week HR 0.57, 95% CI [0.35 to 0.94], whereas no association was observed with other alcohols.ConclusionConsumptions of tea, total alcohol, and sugar-sweetened soft drinks were not associated with RA risk, whereas consumptions of coffee (especially caffeinated coffee), and artificially-sweetened soft drinks were associated with higher RA risk, among never-smokers. By contrast, moderate liquor consumption was associated with a decreased risk of RA in ever-smokers, and moderate wine consumption was associated with a decreased risk of seropositive RA. If further confirmed, these results could lead to novel mechanistic hypotheses and to simple prevention measures.References[1]Nguyen Y, Salliot C, Gusto G, Descamps E, Mariette X, Boutron-Ruault M-C, et al. Improving accuracy of self-reported diagnoses of rheumatoid arthritis in the French prospective E3N-EPIC cohort: a validation study. BMJ Open. d caffeinated coffee),AcknowledgementsThe authors would like to thank Pascale Gerbouin-Rerolle, Mariam Alyaniakian, Sofiane Harizi and Roselyn Rima Gomes for their help on data management. The present work was performed using data from the Inserm E3N cohort and support from the MGEN, Gustave Roussy, and the Ligue contre le Cancer for setting up and maintaining the cohort. The cohort was supported by a state grant ANR-10-COHO-0006 from the Agence Nationale de la Recherche within the Investissement d’Avenir program.The present work was conducted thanks to a research grant from the Société Française de Rhumatologie.Disclosure of InterestsNone declared

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between oral contraceptive (OC) use and melanoma risk. However, findings were conflicting and data from large prospective studies are lacking. E3N is a prospective cohort of 98,995 French women aged 40-65 years at inclusion in 1990. Exposure to lifetime OC use was assessed in 1992 and through biennial questionnaire updates. To assess the association between OC use and melanoma risk, we used Cox models adjusted for age, pigmentary traits, residential ultraviolet (UV) exposure in county of birth and at inclusion and family history of skin cancer. Over 1992-2008, 539 melanoma cases were ascertained among 79,365 women. In age-adjusted models, we found a modest positive association between ever use of OCs and melanoma risk (hazard ratio (HR) = 1.18, 95% confidence intervals (CIs) = 0.98-1.42), which was reduced after adjustment (HR = 1.14, 95% CI = 0.95-1.38). The association was stronger in long-term users (duration ≥10 years: HR = 1.33, 95% CI = 1.00-1.75) and in women who used high-estrogen OCs (HR = 1.27, 95% CI = 1.04-1.56). Among users, there was an inverse association with age at first use (ptrend < 0.01), but no evidence of an association with age at last use or time since last use. OC use was positively associated with tanning bed use (OR = 1.14, CI = 1.01-1.29), sunburns (ptrend = 0.5) and sunscreen use (OR = 1.13, CI = 1.00-1.28) since age 25. Overall, our findings do not support a strong association between OC use and melanoma risk and suggest intentional UV exposure in OC users, which supports a potential confusion by UV exposure in this relationship.

International audience; AimsTo identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk.MethodsBetween 1995 and 2014, we followed 402 women from the E3N cohort study who were considered to be at very high risk of Type 2 diabetes based on the D.E.S.I.R. score. We then computed a classification and regression tree model to identify, among a large set of risk factors, the top risk factors associated with not having Type 2 diabetes at the end of the follow‐up.ResultsDuring follow‐up, 117 women (29%) were diagnosed with Type 2 diabetes, while 285 (71%) were still free of the disease in 2014. A low Western dietary pattern score was the top characteristic associated with not developing Type 2 diabetes, as only 20% of the women at very high risk in the E3N study with that characteristic developed Type 2 diabetes (compared with 29% overall). In women with a moderate or high Western dietary pattern score, the most important characteristic associated with not developing Type 2 diabetes was a high total dietary antioxidant capacity, as only 26% of these women ultimately developed Type 2 diabetes.ConclusionsWe showed that the top characteristic associated with not developing Type 2 diabetes, despite being at very high risk, was a healthy diet, characterized by limiting Western dietary habits, but with a high intake of antioxidant‐rich foods. This underscores the importance of diet in the prevention of Type 2 diabetes in people at high risk.

