Search

Background: The Airwave Health Monitoring Study aims to investigate the possible long-term health effects of Terrestrial Trunked Radio (TETRA) use among the police forces in Great Britain. Here, we investigate whether objective data from the network operator could be used to correct for misreporting in self-reported data and expand the radio usage availability in our cohort., Methods: We estimated average monthly usage of personal radio in the 12 months prior to enrolment from a missing value imputation model and evaluated its performance against objective and self-reported data. Factors associated with TETRA radio usage variables were investigated using Chi-square tests and analysis of variance., Results: The imputed data were better correlated with objective than self-reported usage (Spearman correlation coefficient = 0.72 vs. 0. 52 and kappa 0.56 [95% confidence interval 0.55, 0.56] vs. 0.46 [0.45, 0.47]), although the imputation model tended to under-estimate use for higher users. Participants with higher personal radio usage were more likely to be younger, men vs. women and officer vs. staff. The median average monthly usage level for the entire cohort was estimated to be 29.3 min (95% CI: [7.2, 66.6])., Conclusion: The availability of objective personal radio records for a large proportion of users allowed us to develop a robust imputation model and hence obtain personal radio usage estimates for ~50,000 participants. This substantially reduced exposure misclassification compared to using self-reported data and will allow us to carry out analyses of TETRA usage for the entire cohort in future work., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association., Methods and Results: Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant ( P <5×10 - 8 ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP ), rs7437940 ( AFAP1 ), rs13303 (missense, STAB1 ), and rs1055144 ( 7p15.2 ). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L ) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH ) was genome-wide significant., Conclusions: We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up., (© 2017 American Heart Association, Inc.)

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7 , TNXB , LRP12 , LOC283335 , SEPT9 , and AKT2 , and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA . Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10 -12 ). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption., Competing Interests: B. Psaty serves on the Data and Safety Monitoring Board for a clinical trial funded by the manufacturer (Zoll LifeCor) and the Steering Committee of the Yale Open Data Access project funded by Johnson & Johnson. D.J.M. serves on the scientific advisory board of Metacrine. The other authors report no competing financial interests.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention., Competing Interests: Conflict of interests N. P. has received financial support from several pharmaceutical companies that manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. S. K. has received Research Grant-Merck, Bayer, Aegerion; SAB-Catabasis, Regeneron Genetics Center, Merck, Celera; Equity-San Therapeutics, Catabasis; Consulting-Novartis, Aegerion, Bristol Myers-Squibb, Sanofi, AstraZeneca, Alnylam. P. Sever has received research awards from Pfizer Inc. A. Malarstig and M. Uria-Nickelsen are full time employees of Pfizer. D. Reily and M. Hoek are full time employees of Merck and co Inc. M.J. Caulfield is Chief Scientist for Genomics England a UK Government company. The authors declare no competing financial interest.

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.

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors., (Published by Elsevier Inc.)

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated., (Copyright © 2016 American Society of Human Genetics. All rights reserved.)

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases., (Copyright © 2016 American Society of Human Genetics. All rights reserved.)

Background: Terrestrial Trunked Radio (TETRA) is a digital communication system progressively adopted by Police Forces in Great Britain since 2001. In 2000, the UK Independent Expert Group on Mobile Phones suggested that exposure to TETRA-like signal modulation might have adverse effects on health. The Airwave Health Monitoring Study was established to investigate possible long-term effects of TETRA use on health. This requires estimation of TETRA use among Police Force employees participating in the study., Methods: We investigated TETRA usage among 42,112 Police officers and staff. An algorithm was created to link each personal radio user to his/her objective radio usage records for the 26,035 participants with available data. We linked 16,577 personal radio users to their objective radio usage records and compared self-reported usage with data from the TETRA operator for those individuals., Results: For weekly usage, the correlation between self-reported and operator-derived personal radio usage was r=0.69 for number and r=0.59 for the duration of calls. Compared with objective data, participants under-reported the number of calls and over-reported the duration of calls by a factor of around 4 and 1.6 respectively. Correlations were lower and bias higher when looking at daily usage., Conclusion: Where both objective and self-reported information were available, our study showed substantial misreporting in self-reported TETRA usage. Successful linkage of large numbers of TETRA users to objective data on their personal radios will allow objective assessment of TETRA radio usage for these participants and development of algorithms to correct bias in self-reported data for the remainder., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR = 1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR = 1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction = 0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear., (© 2014 UICC.)

Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α- and β-carotene, canthaxanthin, β-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α-, β- and γ- and δ-tocopherol) and dietary consumption of β-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary β-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties., (© 2014 UICC.)

Background: The Airwave Health Monitoring Study was established to evaluate possible health risks associated with use of TETRA, a digital communication system used by police forces and other emergency services in Great Britain since 2001. The study has been broadened to investigate more generally the health of the work force., Methods: From 2004, participants from each force who agreed to participate were enrolled either with an enrolment questionnaire or a comprehensive health screening performed locally. This includes questionnaire, 7-day food diaries, anthropometry, measurements of cardiovascular and cognitive function, blood chemistry, coagulation and haematology. Blood and urine samples are stored in vapour phase liquid nitrogen allowing long-term access for biochemical or genetic analysis. Access to the resource is via an access committee and a steering committee, including external scientific advisers as well as representatives of the police officers and staff., Results: By the end of 2012, the study had recruited 42,112 participants, of whom 35,199 (83.6%) had attended the health screening. Almost two thirds of participants were men and 71% of them were a TETRA user. Being in lower ranks (constable/sergeant and staff) was associated with a worse cardio-metabolic risk profile compared to higher ranks (inspector or chief inspector, superintendent and above)., Conclusion: The Airwave Health Monitoring Study is the only large-scale cohort study of police employees worldwide. The specificities of this sample, such as its well-defined job hierarchy, make it a particularly valuable occupational cohort. Participants have consented to the use of their data and samples for future, currently unspecified, research purposes., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Elevated systemic vascular stiffness is associated with increased risk of cardiovascular disease. It has been suggested that the time difference between the two characteristic peaks of the digital volume pulse (DVP) measured at the finger using photoplethysmography is related to the stiffness of the arterial tree, and inversely proportional to the stiffness index (SI). However, the precise physical meaning of the SI and its relation to aortic pulse wave velocity (aPWV) is yet to be ascertained. In this study we investigated numerically the effect of changes in arterial wall stiffness, peripheral resistances, peripheral compliances or peripheral wave reflections on the SI and aPWV. The SI was calculated from the digital area waveform simulated using a nonlinear one-dimensional model of pulse wave propagation in a 75-artery network, which includes the larger arteries of the hand. Our results show that aPWV is affected by changes in aortic stiffness, but the SI is primarily affected by changes in the stiffness of all conduit vessels. Thus, the SI is not a direct substitute for aPWV. Moreover, our results suggest that peripheral reflections in the upper body delay the time of arrival of the first peak in the DVP. The second peak is predominantly caused by the impedance mismatch within the 75 arterial segments, rather than by peripheral reflections.

Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC., (Copyright © 2013 UICC.)

Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence., Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death., Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis., Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease., Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.

Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. Only a few human studies have investigated the association between fish consumption and body-weight gain. We investigated the association between fish consumption and subsequent change in body weight. Women and men (n 344,757) participating in the European Prospective Investigation into Cancer and Nutrition were followed for a median of 5.0 years. Linear and logistic regression were used to investigate the associations between fish consumption and subsequent change in body weight. Among women, the annual weight change was 5.70 (95 % CI 4.35, 7.06), 2.23 (95 % CI 0.16, 4.31) and 11.12 (95 % CI 8.17, 14.08) g/10 g higher total, lean and fatty fish consumption per d, respectively. The OR of becoming overweight in 5 years among women who were normal weight at enrolment was 1.02 (95 % CI 1.01, 1.02), 1.01 (95 % CI 1.00, 1.02) and 1.02 (95 % CI 1.01, 1.04) g/10 g higher total, lean and fatty consumption per d, respectively. Among men, fish consumption was not statistically significantly associated with weight change. Adjustment for potential over- or underestimation of fish consumption did not systematically change the observed associations, but the 95 % CI became wider. The results in subgroups from analyses stratified by age or BMI at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption has no appreciable association with body-weight gain.

