Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.

Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

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.

Dietary glycemic index, glycemic load, and cancer risk: results from the EPIC-Italy study.

Factors linked to glucose metabolism are involved in the etiology of several cancers. High glycemic index (GI) or high glycemic load (GL) diets, which chronically raise postprandial blood glucose, may increase cancer risk by affecting insulin-like growth factor. We prospectively investigated cancer risk and dietary GI/GL in the EPIC-Italy cohort. After a median 14.9 years, 5112 incident cancers and 2460 deaths were identified among 45,148 recruited adults. High GI was associated with increased risk of colon and bladder cancer. High GL was associated with: increased risk of colon cancer; increased risk of diabetes-related cancers; and decreased risk of rectal cancer. High intake of carbohydrate from high GI foods was significantly associated with increased risk of colon and diabetes-related cancers, but decreased risk of stomach cancer; whereas high intake of carbohydrates from low GI foods was associated with reduced colon cancer risk. In a Mediterranean population with high and varied carbohydrate intake, carbohydrates that strongly raise postprandial blood glucose may increase colon and bladder cancer risk, while the quantity of carbohydrate consumed may be involved in diabetes-related cancers. Further studies are needed to confirm the opposing effects of high dietary GL on risks of colon and rectal cancers.

Dietary glycemic index, glycemic load and cancer: An overview of the literature.

AIMS: The aim of this paper is to provide an overview of the current evidence for associations between dietary glycemic index (GI) and dietary glycemic load (GL), and the risk of various types of cancer, and to summarize mechanisms proposed to explain the associations found. DATA SYNTHESIS: Medline was searched for cohort studies, case-control studies, and meta-analyses, published up to February 2016, that examined associations between dietary GI/GL and cancer. Findings from the main meta-analyses showed a weak-to-moderate association of high dietary GI/GL with increased risk of some cancers. High dietary GI but not GL was significantly and consistently associated with increased colorectal cancer risk in both cohort and case-control studies. Dietary GL was directly associated with breast and endometrial cancer risk in cohort studies. Positive associations between dietary GI or GL and cancer risk were found more frequently in case-control studies than cohort studies. The main mechanism for these associations is thought to be chronic hyperinsulinemia. Insulin is itself a mitogen and also increases the bioactivity of insulin-like growth factors which can promote cancer by inhibiting apoptosis and stimulating cell proliferation. CONCLUSIONS: The review has uncovered consistent evidence that high dietary GI is associated with increased risk of colorectal cancer, and that high dietary GL is associated with increased risk of breast and endometrial cancer. However the risk increases are small or moderate.

Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes - The TOSCA.IT study.

BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.

Flavonoid and lignan intake in a Mediterranean population: proposal for a holistic approach in polyphenol dietary analysis, the Moli-sani Study.

BACKGROUND/OBJECTIVES: The objective of this study is to extract and assess data on the dietary intake of flavonoids and lignans in a healthy free-living Mediterranean population, using newly updated harmonized European Union food composition data. This work also aimed at analyzing in a holistic way the total content of the diet in major classes of polyphenols. SUBJECTS/METHODS: Six thousand nine hundred and eighty-one men and 7048 women (aged ⩾ 35 years) of the Moli-sani cohort, randomly recruited from the general population, were analyzed. The European Prospective Investigation into Cancer (EPIC) and Nutrition-Food Frequency Questionnaire was used for dietary assessment. The polyphenol content of each food group was evaluated using Eurofir BioActive Substances in Food Information System and the United States Department of Agriculture food composition tables (FCTs), when data were missing. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated and polyphenol antioxidant content (PAC) score (-28, 28) constructed, to assess the total content of the diet in these nutrients. RESULTS: Seasonal and citrus fruits, leafy, grain, pod and root vegetables, and onions and garlic accounted for different proportions (11-70%) of the total intake of different polyphenols. Within the Moli-sani population, men or older, or no/former smokers, or physically active or obese/overweight individuals presented higher consumption of flavonoids, lignans and PAC score (P for all <0.01). Multiple regression analysis showed that PAC score and its seven components were positively associated with Mediterranean diet (MeD) adherence in both genders (ß-coefficient >0, P<0.001). In addition, 1 unit increase in PAC score was associated with 7.1-7.8% increase in the likelihood of high MeD adherence (P<0.001). CONCLUSIONS: The intake of flavonoids and lignans in an European Union population was calculated using harmonized European Union FCT data. In addition, a holistic approach in dietary analysis of polyphenol intake was proposed.