Introduction L’implication des hormones feminines endogenes et exogenes sur le risque de developper une polyarthrite rhumatoide (PR) est vraisemblable au vu de taux d’incidence plus eleves chez la femme que chez l’homme, de l’augmentation des incidences en post-partum et apres la menopause. Cependant les donnees de la litterature concernant l’association entre facteurs de reproduction (analyses individuellement) et PR sont discordantes. Notre objectif etait d’evaluer l’association entre les durees et niveaux d’expositions hormonales, tout au long de la vie d’une femme, et le risque de PR. Patients et methodes La cohorte francaise E3 N (« Etude Epidemiologique aupres de femmes de la Mutuelle Generale de l’Education Nationale ») a inclus 98 995 femmes, suivies prospectivement depuis 1990 a l’aide de questionnaires portant sur leurs donnees demographiques, leur mode de vie, et leurs donnees de sante. Parmi elles, 698 ont developpees une PR incidentes dont le diagnostic a ete validees par une etude specifique [1] . L’âge a la menarche, l’âge a la menopause, les durees cumulees des traitements hormonaux (contraception orale [CO] et traitement hormonal de la menopause [THM]) et de l’allaitement, le nombre de grossesses ont ete collectes regulierement cours du suivi. Les expositions aux hormones feminines etaient definies comme suit : – La duree de vie fertile = nombre d’annees entre la menarche et la menopause ; – Le nombre total d’annees d’ovulation (variable dependante du temps) = duree de vie fertile–(nombre de grossesses menees a terme x 0,75 + nombre de fausses-couches x 0,25 + duree totale de l’allaitement + duree totale de la CO) ; – La duree totale de l’exposition hormonale endogene et exogene (en annees, dependant du temps) = duree de vie fertile + duree totale du THM ; – Le score composite d’exposition aux œstrogenes (CES) variant de 0 a 5 : calcule en assignant 1 point pour menarche precoce (≤ 10 ans), parite elevee (> 3 grossesses), antecedent d’hysterectomie, la prise de traitement hormonaux (CO et/ou THM) et/ou menopause tardive (≥ 53 ans). Les Hazard Ratios (HRs) et leurs intervalles de confiance a 95 % (IC95 %) ont ete estimes par des modeles de Cox, avec l’âge en echelle de temps. Les modeles ont ete ajustes sur l’âge (modele 1) puis multi-ajustes sur le tabagisme actif, le tabagisme passif, le niveau d’etude, l’indice de masse corporelle et certains facteurs de reproduction (modele 2). Resultats Parmi 78391 femmes menopausees, 637 PR sont survenues, pour un total de 1 864,915 femmes-annees. Quel que soit le modele, la duree de vie fertile, le nombre total d’annees d’ovulation et la duree totale d’exposition hormonale n’etaient pas significativement associes au risque de PR (p de tendance : p = 0,25, p = 0,43, p = 0,92, respectivement [modele 1]). Dans le modele multi-ajuste (modele 2), un niveau eleve d’exposition aux œstrogenes (CES = 3-5) etait inversement associe au risque de PR : HR = 0,65 (IC95 0,4–0,9), p = 0,04, comparativement au niveau faible (CES = 0-1). Dans une publication recente, un niveau eleve d’exposition aux œstrogenes etait egalement associe a une diminution du risque de syndrome de Sjogren primaire [2] . Conclusion Dans la cohorte E3 N, un niveau d’exposition eleve aux œstrogenes au cours de la vie est associe a une diminution du risque de PR apres la menopause.

STUDY QUESTION Are body size across the life course and adult height associated with endometriosis? SUMMARY ANSWER Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height. WHAT IS KNOWN ALREADY The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis. STUDY DESIGN, SIZE, DURATION We used a nested case-control design within E3N (Etude Epidemiologique aupres de femmes de l'Education Nationale), a prospective cohort of French women. Data were updated every 2-3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women. MAIN RESULTS AND THE ROLE OF CHANCE The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20-25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vit ...

Introduction et but de l’etude La repetition d’episodes inflammatoires de plusieurs origines (virales, alcooliques, metaboliques) conduisant a la cirrhose sont sans doute des causes majeures de carcinogenese hepatique. La relation entre alimentation et carcinome hepatocellulaire (CHC) sur cirrhose a encore ete peu exploree. Notre objectif etait d’examiner l’association entre le potentiel inflammatoire de l’alimentation (evalue par Dietary Inflammatory Index, DII) et le risque de CHC chez des patients cirrhotiques. Materiel et methodes Dans l’etude multicentrique CiRCE (Cirrhose et Risque de Carcinome hepatocellulaire dans le grand Est), 181 patients cirrhotiques avec CHC (cas) et 401 patients cirrhotiques sans CHC a l’inclusion (temoins), ont ete recrutes entre 2008 et 2012, dans 6 hopitaux de l’Est de la France. Les scores du DII, calcules a partir de la consommation de 36 composants evaluee par questionnaire type histoire alimentaire, ont ete categorises en tertiles. Les Odds Ratio (OR) et intervalles de confiance a 95 % etaient obtenus par regression logistique non conditionnelle multivariee. Resultats et analyse statistique Les scores du DII variaient entre −4,77 et 7,59 avec une valeur moyenne de 1,03 ± 2,87 chez les 181 cas et de 0,83 ± 2,87 chez les 401 temoins, indiquant un regime pro-inflammatoire dans les deux groupes. Apres ajustement, une association statistiquement significative etait mise en evidence entre une alimentation pro-inflammatoire (DII positif) et le risque de developper un CHC, en considerant le DII en continue (OR = 1,14 [1,02–1,27], p = 0,021) ou en tertiles (ORt3vst1 = 2,33 [1,16–4,67], p-tendance = 0,021). Des resultats similaires ont ete obtenus lorsque l’alcool etait retire du calcul du DII mais inclus comme variable d’ajustement : DII en continu (OR = 1,15 [1,03–1,28], p = 0,013) et DII en tertile (ORt3vst1 = 2,35 [1,18–4,68], p-tendance = 0,015). Conclusion Les patients cirrhotiques ayant une alimentation plutot pro-inflammatoire etaient plus a risque de developper un CHC. Nos resultats devront etre confirmes en prospectif et sur un plus large echantillon.

