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There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n=1095) and borderline (n=96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR=1.22, 95% CI=1.02-1.48, Ptrend=0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.

Background and aims Several epidemiological studies highlighted the association between folate and B-vitamins low intake and cardiovascular diseases (CVD) risk. Contrasting results were reported on the relationship between folate intake and DNA-methylation. Folate and B-vitamins may modulate DNA-methylation of specific enzymes which are included in the One-Carbon Metabolism (OCM) and in the homocysteine (Hcy) pathways. The aim of the study was to evaluate whether DNA-methylation profiles of OCM and Hcy genes could modulate the myocardial infarction (MI) risk conferred by a low B-vitamins intake. Methods and results Study sample (206 MI cases and 206 matched controls) is a case-control study nested in the prospective EPIC cohort. Methylation levels of 33 candidate genes where extracted by the whole epigenome analysis (Illumina-HumanMethylation450K-BeadChip). We identified three differentially methylated regions in males (TCN2 promoter, CBS 5′UTR, AMT gene-body) and two in females (PON1 gene-body, CBS 5′UTR), each of them characterized by an increased methylation in cases. Functional in silico analysis suggested a decreased expression in cases. A Recursively Partitioned Mixture Model cluster algorithm identified distinct methylation profiles associated to different MI risk: high-risk vs. low-risk methylation profile groups, OR = 3.49, p = 1.87 × 10 − 4 and OR = 3.94, p = 0.0317 in males and females respectively (multivariate logistic regression adjusted for classical CVD risk factors). Moreover, a general inverse relationship between B-vitamins intake and DNA-methylation of the candidate genes was observed. Conclusions Our findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake.

BACKGROUND: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS: We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS: The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13). INTERPRETATION: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING: European Community's Seventh Framework Program (FP7/2007-2011).

BACKGROUND: The glycemic potential of a diet is associated with chronically elevated insulin concentrations, which may augment breast cancer (BC) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis. It is unclear whether this effect differs by BC phenotype. OBJECTIVE: The objective was to investigate the relation between glycemic index (GI), glycemic load (GL), and total carbohydrate intake with BC by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34-66 y (5th to 95th percentiles) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary questionnaires. We used multivariable Cox proportional hazards models to quantify the association between GI, GL, and carbohydrate intake and BC risk. BC tumors were classified by receptor status. RESULTS: Overall GI, GL, and carbohydrates were not related to BC. Among postmenopausal women, GL and carbohydate intake were significantly associated with an increased risk of estrogen receptor-negative (ER(-)) BC when extreme quintiles (Q) were compared [multivariable HR(Q5-Q1) (95% CI) = 1.36 (1.02, 1.82; P-trend = 0.010) and HR(Q5-Q1) = 1.41 (1.05, 1.89; P-trend = 0.009), respectively]. Further stratification by progesterone receptor (PR) status showed slightly stronger associations with ER(-)/PR(-) BC [HR(Q5-Q1) (95% CI) = 1.48 (1.07, 2.05; P-trend = 0.010) for GL and HR(Q5-Q1) = 1.62 (1.15, 2.30; P-trend = 0.005) for carbohydrates]. No significant association with ER-positive BC was observed. CONCLUSION: Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(-) and ER(-)/PR(-) BC among postmenopausal women.

