Egg and cholesterol intake and incident type 2 diabetes among French women.

Egg consumption is a major source of dietary cholesterol, a nutrient that may disrupt glucose metabolism. We prospectively evaluated the relation between egg consumption and cholesterol-intake and diabetes in 65 364 French disease-free women who responded to a validated diet history questionnaire in 1993. Egg consumption included hardboiled eggs and eggs consumed in an omelette or a mixed dish, and dietary cholesterol was estimated using a French nutrient database. Over 14 years of follow-up, 1803 incident diabetes cases were identified through self-reports, supplementary questionnaires and drug reimbursement information. Multivariable Cox regression models were adjusted for age, education, menopause, menopausal hormone therapy, hypertension and hypercholesterolaemia, BMI, physical activity, smoking, alcohol, fruit, vegetables, processed red meat, coffee and sugar and artificially sweetened beverages. No association was observed between egg consumption and risk of type 2 diabetes. When comparing women who consumed at least five eggs per week with non-consumers, the multivariable hazard ratio (HR) was found to be 1·00 (95 % CI 0·78, 1·29; across categories, P trend=0·11). Women in the highest quintile of dietary cholesterol had a 40 % higher rate of diabetes compared with those in the lowest quintile (HR 1·40; 95 % CI 1·19, 1·63; across quintiles, P trend<0·0001). A 100 mg increase of dietary cholesterol per 4184 kJ (or 1000 kcal) was associated with a 14 % increase in the risk of diabetes (HR 1·14; 95 % CI 1·02, 1·26). In this large prospective cohort, we observed an association between dietary cholesterol and type 2 diabetes, but no association with egg consumption. In the absence of a clear underlying mechanism and potential residual confounding, these results should be interpreted with caution.

Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: results from the EPIC-EURGAST study.

MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value = 1.7 × 10(-4) ; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value = 5.38 × 10(-3) ; OR = 0.56, 95% CI = 0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value = 5.40 × 10(-3) ; OR = 1.41, 95% CI = 1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.

Childhood and adult secondhand smoke and type 2 diabetes in women.

OBJECTIVE: The objective of this study was to evaluate the relationship between childhood and adult secondhand smoke and type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study among 37,343 French women from the E3N-EPIC (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition) who never smoked and who were free of type 2 diabetes, cancer, or cardiovascular disease at baseline in 1992. Self-reported childhood secondhand smoke exposure was defined as having at least one parent who smoked. Adult secondhand smoke was defined as the sum of self-reported hours recorded at baseline of exposure to tobacco smoke from a spouse who smoked (or domestic close contact) and from outside the home. RESULTS: Between 1992 and 2007, 795 cases of incident type 2 diabetes were identified and validated through a drug reimbursement dataset and a specific questionnaire. Women with at least one parent who smoked appeared to have an 18% higher rate of type 2 diabetes than women with parents who did not smoke (age-adjusted hazard ratio 1.18 [95% CI 1.02-1.36]). Adult secondhand smoke exposure (no exposure versus ≥ 4 h/day) was associated with an increased rate of type 2 diabetes (1.36 [1.05-1.77], P = 0.002 for trend) after adjusting for parental history of diabetes, education, body silhouette at age 8, childhood secondhand smoke exposure, physical activity, body mass index, hypertension, hypercholesterolemia, menopausal status and hormone use, alcohol intake, and processed red meat and coffee consumption. CONCLUSIONS: This prospective analysis suggests that secondhand smoke exposure in childhood and adulthood are associated with a higher rate of type 2 diabetes.

Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort.

BACKGROUND: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index. RESULTS: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001). CONCLUSIONS: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels. IMPACT: This study strengthens the evidence for the benefits of a smoking ban in public places.

Differential effects of coffee on the risk of type 2 diabetes according to meal consumption in a French cohort of women: the E3N/EPIC cohort study.

BACKGROUND: Coffee consumption has been associated with a lower risk of diabetes, but little is known about the mechanisms responsible for this association, especially related to the time when coffee is consumed. OBJECTIVE: We examined the long-term effect of coffee, globally and according to the accompanying meal, and of tea, chicory, and caffeine on type 2 diabetes risk. DESIGN: This was a prospective cohort study including 69,532 French women, aged 41-72 y from the E3N/EPIC (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale/European Prospective Investigation into Cancer and Nutrition) cohort study, without diabetes at baseline. Food and drink intakes per meal were assessed by using a validated diet-history questionnaire in 1993-1995. RESULTS: During a mean follow-up of 11 y, 1415 new cases of diabetes were identified. In multivariable Cox regression models, the hazard ratio in the highest category of coffee consumption [> or =3 cups (375 mL)/d] was 0.73 (95% CI: 0.61, 0.87; P for trend < 0.001), in comparison with no coffee consumption. This inverse association was restricted to coffee consumed at lunchtime (hazard ratio: 0.66; 95% CI: 0.57, 0.76) when comparing >1.1 cup (125 mL)/meal with no intake. At lunchtime, this inverse association was observed for both regular and decaffeinated coffee and for filtered and black coffee, with no effect of sweetening. Total caffeine intake was also associated with a statistically significantly lower risk of diabetes. Neither tea nor chicory consumption was associated with diabetes risk. CONCLUSIONS: Our data support an inverse association between coffee consumption and diabetes and suggest that the time of drinking coffee plays a distinct role in glucose metabolism.