Purpose:Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5years of follow-up. Methods:A total of 255,170 participants aged 25–70years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. Results:A one-SD increment in CEL intake was associated with 0.111kg (95% CI 0.087–0.135) additional weight gain over 5years. The corresponding additional weight gain for CML and MG-H1 was 0.065kg (0.041–0.089) and 0.034kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. Conclusion:In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5years of follow-up.

Background:Rheumatoid arthritis (RA) is a systemic autoimmune disease of multifactorial aetiology, which preferentially affects women. To date, active smoking has been the most reproducibly reported risk factor for anti-citrullinated protein antibodies (ACPA) positive RA, particularly persons who carry the HLA-DRB1-shared epitope (SE) alleles.Objectives:We aimed to investigate the relationships between passive smoking in childhood (PSc) or in adulthood (PSa), and the risk of incident RA in a large prospective cohort of healthy French women.Methods:The E3N-EPIC (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale) is a French prospective cohort study that investigates environmental factors associated with chronic diseases. It follows 98,995 healthy French women since 1990 covered by a national health insurance primarily involving teachers. RA cases have been previously identified with specific questionnaires and medication reimbursement database. Women were considered exposed to PSc if they self-declared staying in a smoky room several hours a day during childhood, and to PSa if they self-declared being exposed at least one hour a day to passive smoking while adults. We used Cox multivariable regression models with age as the timescale (model 1), adjusted on smoking status (never, current, or former smoker) and on the two types of passive smoking (model 2), and on educational level, and BMI (model 3). Stratified analyses were conducted depending on the active smoking status (never or ever-smoker).Results:79,806 women were included in the study. Mean (± SD) age at cohort entry was 49.0 (± 6.4) years. Among them, 698 incident RA cases were identified, diagnosed after a mean of 11.7 (± 5.8) years after baseline. In the whole cohort, 10,810 (13.5%) women were exposed to PSc, 42,807 (53.6%) to PSa, 6,581 (8.25%) were exposed to both, and 47,036 (58.9%) were exposed to either.In the whole population, PSc was positively associated with the risk of RA in all three models (HR 1.24; 95% CI [1.01 to 1.51] in Model 3). In stratified analyses on smoking status, PSc was associated with RA among never-smoking women (HR 1.42; 95% CI [1.07 to 1.88]), but not among ever-smoking women (HR 1.10; 95% CI [0.83;1.46]).In the whole population, PSa was also positively associated with the risk of RA in all three models (HR 1.19; 95% CI [1.02 to 1.40] in Model 3). In stratified analyses on the smoking status, PSa was associated with an increased RA risk only among never-smoking women (HR 1.27; 95% CI [1.02 to 1.57]) and not among ever-smoking women (HR 1.16; 95% CI [0.93;1.44]).Conclusion:In this large population-based prospective cohort study of French women, we reported that passive exposure to smoking during childhood or adulthood increased the risk of RA. The association was principally observed among never smoking women. These results suggest that smoking by-products, whether actively or passively inhaled absorbed, could generate autoimmunity, at least towards antigens involved in RA pathogenesis.References:[1]Karlson EW, Chang S-C, Cui J, et al. Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis. Ann Rheum Dis 2010;69:54–60.[2]Seror R, Henry J, Gusto G, et al. PSc increases the risk of developing rheumatoid arthritis. Rheumatology 2019;58:1154–62.[3]Nguyen Y, Salliot C, Gusto G, et al. Improving accuracy of self-reported diagnoses of rheumatoid arthritis in the French prospective E3N-EPIC cohort: a validation study. BMJ Open 2019;9:e033536.Disclosure of Interests:None declared