Background: Many observational studies support the recommendation to eat sufficient amounts of fruit and vegetables as part of a healthy diet. Objective: The present study aimed to investigate the association between consumption of fruit, vegetables, and olive oil and the incidence of coronary heart disease (CHD) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts in northern (Turin and Varese), central (Florence), and southern (Naples and Ragusa) Italy. Design: Baseline dietary, anthropometric, and lifestyle characteristics were collected. Major events of CHD (fatal and nonfatal myocardial infarction and coronary revascularization) were identified through a review of clinical records. Analyses were stratified by center and adjusted for hypertension, smoking, education, menopause, physical activity, anthropometric measures, nonalcohol energy, alcohol, total meat, vegetables in analyses for fruit, and fruit in analyses for vegetables. Results: During a mean follow-up of 7.85 y, 144 major CHD events were identified. A strong reduction in CHD risk among women in the highest quartile of consumption of leafy vegetables (hazard ratio: 0.54; 95% CI: 0.33, 0.90; P for trend = 0.03) and olive oil (hazard ratio: 0.56; 95% CI: 0.31, 0.99; P for trend = 0.04) was found. In contrast, no association emerged between fruit consumption and CHD risk. Conclusion: An inverse association between increasing consumption of leafy vegetables and olive oil and CHD risk emerged in this large cohort of Italian women. Am J Clin Nutr doi: 10. 3945/ajcn.110.000521.

A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk. © 2010 Elsevier Ltd. All rights reserved.

Introduction Epidemiological studies have shown that dietary behaviour is an important aetiological factor in various chronic diseases. We used principal component factor analysis to identify dietary patterns and to examine the associations of these patterns with health-related variables in a sample of elderly (≥60 years) Italians participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods and results Exploratory factor analysis was applied to the intake of food groups as estimated by semi-quantitative food questionnaires. Individual participants were assigned factor scores, indicating the extent to which their diet conformed to each of the four dietary patterns identified: prudent (cooked vegetables, pulses, cabbage, seed oil and fish); pasta & meat (pasta, tomato sauce, red meat, processed meat, bread and wine); olive oil & salad (raw vegetables, olive oil, soup and chicken); and sweet & dairy (sugar, cakes, ice cream, coffee and dairy). Highly educated people had high scores on prudent and low scores on pasta & meat . The pasta & meat and prudent patterns were strongly positively associated with body mass index (BMI) and waist-to-hip ratio (WHR) in men and women. Hyperlipidaemic men and women consumed more of the prudent and olive oil & salad patterns and less of the sweet & dairy pattern than those with normal lipids. The olive oil & salad was significantly higher and the pasta & meat and sweet & dairy patterns significantly lower in men and women who had dieted over the previous year, suggesting awareness of the health consequences of these patterns. Conclusions Dietary pattern analysis provides a characterization of recurrent dietary behaviour in elderly people, and can be used to provide tangible dietary advice to elderly people.

The diagnosis of parathyroid carcinoma (PC) is difficult and based on morphological features that are not totally reliable. Several molecular markers proved useful in the evaluation of PC, but their sensitivity, specificity, or both are rather low. With the aim of identifying a marker of malignancy in parathyroid tumors, we tested the expression of galectin-3 (Gal-3), a lectin expressed in several malignant tumors, including follicular carcinomas (but not adenomas) of the thyroid. Twenty-six PCs and 30 control parathyroid adenomas (PAs) were collected. The PCs had been diagnosed based on capsular/vascular invasion (26/26 cases), extraparathyroid infiltration (16), local recurrence (9), and distant metastases (6). All cases were immunohistochemically tested for Gal-3 and for other markers claimed to be useful in the differential diagnosis of parathyroid neoplasms, namely, Ki67, p27, and bcl2. Gal-3 was expressed by 24 of the PC (92.3%), but only 1 PA (3.3%) (P.001). All metastasizing PCs were Gal-3-positive. As expected, the Ki67 proliferative index was higher in PCs (mean, 6.7%) than in PAs (1.9%); p27 was down-regulated in 61.5% of PCs and only 33.3% of PAs, whereas bcl2 was strongly positive in most PAs and in 38.5% of PCs. In a suspected PC, the association of Gal-3 with Ki67 (using a cutoff of 6% for the proliferative activity) appeared the best marker combination (sensitivity 96.2%, specificity 90%), and the profile Gal-3-positive/Ki676% was unique to PCs. We conclude that Gal-3 immunostaining is a valuable tool to support a diagnosis of PC in highly proliferating (Ki676%) tumors affecting a single parathyroid gland.