Associations between Fatty Acid Intakes and Plasma Phospholipid Fatty Acid Concentrations in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort (n = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels. RESULTS: Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain n-3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for n-3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)). CONCLUSIONS: Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions.

Protein and amino acid intakes in relation to prostate cancer risk and mortality-A prospective study in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: The association between protein intake and prostate cancer risk remains unclear. AIMS: To prospectively investigate the associations of dietary intakes of total protein, protein from different dietary sources, and amino acids with prostate cancer risk and mortality. METHODS: In 131,425 men from the European Prospective Investigation into Cancer and Nutrition, protein and amino acid intakes were estimated using validated dietary questionnaires. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a mean follow-up of 14.2 years, 6939 men were diagnosed with prostate cancer and 914 died of the disease. Dairy protein was positively associated with overall prostate cancer risk in the three highest fifths compared to the lowest (HRQ3 =1.14 (95% CI 1.05-1.23); HRQ 4=1.09 (1.01-1.18); HRQ5 =1.10 (1.02-1.19)); similar results were observed for yogurt protein (HRQ3 =1.14 (1.05-1.24); HRQ4 =1.09 (1.01-1.18); HRQ5 =1.12 (1.04-1.21)). For egg protein intake and prostate cancer mortality, no association was observed by fifths, but there was suggestive evidence of a positive association in the analysis per standard deviation increment. There was no strong evidence of associations with different tumour subtypes. DISCUSSION: Considering the weak associations and many tests, the results must be interpreted with caution. CONCLUSION: This study does not provide strong evidence for an association of intakes of total protein, protein from different dietary sources or amino acids with prostate cancer risk or mortality. However, our results may suggest some weak positive associations, which need to be confirmed in large-scale, pooled analyses of prospective data.

Associations between dietary amino acid intakes and blood concentration levels.

BACKGROUND AND AIMS: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations. RESULTS: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results. CONCLUSIONS: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.

Consumption of ultra-processed foods and drinks and colorectal, breast, and prostate cancer.

AIMS: To study whether the consumption of ultra-processed foods and drinks is associated with breast, colorectal, and prostate cancers. METHODS: Multicentric population-based case-control study (MCC-Spain) conducted in 12 Spanish provinces. Participants were men and women between 20 and 85 years of age with diagnoses of colorectal (n = 1852), breast (n = 1486), or prostate cancer (n = 953), and population-based controls (n = 3543) frequency-matched by age, sex, and region. Dietary intake was collected using a validated food frequency questionnaire. Foods and drinks were categorized according to their degree of processing based on the NOVA classification. Unconditional multivariable logistic regression was used to evaluate the association between ultra-processed food and drink consumption and colorectal, breast, and prostate cancer. RESULTS: In multiple adjusted models, consumption of ultra-processed foods and drinks was associated with a higher risk of colorectal cancer (OR for a 10% increase in consumption: 1.11; 95% CI 1.04-1.18). The corresponding odds for breast (OR 1.03; 95% CI 0.96-1.11) and prostate cancer (OR 1.02; 95% CI 0.93-1.12) were indicative of no association. CONCLUSIONS: Results of this large population-based case-control study suggest an association between the consumption of ultra-processed foods and drinks and colorectal cancer. Food policy and public health should include a focus on food processing when formulating dietary guidelines.

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study.

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a large-scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow-up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1-standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1-SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.

Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca's earthquakes (Murcia, Spain).

Information of the modulation effect of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on post-traumatic stress disorder (PTSD) after earthquakes is scarce and contradictory. A cross-sectional face-to-face interview survey of a representative sample of the adults was carried out after the Lorca (Spain) earthquakes (May 11, 2011). Socio-demographic variables, DSM-IV diagnostic assessment and earthquake-related stressors were obtained from the Composite International Diagnostic Interview (CIDI). The triallelic and biallelic classification of the 5-HTTLPR polymorphism were genotyped from buccal swabs. Multivariate logistic regression models were used to predict PTSD, including interaction terms to explore gene-environment (G x E) interactions. The vast majority (83%, n = 341) of the Lorca survey respondents (n = 412, 71% response rate) were genotyped. Both classifications of the 5-HTTLPR genotype were in Hardy-Weinberg equilibrium. Prior lifetime PTSD was the only variable that remained a significant predictor after adjustments. There were no significant main effects of earthquake related stressors or 5-HTTLPR. However, G x E interactions of 5-HTTLPR with high emotional impact and prior lifetime anxiety disorders were statistically significant. These results provide new evidence of the modulation effect of the 5-HTTLPR polymorphisms on PTSD risk. This information might characterize people at higher risk of developing PTSD after an earthquake exposure.

Domain-specific patterns of physical activity and risk of breast cancer sub-types in the MCC-Spain study.