Background:Several cohort and case-control studies have suggested that overweight or obesity is associated with the risk of Rheumatoid Arthritis (RA). Associations were based on Body Mass Index (BMI), although this measurement does not reflect the fat distribution [1].Objectives:To study the relationships between anthropometric measurements and the risk of RA in women involved in the E3N cohort.Methods:E3N is an ongoing French prospective cohort that enrolled 98,995 women aged 40-65 years in 1990. Women completed mailed questionnaires every 2-3 years on lifestyle and health-related information. A total of 698 incident RA cases have been validated among 78,452 women [2]. Available anthropometric measurements include birth height and weight, height and weight (collected at baseline and regularly updated during follow-up), and age-related body shapes (BS). Women had to identify the silhouette among 8 BS that best described their BS at 8 years, puberty, 20-25 years, 30-35 years, and study baseline. BS trajectories (from 8 to 30-35 years) were constructed using Nagin’s approach to group-based trajectory modeling that identifies 6 different trajectories [3]. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident RA were estimated using Cox proportional hazards regression models with age as the time scale. Models were first adjusted for known risk factors of RA (model 1), and then multi-adjusted (model 2).Results:Taking lean BS as reference, medium BS at puberty was associated with an increased risk of RA [HR=1.23 (95% CI 1.0-1.5)], in the fully adjusted model (table 1), as was large BS at baseline [HR =1.32 (95% CI 1.1-1.6)] (in model 1). Obesity (BMI>30 kg/m2) was marginally associated with RA in model 1 [HR=1.30 (95% CI 1.0-1.7)], but the association was no longer statistically significant in the multi-adjusted model, taking normal BMI [18-25 kg/m2[as the reference.Birth weight and height, BS (at 8, 20-25 and 30-35 years), and BS trajectories were not significantly associated with RA in any model.Conclusion:In E3N cohort, medium body shape at puberty was associated with an increased risk of RA independently of the BMI and smoking exposure.Table 1.Cox proportional-hazards analysis of anthropometric factors associated with RARANon-casesMODEL 1MODEL 2HRs (95%CI)ptrendHRs (95%CI)ptrendBaseline Body mass index (kg/m2)101,7970.75 (0.4-1.4)0.05320.85 (0.4-1.6)0.6165 [18-25[46250,330RefRef [25-30]17119,7161.10 (0.9-1.3)1.00 (0.8-1.2)> 30555,9111.30 (1.0-1.7)1.13 (0.8-1.6)Body shape at pubertyLean33240,485Ref0.0937Ref0.1490Medium17917,9031.24 (1.0-1.5)1.23 (1.0-1.5)Large14715,9841.14 (0.9-1.4)1.12 (0.9-1.4)Body shape at baselineLean35944,718Ref0.0055Ref0.1743Medium20020,0411.20 (1.0-1.4)1.16 (0.9-1.4)Large1109,8381.32 (1.1-1.6)1.20 (0.9-1.6)ptrend: p for trend. Ref: reference.Model 1 adjusted for age, smoking (past/current/never), passive smoking during childhood and/or adulthood (ever/never), educational level (Multi-adjusted model 2 included model 1 + body mass index (30 kg/m2), body shape at puberty, body shape at baseline adjusted for age, baseline physical activity (in quartiles), age at menarche (24 months).References:[1]Crowson CS, Matteson EL, Davis JM 3rd, Gabriel SE. Contribution of obesity to the rise in incidence of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65:71-7.[2]Nguyen Y, Salliot C, Gusto G, et al. Improving accuracy of self-reported diagnoses of rheumatoid arthritis in the French prospective E3N-EPIC cohort: a validation study. BMJ Open. 2019;9:e033536.[3]Nagin D. Analyzing developmental trajectories: a semiparametric, group based approach. Psychol Methods 1999;4:139e57.Disclosure of Interests:None declared

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

Background Diet may contribute to inflammatory bowel disease (IBD) pathogenesis. In a previous French cohort, we found an association between high protein intake and increased risk of IBD. We aimed to investigate this relationship in the EPIC-IBD (European Prospective Investigation into Cancer and Nutrition – Inflammatory Bowel Diseases) cohort. Methods 413 593 participants from 8 European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Mean daily intake of nutrients was assessed using the EPIC nutrient database. To reduce bias in the estimation of relative risks, calibrated dietary data were obtained from the country and sex-specific calibration models for all participants. Associations between proteins (total, animal, and vegetable) or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models. Results After a mean follow-up of 16 years, 595 incident cases of IBD were identified, including 177 Crohn’s disease (CD) and 418 ulcerative colitis (UC) cases. No association was observed between total protein intake and IBD risk (adjusted HR for the fourth vs. the first quartile = 1.25; CI 95% = 0.89–1.77, P-trend = 0.33). There was a significant association between the calibrated continuous variable of animal protein intake and IBD risk (adjusted HR per 10 g/day: 1.10; 95% CI = 1.004–1.21) although no association was found for extreme quartiles (HR: 0.99; 95% CI = 0.73–1.34; P-trend = 0.91). There was no association between vegetable protein intake and IBD risk. There was an association between meat consumption and IBD risk (adjusted HR for the fourth vs.. the first quartile = 1.37; CI95% = 1.02–1.82, P-trend = 0.003) and between red meat consumption and IBD risk (adjusted HR for the fourth vs. the first quartile = 1.41; CI95% = 1.03–1.92, P-trend = 0.006). In separate analyses for CD and UC, there was an association between total meat and UC risk, and between red meat and UC risk. No association was found between food sources of animal proteins and CD risk. Conclusion Animal protein intake is associated with IBD risk in the EPIC-IBD cohort. Observed associations between meat consumption and IBD or UC risk, and between red meat consumption and IBD or UC risk deserve further investigation.