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

Dietary glycemic index and glycemic load and risk of colorectal cancer: results from the EPIC-Italy study.

A carbohydrate-rich diet, resulting in high blood glucose and insulin, has been hypothesized as involved in colorectal cancer etiology. We investigated dietary glycemic index (GI) and glycemic load (GL), in relation to colorectal cancer, in the prospectively recruited EPIC-Italy cohort. After a median 11.7 years, 421 colorectal cancers were diagnosed among 47,749 recruited adults. GI and GL were estimated from validated food frequency questionnaires. Multivariable Cox modeling estimated hazard ratios (HRs) for associations between colorectal cancer and intakes of total, high GI and low GI carbohydrate and GI and GL. The adjusted HR of colorectal cancer for highest versus lowest GI quartile was 1.35; 95% confidence interval (CI) 1.03-1.78; p trend 0.031. Increasing high GI carbohydrate intake was also significantly associated with increasing colorectal cancer risk (HR 1.45; 95% CI 1.04-2.03; p trend 0.034), whereas increasing low GI carbohydrate was associated with reducing risk (HR 0.73; 95% CI 0.54-0.98; p trend 0.033). High dietary GI and high GI carbohydrate were associated with increased risks of cancer at all colon sites (HR 1.37; 95% CI 1.00-1.88, HR 1.80; 95% CI 1.22-2.65, respectively), whereas high GI carbohydrate and high GL were associated with increased risk of proximal colon cancer (HR 1.94; 95% CI 1.18-3.16, HR 2.01; 95% CI 1.08-3.74, respectively). After stratification for waist-to-hip ratio (WHR), cancer was significantly associated with GI, and high GI carbohydrate, in those with high WHR. These findings suggest that high dietary GI and high carbohydrate intake from high GI foods are associated with increased risk of colorectal cancer.

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort.

BACKGROUND: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations. RESULTS: We observed no association between IGF-I and EOC overall or by tumour characteristics. CONCLUSIONS: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

Functional foods and cardiometabolic diseases* International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

Usual energy and macronutrient intakes in 2-9-year-old European children.

OBJECTIVE: Valid estimates of population intakes are essential for monitoring trends as well as for nutritional interventions, but such data are rare in young children. In particular, the problem of misreporting in dietary data is usually not accounted for. Therefore, this study aims to provide accurate estimates of intake distributions in European children. DESIGN: Cross-sectional setting-based multi-centre study. SUBJECTS: A total of 9560 children aged 2-9 years from eight European countries with at least one 24-h dietary recall (24-HDR). METHODS: The 24-HDRs were classified in three reporting groups based on age- and sex-specific Goldberg cutoffs (underreports, plausible reports, overreports). Only plausible reports were considered in the final analysis (N=8611 children). The National Cancer Institute (NCI)-Method was applied to estimate population distributions of usual intakes correcting for the variance inflation in short-term dietary data. RESULTS: The prevalence of underreporting (9.5%) was higher compared with overreporting (3.4%). Exclusion of misreports resulted in a shift of the energy and absolute macronutrient intake distributions to the right, and further led to the exclusion of extreme values, that is, mean values and lower percentiles increased, whereas upper percentiles decreased. The distributions of relative macronutrient intakes (% energy intake from fat/carbohydrates/proteins) remained almost unchanged when excluding misreports. Application of the NCI-Method resulted in markedly narrower intake distributions compared with estimates based on single 24-HDRs. Mean percentages of usual energy intake from fat, carbohydrates and proteins were 32.2, 52.1 and 15.7%, respectively, suggesting the majority of European children are complying with common macronutrient intake recommendations. In contrast, total water intake (mean: 1216.7 ml per day) lay below the recommended value for >90% of the children. CONCLUSION: This study provides recent estimates of intake distributions of European children correcting for misreporting as well as for the daily variation in dietary data. These data may help to assess the adequacy of young children's diets in Europe.

Adherence to a Mediterranean-like dietary pattern in children from eight European countries. The IDEFICS study.