PURPOSE: Literature on the separate effects of physical activities (PA) on risk of breast cancer (BC) sub-types is heterogeneous. We investigated domain-specific associations between PA and BC risk by menopausal status and molecular subtype. METHODS: 1389 histologically confirmed invasive BC cases and 1712 controls from the MCC-Spain study were included (age: 20-85 years). Questionnaire information on PA at work, at home, and during leisure time, including recreational PA and sedentary time, and data on reproductive history, anthropometry, family history of BC, diet, and lifestyles were obtained through face-to-face interviews. Information on the expression of oestrogen (ER), progesterone (PR), and HER2 receptors was available for > 95% of the cases. Mixed-effects multivariable logistic regression models were used to estimate odds ratios (OR) of BC sub-types. RESULTS: Occupational PA (OPA) intensity was associated with higher BC risk. Associations were stronger for pre-menopausal (ORactive/very active vs. sedentary job 1.89; 95% confidence interval (CI) 1.22, 2.91) and ER+/PR+, HER2- tumours (OR 1.80; 95% CI 1.28, 2.53). Sedentary time was associated with higher risk of post-menopausal BC (OR6-9 vs. <3 h/day 1.69; 95% CI 1.22, 2.32). Moderate-to-high-intensity household (HPA) and recreational PA (RPA) were inversely associated with BC occurrence in pre- and post-menopausal women, with estimated 14-33% lower risks (P for trend < 0.001) above 1000 MET·min/week. CONCLUSIONS: Higher levels of HPA and RPA were associated with lower risk of BC, with heterogeneity by molecular type, whereas sitting time was a consistent independent risk factor of BC risk. The positive association found for OPA with ER+/PR+ BC deserves further investigation.

Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition.

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study.

BACKGROUND & AIMS: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision. METHODS: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. RESULTS: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. CONCLUSIONS: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

Epidemiology of non-steroidal anti-inflammatory drugs consumption in Spain. The MCC-Spain study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. METHODS: Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. RESULTS: Women consumed more non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (< 45 years old) to 12.4% (≥75 years old). Aspirin was strongly associated with the presence of cardiovascular risk factors or established cardiovascular disease, reaching odds ratios of 15.2 (7.4-31.2) in women with acute coronary syndrome, 13.3 (6.2-28.3) in women with strokes and 11.1 (7.8-15.9) in men with acute coronary syndrome. Participants with cardiovascular risk factors or diseases consumed as much non-aspirin NSAID as participants without such conditions. CONCLUSIONS: Non-aspirin NSAIDs were more consumed by women and aspirin by men. The age patterns of aspirin and non-aspirin NSAIDs were opposite: the higher the age, the lower the non-aspirin NSAIDs usage and the higher the aspirin consumption. People with cardiovascular risk factors or diseases consumed more aspirin, but they did not decrease their non-aspirin NSAIDs usage.

Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins.

Importance: There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective: To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants: Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results: In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model. Conclusions and Relevance: This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

Prediction of acute myeloid leukaemia risk in healthy individuals.

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort.

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.

Meat and haem iron intake in relation to glioma in the European Prospective Investigation into Cancer and Nutrition study.

Diets high in red or processed meat have been associated positively with some cancers, and several possible underlying mechanisms have been proposed, including iron-related pathways. However, the role of meat intake in adult glioma risk has yielded conflicting findings because of small sample sizes and heterogeneous tumour classifications. The aim of this study was to examine red meat, processed meat and iron intake in relation to glioma risk in the European Prospective Investigation into Cancer and Nutrition study. In this prospective cohort study, 408 751 individuals from nine European countries completed demographic and dietary questionnaires at recruitment. Multivariable Cox proportional hazards models were used to examine intake of red meat, processed meat, total dietary iron and haem iron in relation to incident glioma. During an average follow-up of 14.1 years, 688 incident glioma cases were diagnosed. There was no evidence that any of the meat variables (red, processed meat or subtypes of meat) or iron (total or haem) were associated with glioma; results were unchanged when the first 2 years of follow-up were excluded. This study suggests that there is no association between meat or iron intake and adult glioma. This is the largest prospective analysis of meat and iron in relation to glioma and as such provides a substantial contribution to a limited and inconsistent literature.

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

Physical activity domains and risk of gastric adenocarcinoma in the MCC-Spain case-control study.

BACKGROUND: Evidence for a protective role of physical activity against development of stomach cancer is yet inconclusive. We studied the association of domain-specific physical activity and the risk of gastric adenocarcinoma (GAC), by site and histology, in the MCC-Spain case-control study. METHODS: 428 histologically confirmed GAC cases (67% men) including the gastro-esophageal region and 3225 controls were included. Cases were recruited in hospitals from 10 different Spanish regions, whereas population controls were randomly selected within the respective hospitals' catchment areas. A physical activity (PA) questionnaire was used to gather information on household and recreational activities, allowing estimation of PA volume (in metabolic equivalents (MET)-min/week). Participants also reported the intensity of working PA and daily sitting time. Questionnaire data on diet, lifestyles and clinical variables including Helicobacter pylori serology were available. Adjusted odds ratios (OR) of GAC were estimated for domains of physical activity, stratifying by sex, site (cardia vs. non-cardia), and Lauren classification (intestinal vs. diffuse). RESULTS: Household physical activity (HPA) showed a strong inverse association with GAC, observed for both cardia and non-cardia tumours. Risk of overall gastric cancer was 50% lower risk among participants in the highest HPA category (OR = 0.50, 95%CI: 0.38, 0.66). Recreational physical activity (RPA) was also associated with lower overall GAC risk (OR = 0.68, 95% CI: 0.52, 0.88), particularly at moderate levels of intensity such as walking (OR = 0.61, 95% CI: 0.46, 0.79). The protective effect of RPA was strongest for non-cardia tumours. Sedentary time was not related to GAC risk (p-trend = 0.392), but the potential protective effect of RPA was restricted to non-sedentary participants. CONCLUSIONS: Both household and recreational physical activities were independently related to lower GAC risk in the MCC-Spain study.

Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

BACKGROUND: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk. OBJECTIVE: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort. DESIGN: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs. RESULTS: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41). CONCLUSION: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.

Main nutrient patterns are associated with prospective weight change in adults from 10 European countries.

PURPOSE: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults. METHODS: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders. RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant. CONCLUSIONS: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.