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between menopausal hormone therapy (MHT) use and melanoma risk; however, previous findings were conflicting. We sought to explore the associations between MHT use and melanoma risk in a prospective cohort of women in France, where a particularly wide variety of MHT formulations are available. E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. MHT use was assessed through biennial self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and skin cancer risk factors. Over 1990-2008, 444 melanoma cases were ascertained among 75,523 postmenopausal women. Ever use of MHT was associated with a higher melanoma risk (hazard ratio (HR) = 1.35, 95% confidence intervals (CI) = 1.07-1.71). The association was strongest among past users (HR = 1.55, CI = 1.17-2.07, homogeneity for past vs. recent use: p = 0.11), and users of MHT containing norpregnane derivatives (HR = 1.59, CI = 1.11-2.27), although with no heterogeneity across types of MHT (p = 0.13). Among MHT users, the association was similar across durations of use. However, a higher risk was observed when treatment onset occurred shortly after menopause (6 months: HR = 1.55, CI = 1.16-2.07 vs. ≥2 years). Associations between MHT use and melanoma risk were similar after adjustment for UV exposure, although MHT users were more likely to report sunscreen use than nonusers. Our data do not support a strong association between MHT use and melanoma risk. Further investigation is needed to explore potential effect modification by UV exposure on this relationship.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from 375 incident pancreatic cancer cases and 375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval]=0.41-0.98; Ptrend =0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 =0.60; 95%CI=0.39-0.92; Ptrend =0.02) and docosapentaenoic acid (ORT3-T1 =0.52; 95%CI=0.32-0.85; Ptrend =0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 =3.00; 95%CI=1.13-7.99; Ptrend =0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 =0.37; 95%CI=0.17-0.81; Ptrend =0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 =3.40; 95%CI=1.39-8.34; Ptrend =0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking. This article is protected by copyright. All rights reserved.

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.

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends

Objectives To analyse the impact of active and passive smoking and intestinal transit disorders on the risk of incident RA Methods This study is based on the French E3N cohort (“Etude Epidemiologique aupres de femmes de l9Education Nationale”), which included 98,995 women volunteers born between 1925 and 1950 and prospectively followed since 1990. Eleven self-administered questionnaires were sent to the participants between 1990 and 2014 to collect medical, demographic, environmental and hormonal data and dietary habits. The diagnosis of RA was collected on 2 successive questionnaires. Cases were considered certain if having declared RA and had taken a RA specific medication (methotrexate, leflunomide or biologic) since 2004 (period from which drug reimbursement data was available). Only incident and certain cases were included. Women were excluded if they had an inflammatory bowel disease and/or no information on their smoking status. Passive smoking was assessed by the following question: “When you were children, did you stay in a smoky room?”. Patients were considered exposed if the answer was “yes, a few hours, or yes, several hours a day”. The usual intestinal transit, reported by women prior to RA diagnosis (on average 10 years), were classified as normal transit, chronic diarrhoea, chronic constipation, and alternation between diarrhoea and constipation. The risk of incident RA was estimated using an age-adjusted Cox model that considers smoking status as a time-dependent variable. Results 70598 women from the E3N study were included in the study. A total of 1239 patients reported an incidental RA, of which 350 cases were included in the study (and 280 in the analysis of intestinal transit disorders). Non-ascertained cases were excluded form the analyses. The age at inclusion in the study was 49.0 years (± 6.4). The mean duration of follow-up was 21.2 (± 1.3) years. Passive smoking exposure during childhood increased the association between the RA risk active and adult active smoking. In ever smokers who had childhood passive exposure to smoke, the HR was 1.73 [1.20; 2.50] as compared with non-smokers who were not exposed during childhood, while it was 1.37 [1.08; 1.73] in active smokers who were not exposed during childhood. A history of chronic diarrhea was associated with increased RA risk (HR =2.32 [1.41, 3.81]), while chronic constipation or alternation between diarrhoea and constipation did not. Conclusions This study confirms the link between active smoking and the risk of RA. It suggests for the first time that in smokers, exposure to tobacco early in life, through passive smoking in childhood significantly increases this risk. Our study highlights the importance of avoiding any tobacco environment in children, especially in those with a family history of RA. Also, it shows for the first time an association between a history of chronic diarrhoea and the risk of developing RA. The association supports the hypothesis of dysbiosis (microbiota abnormality) as a risk factor for the emergence of autoimmunity. These data perfectly fit with the preclinical scheme of RA where an external event occurs at an early stage to promote emergence of auto-immunity, followed years after by clinical RA. Disclosure of Interest None declared

