Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

OBJECTIVE: 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. DESIGN: 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. METHODS: 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 VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 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. RESULTS: 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). CONCLUSIONS: 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.

Association between cardiovascular risk-factors and venous thromboembolism in a large longitudinal study of French women.

BACKGROUND: Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI. METHODS: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism. RESULTS: During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI. CONCLUSIONS: Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.

Associations between smoking and blood-group, and the risk of dyslipidaemia amongst French women.

Dyslipidaemia is a major risk factor for cardio-vascular disease, as it promotes atherosclerosis. While cross-sectional studies have identified higher serum cholesterol amongst individuals with the A blood group, there is less evidence from prospective studies whether this translates into a higher risk of dyslipidaemia that requires treatment, nor if this genetic factor interacts with smoking status. This study aimed to prospectively determine potential associations between smoking, ABO blood groups, and risk of incident dyslipidaemia requiring treatment, and to assess associations over strata of blood ABO group. We assessed associations between blood ABO group, smoking and dyslipidaemia in 74,206 women participating in the E3N cohort. We included women who did not have cardiovascular disease at baseline. Logistic regression was used to determine associations between ABO group, smoking and prevalent dyslipidaemia at baseline. Cox proportional hazard models were then used to determine if blood ABO group and smoking were associated with the risk of incident dyslipidaemia, amongst women free of dyslipidaemia at baseline. At baseline 28,281 women with prevalent dyslipidaemia were identified. Compared to the O-blood group, the non-O blood group was associated higher odds of with prevalent dyslipidaemia (ORnon-O = 1.09 [1.06: 1.13]). Amongst the women free of dyslipidaemia at baseline, 6041 incident cases of treated dyslipidaemia were identified during 454,951 person-years of follow-up. The non-O blood groups were associated with an increased risk of dyslipidaemia when compared to the O-group (HRnon-O = 1.16 [1.11: 1.22]), specifically the A blood-group (HRA = 1.18 [1.12: 1.25]). Current smokers were associated with an increased risk of incident dyslipidaemia (HR smokers = 1.27 [1.16: 1.37]), compared to never-smokers. No evidence for effect modification between smoking and ABO blood group was observed (p-effect modification = 0.45), although the highest risk was observed among AB blood group women who smoked (HR = 1.76 [1.22: 2.55]). In conclusion, the non-O blood groups, specifically the A group were associated with an increased risk of dyslipidaemia. Current smokers were associated with a 30% increased risk of dyslipidaemia. These results could aid in personalised approaches to the prevention of cardiovascular risk-factors.

Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study.

BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. METHODS: We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status. RESULTS: Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC. CONCLUSIONS: Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.

Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort.

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).

Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

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 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years 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 11 years 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 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (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 5 years of follow-up.

Decline in Instrumental Activities of Daily Living over 4-Year: The Association with Hearing, Visual and Dual Sensory Impairments among Non-Institutionalized Women.

OBJECTIVE: Most older adults express the wish to live at home as long as possible, thus autonomy promoting measures are essential. Hearing and visual impairments are common among older people, and they have been consistently associated with functional disability. However, longitudinal data are scarce, notably regarding dual sensory impairments (both in hearing and vision). We aimed at assessing the relationship between hearing, visual, and dual sensory impairments, and subsequent decline in instrumental activities of daily living (IADL). DESIGN: Longitudinal. SETTING: the French E3N-elderly sub-cohort. PARTICIPANTS: 4,010 community-dwelling older women born between 1925 and 1930, and free of IADL limitations in 2006. MEASUREMENTS: Hearing and visual impairments were self-reported in 2006. IADLs were evaluated in 2006 and 2010. RESULTS: After 4 years of follow-up, 588 women became limited in their IADLs. In logistic regression models adjusted for potential confounders, odds ratios [95% confidence interval] for developing IADL limitations were 1.18 [0.98; 1.41], 1.98 [1.26; 3.11], and 2.61 [1.50; 4.54] for hearing, visual, or both sensory impairments respectively, compared with no sensory impairment at baseline. CONCLUSION: Results suggest that among autonomous older women, visual, and to a lesser extent, hearing impairment, have a short-term negative impact on their ability to perform daily activities, with some evidence of a multiplicative effect between sensory impairments. Appropriate evaluation and management of sensory impaired elderly, and more particularly those with dual impairments, may contribute to prevent disability in aging.

Postmenopausal hormone use and cutaneous melanoma risk: A French prospective cohort study.

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.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

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 from375 incident pancreatic cancer cases and375 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.

Oral contraceptive use and cutaneous melanoma risk: a French prospective cohort study.

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.

Determinants of 20-year non-progression to Type 2 diabetes in women at very high risk: the E3N cohort study.

AIMS: To identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk. METHODS: Between 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. RESULTS: During 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. CONCLUSIONS: We 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.

A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

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.

Associations among body size across the life course, adult height and endometriosis.

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 Epidémiologique auprès 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 (<158 cm) (162-164 cm: OR = 1.28, 95% CI = 1.12-1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18-1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05-1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis. LIMITATIONS REASONS FOR CAUTION: Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further. STUDY FUNDING/COMPETING INTEREST(S): The Mutuelle Générale de l'Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011-302078). The authors have no conflicts of interest to declare.

Alcohol consumption and the risk of renal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). Wozniak MB, Brennan P, Brenner DR, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Fagherazzi G, Katzke V, Kühn T, Boeing H, Bergmann MM, Steffen A, Naska A, Trichopoulou A, Trichopoulos D, Saieva C, Grioni S, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Hjartåker A, Weiderpass E, Arriola L, Molina-Montes E, Duell EJ, Santiuste C, Alonso de la Torre R, Barricarte Gurrea A, Stocks T, Johansson M, Ljungberg B, Wareham N, Khaw KT, Travis RC, Cross AJ, Murphy N, Riboli E, Scelo G.Int J Cancer. 2015 Oct 15;137(8):1953-66. [Epub 2015 Apr 28]. doi: 10.1002/ijc.29559.

Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment vs. the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), and 0.91 (0.63-1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.

No association of alcohol use and the risk of ulcerative colitis or Crohn's disease: data from a European Prospective cohort study (EPIC).

BACKGROUND/OBJECTIVES: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. SUBJECTS/METHODS: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched 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 per week), below the recommended limits (BRL) (⩽1 and 2 drinks per day), moderate (⩽2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per 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 six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD 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%/23%/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 unadjusted and adjusted odds ratios. CONCLUSION: There was no evidence of associations between alcohol use and the odds of developing either UC or CD.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

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 vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty-seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Functional gastrointestinal disorders and incidence of type 2 diabetes: Evidence from the E3N-EPIC cohort study.

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.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.

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.