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Background: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse. Methods: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142 605 men and 335 873. Adherence to Mediterranean diet was examined using a score (range: 0–9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders. Results: In all, 9669 incident cancers in men and 21 062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95–0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern. Conclusion: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53–0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54–1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.

Background/objectives: High intakes of unprocessed red or processed meat may increase the risk of stroke. We aimed to examine the association between unprocessed red meat, processed meat and total red meat consumption and risk of total stroke and ischaemic stroke., Subjects/methods: Cox proportional hazards regression analyses were conducted based on the data for 41,020 men and women aged 29-69 years at baseline., Results: During a mean follow-up of 13.8 years, 674 incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42 subarachnoid haemorrhages and 22 mixed or unspecified events) were identified. After multiple adjustment, unprocessed red meat, processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P-trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI 0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57-1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82 (95% CI 0.47-1.42; P-trend=0.31) in women., Conclusions: In the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women.

Background/objectives: Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D., Subjects/methods: A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12,403 incident T2D cases and a subcohort of 16,835 people, identified from a cohort of 340,234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis., Results: After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D., Conclusions: Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.

Background/objectives: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations., Subjects/methods: A nested case-control study (1269 cases matched to 2107 controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors., Results: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P(diff)<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption (P(interaction)=0.07)., Conclusions: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism.

Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16,154 participants and 12,403 incident cases of T2D were identified from 340,234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.

Background/objectives: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study., Subjects/methods: Participants were 306,331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall., Results: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P=0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07)., Conclusion: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.

Background/objectives: The relation between lifetime use of alcohol and measures of abdominal and general adiposity is unknown., Subjects/methods: Among 99,381 men and 158,796 women of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, means of waist circumference (WC), waist-to-hip-ratio (WHR) and body mass index (BMI), and odds ratios (OR) for a larger WC than predicted for a given BMI (WClp=positive residuals of gender specific linear regression of BMI on WC) across categories of average lifetime use of alcohol (total, from wine and from beer) were calculated, all adjusted for socio-demographic, lifestyle and health factors., Results: WC, WHR and BMI in men using lifetime ≤6 g/d alcohol were 95.1 cm, 0.942 and 27.3 kg/m(2), and 96.2 cm, 0.961 and 28.3 kg/m(2) when using >96 g/d. WC and WHR in women was 83.2 cm and 0.813 for ≤6 g/d, and 84.6 cm and 0.830 for >60 g/d, whereas BMI deviated only slightly with the lowest BMI (26.7 kg/m(2)) observed for >6-24 g/d. Compared with ≤6 g/d, OR for a WClp in both genders increased steadily across categories of alcohol use (up to 1.40 (95% confidence interval 1.32, 1.49) in men using >60 g/d and 1.63 (1.54, 1.73) in women using >24 g/d), though increase was higher for alcohol from beer than from wine (P for difference between beer and wine<0.001 (men) and=0.002 (women))., Conclusion: Lifetime alcohol use is positively related to abdominal and general adiposity in men, possibly following the male weight gain pattern; in women, it is positively related only to abdominal adiposity. In this context, beer may contribute additionally to abdominal adiposity.

Previous results suggested a potential role for T-cell protein tyrosine phosphatase (TC-PTP) in cell proliferation. However, no conclusive data has supported such a function in the modulation of this process. In order to clarify this issue, we isolated TC-PTP-/- murine embryonic fibroblasts (MEFs) as well as cell lines to characterize the role of TC-PTP in the control of cell proliferation and cell cycle. Both TC-PTP-/- primary MEFs and cell lines proliferate slower than TC-PTP+/+ cells. We also demonstrated that TC-PTP-/- cells have a slow progression through the G1 phase of the cell cycle. Further characterization of the G1 defect indicates that the kinetics of cyclin D1 induction was delayed and that p27(KIP1) remains at higher levels for an extended period of time. Moreover, cells lacking TC-PTP showed a delayed activation of CDK2. This slow progression through the early G1-phase resulted in decreased phosphorylation of the RB protein and subsequent delay into the S phase transition. In contrast, no further defects were detected in other phases of the cell cycle. Survey of the potential signaling pathways leading to this delayed cyclin D1 expression indicated that NF-kappaB activation was compromised and that IKKbeta activity was also reduced following PDGF stimulation. Reintroduction of wild-type TC-PTP into the TC-PTP-/- cells rescued the defective proliferation, cyclin D1 expression, NF-kappaB activation as well as IkappaB phosphorylation. Together, these results confirm that TC-PTP plays a positive role in the progression of early G1 phase of the cell cycle through the NF-kappaB pathway.