Background The role of long -term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn’s disease (CD) is unclear. Aim s For the first time, t o prospectively assess the role of pre -disease alcohol consumption o n the risk of developing UC or CD. Methods Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC - IBD ), incident UC and CD cases and ma tched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non -use, former, light ( ≤ 0.5 and 1 drink/week), below the recommended limits (BRL) ( ≤ 1 and 2 drinks/day), moderate ( ≤ 2.5 and 5 drinks/day) , or heavy use (>2.5 and >5 drinks/ day) for women and men, respectively ; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education , taking light users as the 3 Abstract Background The role of long -term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn’s disease (CD) is unclear. Aim s For the first time, t o prospectively assess the role of pre -disease alcohol consumption o n the risk of developing UC or CD. Methods Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC - IBD ), incident UC and CD cases and ma tched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non -use, former, light ( ≤ 0.5 and 1 drink/week), below the recommended limits (BRL) ( ≤ 1 and 2 drinks/day), moderate ( ≤ 2.5 and 5 drinks/day) , or heavy use (>2.5 and >5 drinks/ day) for women and men, respectively ; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education , taking light users as the reference. Results Out of 262,451 participants in 6 countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/3 2%/2 3%/1 1% UC cases and 7%/2 9%/4 0%/19%/ 5% C D cases were: non -users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non -use, former, light, BRL, moderate and heavy use were : 3%/5%/2 3%/44%/19%/6% and 5%/2%/25%/44%/23 %/1% for UC and CD cases , respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the una djusted and adjusted odds ratios . Conclusion There was no evidence of association s between alcohol use and the odds of developing either UC or CD .

This is a pre-copyedited, author-produced version of an article accepted for publication in Annals of Oncology following peer review. The version of record Chajès, V., Assi, N., Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., ... Romieu, I. (2017). A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study. Annals of Oncology, 28(11), 2836-2842. https://doi.org/10.1093/annonc/mdx482, is available online at: https://doi.org/10.1093/annonc/mdx482. Background: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. Materials and methods: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. Results: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4–Q1) 1.37; 95% confidence interval (CI), 1.14–1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n–7/16:0) [OR (Q4–Q1), 1.28; 95% C, 1.07–1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3–T1)=2.01; 95% CI, 1.03–3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. Conclusion: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. Methods: Pre-diagnostic levels of HbA1c and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA1c levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥6.5%, 48 mmol/mol] vs lowest [≤5.4%, 36 mmol/mol] category), even for individuals with HbA1c levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA1c levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. Conclusions/interpretation: Our data on HbA1c show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA1c levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

Udgivelsesdato: 2010-Nov-2 Background:Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.Methods:We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.Results:After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.Conclusion:Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.British Journal of Cancer advance online publication, 2 November 2010; doi:10.1038/sj.bjc.6605965 www.bjcancer.com.

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.

Introduction Evidence suggests that cutaneous melanoma, the most lethal form of skin cancer, may be influenced by sex hormones. Oral hormones are the leading contraception method in industrialized countries and represent a significant source of exogenous hormone use. Several studies reported a positive association between oral contraceptive (OC) use and melanoma risk. However, findings were conflicting and data from large prospective studies are lacking. Our aim was to explore the associations between OC use and melanoma risk in women. Methods E3 N is a prospective cohort of 98,995 French women aged 40–65 years at inclusion in 1990. Use of oral hormones for contraception was collected through a self-administered questionnaire at baseline, and detailed information on lifetime use of OCs was then recorded every 2–3 years from 1992. We computed hazard ratios (HRs) and 95% Confidence Intervals (CIs) using Cox regression models adjusted for age, birth cohort, pigmentary traits, residential UV exposure in county of birth and at inclusion, and family history of skin cancer. We stratified the results according to melanoma site and histological type using competing-risk models. To examine potential confounding by sun exposure, we used data from E3N-SunExp, a nested case-control study in which a specific questionnaire on lifetime residential and recreational UV exposures was sent to all incident skin cancer cases and 3 controls per case (matched on age, county of birth, education, and length of follow-up in the cohort) in 2008. Analyses in the sub-cohort were performed through logistic regression modelling. Results Between 1992 and 2008, 539 melanoma cases were ascertained among 79,365 women. In age-adjusted models, there was a modest association between ever use of OCs and melanoma risk (HR = 1.18, 95% CI = 0.98–1.42), which was reduced after full adjustment (HR = 1.14, 95% CI = 0.95–1.38). The association was stronger in long-term users (HR = 1.33, 95% CI = 1.00–1.75 for a duration of use of at least 10 years, compared with never use of OCs). Among ever users, there was an inverse association with age at first use (Ptrend = 0.01), consistent with longer durations of OC use in women with a younger age at first use. However, we found no evidence of an association with age at last use or time since last use. When exploring different formulations, the association between ever use of OCs and melanoma risk was restricted to OCs containing high doses of estrogen (≥ 50 μg of ethinyl estradiol) (HR = 1.26, CI = 1.03–1.53). In subtype- and site-specific analyses, ever use of OCs appeared positively associated with all types and sites of melanoma, except the trunk, although no heterogeneity was detected across subtypes (Phomogeneity = 0.54) or sites (Phomogeneity = 0.23). In the E3N-SunExp population, associations between OC use and melanoma risk were not substantially modified after adjustment for residential or recreational UV exposure. However, while we found no association between OC use and sun exposure, we observed that OC use was positively associated with sunscreen use (Ptrend = 0.04 from no protection to increasing SPF) and tanning bed use (odds ratio = 1.14, 95% CI = 1.01–1.29 for ever vs. never use), even after adjusting for age and year of birth. Conclusions Overall, our findings do not support a strong association between OC use and melanoma risk. OC users were more likely to use sunscreen and tanning beds, suggesting a specific profile of OC users regarding their attitude towards tanning. Therefore, we cannot exclude that the observed relation between OC use and melanoma risk, which has been debated in the literature for almost 40 years, could relate to particular sun exposure behaviors in users. Further research, including social and behavioral description of OC users, is thus critical to increase our understanding of the risk profile of women diagnosed with melanoma, and to question the hypothesis of a hormonal influence on melanoma risk.