BACKGROUND: Despite documented benefits of a Mediterranean-like dietary pattern, there is a lack of knowledge about how children from different European countries compare with each other in relation to the adherence to this pattern. In response to this need, we calculated the Mediterranean diet score (MDS) in 2-9-year-old children from the Identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) eight-country study. SUBJECTS AND METHODS: Using 24 h dietary recall data obtained during the IDEFICS study (n=7940), an MDS score was calculated based on the age- and sex-specific population median intakes of six food groups (vegetables and legumes, fruit and nuts, cereal grains and potatoes, meat products and dairy products) and the ratio of unsaturated to saturated fats. For fish and seafood, which was consumed by 10% of the population, one point was given to consumers. The percentages of children with high MDS levels (>3) were calculated and stratified by sex, age and by having at least one migrant parent or both native parents. Demographic (sex and age) and socioeconomic characteristics (parental education and income) of children showing high (>3) vs low (⩽3) MDS levels were examined. RESULTS: The highest prevalence of children with MDS>3 was found among the Italian pre-school boys (55.9%) and the lowest among the Spanish school-aged girls (26.0%). Higher adherence to a Mediterranean-like dietary pattern was not associated with living in a Mediterranean country or in a highly educated or high-income family, although with some exceptions. Differences in adherence between boys and girls or age groups varied between countries without any general pattern. CONCLUSIONS: With the exception of Italian pre-schoolers, similar adherence levels to a Mediterranean-like dietary pattern have been observed among European children.

Dietary patterns and fatty acids levels of three European populations. Results from the IMMIDIET study.

BACKGROUND AND AIMS: Differences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels. METHODS: In the framework of the IMMIDIET Project, 1604 subjects (802 male-female pairs) aged 26-65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual. RESULTS: Italian cohort showed lower plasma and RBC n-3 levels than participants of the other two populations (P<0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n-3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n-3 variation as compared to vegetable oils and polyphenol-rich foods. CONCLUSION: The Italian cohort presented significant lower plasma and RBC n-3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n-3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels.

Country-specific dietary patterns and associations with socioeconomic status in European children: the IDEFICS study.

BACKGROUND/OBJECTIVES: Children from lower socioeconomic status (SES) may be at higher risk of unhealthy eating. We described country-specific dietary patterns among children aged 2-9 years from eight European countries participating in the IDEFICS study and assessed the association of dietary patterns with an additive SES indicator. SUBJECTS/METHODS: Children aged 2-9 years from eight European countries were recruited in 2007-2008. Principal component analysis was applied to identify dietary country-specific patterns. Linear regression analyses were applied to assess their association with SES. RESULTS: Two to four dietary patterns were identified in the participating regions. The existence of a 'processed' pattern was found in the eight regions. Also, a 'healthy' pattern was identified in seven of the eight regions. In addition, region-specific patterns were identified, reflecting the existing gastronomic and cultural differences in Europe. The 'processed' pattern was significantly inversely associated with the SES additive indicator in all countries except Sweden, whereas the 'healthy' pattern was positively associated with SES in the Belgian, Estonian, German and Hungarian regions, but was not significant in the Italian, Spanish and Swedish regions. CONCLUSIONS: A 'processed' pattern and a 'healthy' pattern were found in most of the participating countries in the IDEFICS study, with comparable food item profiles. The results showed a strong inverse association of SES with the 'processed' pattern, suggesting that children of parents with lower SES may be at higher risk of unhealthy eating. Therefore, special focus should be given to parents and their children from lower SES levels when developing healthy eating promotion strategies.

Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis.

BACKGROUND: B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms. METHODS: We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts. RESULTS: Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection. CONCLUSIONS: This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.

B-vitamins intake, DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: the EPICOR study.

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.

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort.

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.

Validity of 24-h recalls in (pre-)school aged children: comparison of proxy-reported energy intakes with measured energy expenditure.

BACKGROUND & AIMS: Little is known about the validity of repeated 24-h dietary recalls (24-HDR) as a measure of total energy intake (EI) in young children. This study aimed to evaluate the validity of proxy-reported EI by comparison with total energy expenditure (TEE) measured by the doubly labeled water (DLW) technique. METHODS: The agreement between EI and TEE was investigated in 36 (47.2% boys) children aged 4-10 years from Belgium and Spain using subgroup analyses and Bland-Altman plots. Low-energy-reporters (LER), adequate-energy-reporters (AER) and high-energy-reporters (HER) were defined from the ratio of EI over TEE by application of age- and sex-specific cut-off values. RESULTS: There was good agreement between means of EI (1500 kcal/day) and TEE (1523 kcal/day) at group level though in single children, i.e. at the individual level, large differences were observed. Almost perfect agreement between EI and TEE was observed in thin/normal weight children (EI: 1511 kcal/day; TEE: 1513 kcal/day). Even in overweight/obese children the mean difference between EI and TEE was only -86 kcal/day. Among the participants, 28 (78%) were classified as AER, five (14%) as HER and three (8%) as LER. CONCLUSION: Two proxy-reported 24-HDRs were found to be a valid instrument to assess EI on group level but not on the individual level.