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.

Adherence to a healthy Nordic food index and risk of myocardial infarction in middle-aged Danes: the diet, cancer and health cohort study.

BACKGROUND/OBJECTIVES: For decades, the Mediterranean diet has been in focus regarding healthy eating as it has been associated with reduced risk of non-communicable diseases. Less interest has been given to health benefits of other regional diets. The aim of the present study was to assess whether adherence to a healthy Nordic food index was associated with lower risk of myocardial infarction (MI) among middle-aged Danes. SUBJECTS/METHODS: Data were obtained from the Danish Diet, Cancer and Health cohort study of 57 053 men and women aged 50-64 years recruited between 1993 and 1997. The healthy Nordic food index comprised healthy Nordic food items selected a priori (fish, cabbage, rye bread, oatmeal, apple and pears and root vegetables). Information on incident MI was ascertained through linkage with national registries. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated from sex-specific Cox proportional hazard models. RESULTS: In total, 1669 men and 653 women developed MI during follow-up (13.6 median years). In adjusted models, those with an index score of 5-6 points (highest scores) had significantly lower MI risk (men: HR=0.77, 95% CI=0.62, 0.97; women: HR=0.55, 95% CI=0.37, 0.82) relative to those scoring 0 points in the index (lowest score). A significantly lower MI risk was found per 1-point increment in the index in both men (HR=0.95, 95% CI=0.92, 0.99) and women (HR=0.93, 95% CI=0.88, 0.98). CONCLUSIONS: A healthy Nordic diet is associated with lower MI risk among middle-aged Danes, suggesting that Nordic diets should be considered in recommendations for dietary changes in the promotion of coronary health.

Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta-analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between-study heterogeneity was assessed using I(2) statistics. Overall, the summary RR (95% CI) was 1.22 (1.14-1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I(2) = 21.2%). In a dose-response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%-5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.

Dietary patterns derived with multiple methods from food diaries and breast cancer risk in the UK Dietary Cohort Consortium.

BACKGROUND/OBJECTIVES: In spite of several studies relating dietary patterns to breast cancer risk, evidence so far remains inconsistent. This study aimed to investigate associations of dietary patterns derived with three different methods with breast cancer risk. SUBJECTS/METHODS: The Mediterranean Diet Score (MDS), principal components analyses (PCA) and reduced rank regression (RRR) were used to derive dietary patterns in a case-control study of 610 breast cancer cases and 1891 matched controls within four UK cohort studies. Dietary intakes were collected prospectively using 4- to 7-day food diaries and resulting food consumption data were grouped into 42 food groups. Conditional logistic regression models were used to estimate odds ratios (ORs) for associations between pattern scores and breast cancer risk adjusting for relevant covariates. A separate model was fitted for post-menopausal women only. RESULTS: The MDS was not associated with breast cancer risk (OR comparing first tertile with third 1.20 (95% CI 0.92; 1.56)), nor the first PCA-derived dietary pattern, explaining 2.7% of variation of diet and characterized by cheese, crisps and savoury snacks, legumes, nuts and seeds (OR 1.18 (95% CI 0.91; 1.53)). The first RRR-derived pattern, a 'high-alcohol' pattern, was associated with a higher risk of breast cancer (OR 1.27; 95% CI 1.00; 1.62), which was most pronounced in post-menopausal women (OR 1.46 (95% CI 1.08; 1.98)). CONCLUSIONS: A 'high-alcohol' dietary pattern derived with RRR was associated with an increased breast cancer risk; no evidence of associations of other dietary patterns with breast cancer risk was observed in this study.

Baseline patterns of adipose tissue fatty acids and long-term risk of breast cancer: a case-cohort study in the Danish cohort Diet, Cancer and Health.

BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.

Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study.

AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. RESULTS: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.

Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study.

Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification.

Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis.

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.

Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition.

Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79-0.97 and 0.76; 95% CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.

Vitamin C intake from diary recordings and risk of breast cancer in the UK Dietary Cohort Consortium.

BACKGROUND/OBJECTIVES: Vitamin C intake has been inversely associated with breast cancer risk in case-control studies, but not in meta-analyses of cohort studies using Food Frequency Questionnaires, which can over-report fruit and vegetable intake, the main source of vitamin C. This is the first study to investigate associations between vitamin C intake and breast cancer risk using food diaries. SUBJECTS/METHODS: Estimated dietary vitamin C intake was derived from 4-7 day food diaries pooled from five prospective studies in the UK Dietary Cohort Consortium. This nested case-control study of 707 incident breast cancer cases and 2144 matched controls examined breast cancer risk in relation to dietary vitamin C intake using conditional logistic regression adjusting for relevant covariates. Additionally, total vitamin C intake from supplements and diet was analysed in three cohorts. RESULTS: No evidence of associations was observed between breast cancer risk and vitamin C intake analysed for dietary vitamin C intake (odds ratios (OR)=0.98 per 60 mg/day, 95% confidence interval (CI): 0.88-1.09, P (trend)=0.7), dietary vitamin C density (OR=0.97 per 60 mg/day, 95% CI: 0.87-1.07, P (trend)=0.5 ) or total vitamin C intake (OR=1.01 per 60 mg/day, 95% CI: 0.99-1.03, P (trend)=0.3). Additionally, there was no significant association for post-menopausal women (OR=1.02 per 60 mg/day, 95% CI: 0.99-1.05, P (trend)=0.3). CONCLUSIONS: This pooled analysis of individual UK women found no evidence of significant associations between breast cancer incidence and dietary or total vitamin C intake derived uniquely from detailed diary recordings.

Mediterranean dietary pattern and cancer risk in the EPIC cohort.

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.

Alcohol intake and risk of colorectal cancer: results from the UK Dietary Cohort Consortium.

BACKGROUND: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent. METHODS: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ). RESULTS: Compared with individuals in the lightest category of drinkers (>0-<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5-<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15-<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30-<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with >or=45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results. CONCLUSION: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium.

Disulphide formation on mitochondrial protein thiols.

A large number of proteins contain free thiols that can be modified by the formation of internal disulphides or by mixed disulphides with low-molecular-mass thiols. The majority of these latter modifications result from the interaction of protein thiols with the endogenous glutathione pool. Protein glutathionylation and disulphide formation are of significance both for defence against oxidative damage and in redox signalling. As mitochondria are central to both oxidative damage and redox signalling within the cell, these modifications of mitochondrial proteins are of particular importance. In the present study, we review the mechanisms and physiological significance of these processes.