Endometrial cancer is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30-65 years) including 855 incident endometrial cancer cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict endometrial cancer (EC) was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation.Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri-and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71% for a model based on age alone to 77% (overall C statistic), and the model was wellcalibrated (ratio of expected to observed cases = 0.99).Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation. Husing_EndometrCaRiskmodel_EurJEpidemiol_2015_authorversion4

The role of endogenous androgens and sex hormone‐binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64–0.97]). Moreover, associations differed for low‐grade and high‐grade carcinomas, with positive associations for low‐grade and inverse associations for high‐grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98–4.06]; high grade: ORlog2 = 0.75 [0.61–0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.

Background: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n ¼ 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.

Background:Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.Methods:Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.Results:No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).Conclusions:Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

Several studies have examined environmental factors and inflammatory bowel diseases (IBD) using traditional approaches; however, provided results are still conflicting. Our aim was to determine whether lifestyle and nutrient exposures, related to IBD in observational meta-analyses, influence IBD risk using a Mendelian randomization (MR) approach. A two-sample MR approach was applied on summary-level genome-wide association results. Genetic variants strongly associated with measures of tobacco smoking, obesity and fat distribution, physical activity, and blood levels of vitamins and fatty acids were evaluated on genetic data from international IBD consortia including a total of 25,042 IBD cases (12,194 cases of Crohn’s disease (CD) and 12,366 cases of ulcerative colitis (UC)) and 34,915 controls. Our results indicated that, among lifestyle exposures, being a smoker was positively associated with CD (OR 1.13, P = 0.02), but it was not associated with UC risk (OR 0.99, P = 0.88). Body-mass index (BMI) and body fat percentage were positively associated with CD (OR 1.11, P = 0.02, per standard deviation (SD) of 4.6 kg/m2; and OR 1.50, P = 3 × 10–10, per SD of 6.6%; respectively); while for UC, BMI was inversely associated (OR 0.85, P = 5 × 10–5; per SD) and body fat percentage showed a OR of 1.11 (P = 0.11; per SD). Additionally, among nutrient exposures, omega-3 fatty acids levels were inversely associated with CD (OR 0.67, P = 2 × 10–6). Our MR results did not support a protective effect for being a smoker on UC risk; however, they are compatible with a risk effect for higher body fat proportion and a protective role for higher levels of omega-3 fatty acids on CD etiology.