Background and aims Experimental studies suggest that antioxidants could protect against skin carcinomas. However, epidemiological studies on dietary antioxidant supplement use in relation to risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) yielded inconsistent findings, and very few prospective studies with available sun exposure data have been conducted to date. Our objective was to investigate the relationships between the use of dietary supplements in beta-carotene, and vitamins A, C, and E, and risk of non-melanoma skin cancers (NMSC). Methods E3 N is an ongoing prospective cohort involving 98,995 French women aged 40–65 years at inclusion in 1990. Data on the occurrence of BCC and SCC were collected every 2–3 years through self-administered questionnaires, with skin cancer cases confirmed through pathology reports. Intake of specific antioxidant supplements was collected in 1995. Dietary antioxidant intakes from foods were calculated using data collected via a validated food frequency questionnaire in 1993. We used Cox proportional hazards regression models with age as the time scale to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the risks of BCC and SCC associated with antioxidant supplement use. Models were adjusted for age, birth cohort, pigmentary traits, residential UV exposure at birth and at inclusion, family history of skin cancer, body mass index, physical activity, smoking status, and education. Results Over a mean follow-up of 11.6 years, 1245 BCC and 219 SCC cases were diagnosed among the 63,077 included women. We observed a positive association between vitamin A supplement use and risk of NMSCs (HR = 1.30, 95% CI: 1.02–1.67), particularly BCC (HR = 1.32, 95% CI: 1.01–1.72). There was also a positive association between vitamin E supplement use and NMSC risk (HR = 1.28; 95% CI: 1.05–1.56). Moreover, we found an interaction between vitamin A supplement use and dietary intake of retinol (Pinteraction = 0.04) on the risk of NSMCs: vitamin A supplement use was associated with an increased risk of NMSCs only in women in the highest tertile of dietary retinol intake (HR = 1.89; 95% CI: 1.29–2.75), but not in those in the middle (HR = 1.05, 95% CI: 0.64–1.74) or lowest tertiles of intake (HR = 1.10; 95% CI: 0.70–1.73). However, use of beta-carotene or vitamin C supplements was not associated with NMSC risk. Conclusion Our study suggests an increased risk of NMSCs associated with vitamin A (particularly for BCC) and vitamin E supplement use. The increased risk associated with vitamin A supplement use was restricted to women with high intakes of retinol from foods. These findings suggest that high supplementary intakes of some antioxidants could confer a higher risk of NMSCs in women, particularly in the context of high antioxidant intakes in the diet in the case of retinol. More research is warranted in order to replicate these findings and investigate their underlying mechanisms.

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.

There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P (trend) = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P (trend) = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P (trend) = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (> 12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P (interaction) = .035). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

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.

Introduction et but de l’etude Le beta-carotene semble avoir un effet benefique sur la carcinogenese cutanee au niveau experimental, mais les etudes epidemiologiques disponibles ne confirment pas ces resultats. Les complements solaires, riches en beta-carotene, sont largement utilises en preparation de la peau au soleil. Or, leur effet a long terme sur le risque de cancers cutanes est actuellement inconnu. Notre objectif etait d’explorer les associations entre la consommation de complements solaires et le risque de cancers cutanes dans une etude cas-temoin nichee dans E3N. Materiel et methodes E3N (etude epidemiologique aupres de femmes de l’education nationale) est une etude de cohorte prospective incluant 98 995 femmes francaises âgees de 40 a 65 ans en 1990. Des donnees sur le phenotype pigmentaire ont ete recueillies a l’inclusion. En 2008, un questionnaire specifique sur l’exposition solaire a ete envoye a tous les cas declares de cancers de la peau ainsi qu’a 3 temoins par cas, apparies aux cas sur l’âge, le departement de naissance et le niveau d’etudes. L’etude a inclus 366 cas de melanome, 1027 cas de carcinome basocellulaire (CBC), 165 cas de carcinome spinocellulaire (CSC) et 3647 temoins. Le questionnaire a recolte des donnees sur l’utilisation et la frequence de consommation de complements solaires avant, pendant ou apres une periode d’exposition solaire au cours des 10 annees precedentes, ainsi que sur les comportements d’exposition solaire au cours de la vie. Les analyses ont ete realisees a l’aide de modeles de regression logistique. Resultats et analyse statistique Les femmes utilisant regulierement des complements solaires etaient significativement plus a risque de CBC que les non-utilisatrices (parfois : odds-Ratio [OR] = 1,24 (intervalle de confiance a 95 % [IC] = 0,97–1,59) ; souvent/toujours : OR = 1,57 (1,09–2,24), compare a jamais, ptend = 0,004), mais pas de melanome ou de CSC. L’ajustement sur les facteurs pigmentaires ou sur differents facteurs d’exposition solaire avait generalement peu d’effet sur les resultats ; cependant, l’association avec le CBC etait significativement reduite apres ajustement simultane de ces facteurs. L’association entre la consommation de complements solaires et le risque de CBC differait selon le nombre total d’heures d’exposition solaire au cours de la vie (pinteraction = 0,05) et la couleur des yeux (pinteraction = 0,03) : l’augmentation de risque etait restreinte au tercile superieur du nombre d’heures d’exposition (parfois : OR = 1,26 ; souvent/toujours : OR = 2,49 ; ptend = 0,04) et aux femmes ayant les yeux bleus/gris (souvent/toujours : OR = 18,62 ; ptend = 0,004). Conclusion Notre etude est la premiere a examiner les relations entre la consommation de complements solaires et le risque de cancers cutanes et suggere une augmentation du risque de CBC associee a la prise de ces complements. Etant donne l’impact potentiel de ces resultats pour la sante publique, davantage de recherches seront necessaires afin de confirmer cette relation et d’examiner ses facteurs mediateurs potentiels.

Introduction et but de l’etude Un exces de stress oxydant est un facteur de risque majeur de maladies comme l’hypertension, le diabete, et les cancers (1–4). L’alimentation, et en particulier les produits vegetaux, sont riches en micronutriments ayant des proprietes antioxydantes comme les polyphenols et certaines vitamines (5). Ces molecules pourraient agir en synergie pour diminuer le stress oxydant dans les cellules (6–8). Nous nous sommes interesses a la relation entre capacite antioxydante totale non-enzymatique de l’alimentation et risque de deces toutes causes et cause-specifique des femmes de la cohorte E3N. Materiel et methodes La cohorte E3N, initiee en 1990, inclut 98 995 femmes nees entre 1925 et 1950, assurees par la MGEN (Mutuelle Generale de l’Education Nationale) (9). La population d’etude etait constituee de 72 510 femmes suivies entre 1993 et 2008 et ayant rempli un questionnaire alimentaire qualitatif et quantitatif (10). La capacite antioxydante totale de l’alimentation a ete estimee avec deux methodes complementaires : le FRAP (Ferric Reducing Antioxidant Power), et le TRAP (Total radical-trapping antioxidant parameter method) (11 ;12). Le risque de deces a ete etudie par un modele de Cox avec l’âge en echelle de temps, ajuste pour les facteurs de confusion potentiels. Resultats et Analyse statistique Pendant les 13,6 annees de suivi, 2 878 deces sont survenus dont 1 776 cas par cancer et 305 cas par maladie cardiovasculaire. Lors des analyses multivariees, la capacite antioxydante totale de l’alimentation etait inversement associee a la mortalite totale (Hazard ratio pour le dernier versus premier quartile : FRAP : HR4 = 0,84, IC 95 % 0,74–0,95, ptendance = 0,02 ; TRAP : HR4 = 0,85, IC 95 % 0,77–0,96, ptendance = 0,02). Il existait une association inverse entre la capacite antioxydante totale de l’alimentation et la mortalite par maladie cardiovasculaire (FRAP : HR4 = 0,58, IC 95 % 0,38–0,87, ptendance = 0,006 ; TRAP : HR4 = 0,51, IC 95 % 0,34–0,77, ptendance = 0,001), mais pas avec la mortalite par cancer (Hazard ratio pour le dernier versus premier quartile : FRAP : HR4 =0,91, IC 95 % 0,78–1,08, ptendance = 0,44 ; TRAP : HR4 = 0,92, IC 95 % 0,79–1,08, ptendance = 0,54). Conclusion Ce travail a permis de mettre en evidence une diminution significative de la mortalite, en particulier par maladies cardiovasculaires, associee a la consommation totale d’antioxydants dans les aliments mesuree par deux methodes complementaires, chez les femmes de la cohorte E3N. Ces resultats sont en accord avec les conseils de prevention axes sur une consommation renforcee de fruits et legumes.