Background: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide. In high-income countries, low socioeconomic status seems to be related to a high incidence of T2DM, but very little is known about the intermediate factors of this relationship. Method We performed a case-cohort study in eight Western European countries nested in the EPIC study (n = 340, 234, 3.99 million person-years of follow-up). A random sub-cohort of 16,835 individuals and a total of 12,403 incident cases of T2DM were identified. Crude and multivariate-adjusted hazard ratios (HR) were estimated for each country and pooled across countries using meta-analytical methods. Age-, gender- and country-specific relative indices of inequality (RII) were used as the measure of educational level and RII tertiles were analysed., Results: Compared with participants with a high educational level (RII tertile 1), participants with a low educational level (RII tertile 3) had a higher risk of T2DM [HR: 1.77, 95% confidence interval (CI): 1.69-1.85; P-trend < 0.01]. The HRs adjusted for physical activity, smoking status and propensity score according to macronutrient intake were very similar to the crude HR (adjusted HR: 1.67, 95% CI: 1.52-1.83 in men; HR: 1.88, 95% CI: 1.73-2.05 in women). The HRs were attenuated only when they were further adjusted for BMI (BMI-adjusted HR: 1.36, 95% CI: 1.23-1.51 in men; HR: 1.32, 95% CI: 1.20-1.45 in women)., Conclusion: This study demonstrates the inequalities in the risk of T2DM in Western European countries, with an inverse relationship between educational level and risk of T2DM that is only partially explained by variations in BMI.

Background: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence., Objective: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Design: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models., Results: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers., Conclusion: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.

Background: Fruit and vegetable consumption might prevent weight gain through their low energy density and high dietary fiber content., Objective: We assessed the association between the baseline consumption of fruit and vegetables and weight change in participants from 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition study., Design: Diet was assessed at baseline in 373,803 participants by using country-specific validated questionnaires. Weight was measured at baseline and self-reported at follow-up in most centers. Associations between baseline fruit and vegetable intakes (per 100 g/d) and weight change (g/y) after a mean follow-up of 5 y were assessed by using linear mixed-models, with age, sex, total energy intake, and other potential confounders controlled for., Results: After exclusion of subjects with chronic diseases at baseline and subjects who were likely to misreport energy intakes, baseline fruit and vegetable intakes were not associated with weight change overall. However, baseline fruit and vegetable intakes were inversely associated with weight change in men and women who quit smoking during follow-up. We observed weak positive associations between vegetable intake and weight change in women who were overweight, were former smokers, or had high prudent dietary pattern scores and weak inverse associations between fruit intake and weight change in women who were >50 y of age, were of normal weight, were never smokers, or had low prudent dietary pattern scores., Conclusions: In this large study, higher baseline fruit and vegetable intakes, while maintaining total energy intakes constant, did not substantially influence midterm weight change overall but could help to reduce risk of weight gain in persons who stop smoking. The interactions observed in women deserve additional attention.

Objectives: Web-based studies nowadays raise a major interest as they can improve all steps involved in observational studies. Our objective was to compare the web-based version of the NutriNet-Santé self-administered socio-demographic and economic questionnaire with the traditional paper version., Methods: Both versions of the questionnaire were sent to 170 volunteers and filled in by 147 of them (either paper first, n = 76, or web-based first, n = 71). Agreement between versions was assessed by intraclass correlations (ICC) and kappas., Results: Agreement between both versions was high, with ICC and kappas ranging between 0.81-1.00 and 0.76-1.00, respectively, similarly across groups of administration order, age, gender and self-estimated web knowledge in general. The web-based version was the one preferred by 93.7% of the subjects and enabled to avoid 553 missing values (2.00% of the total entries), 24 inconsistent data (0.09%), 8 aberrant data (0.03%), 472 data entry errors (0.85%) and to save 2,800 (US $4,072) when sent to 170 subjects., Conclusion: The web-based socio-demographic and economic questionnaire provided information of similar-to-superior quality compared to the traditional paper version, with substantial logistic and cost advantages.

Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.

The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.

Background: There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases. However, it is not clear whether this dietary pattern may be protective also against the development of obesity., Objective: We assessed the association between the adherence to the Mediterranean dietary pattern (MDP), prospective weight change, and the incidence of overweight or obesity., Design: We conducted a prospective cohort study [the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455 men and 270,348 women; age range: 25-70 y) from 10 European countries. Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range: 0-18) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet. The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression., Results: Individuals with a high adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight change of -0.16 kg (95% CI: -0.24, -0.07 kg) and were 10% (95% CI: 4%, 18%) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain., Conclusion: This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity.

Background: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results., Objective: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project., Design: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders., Results: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat., Conclusion: Our results suggest that a decrease in meat consumption may improve weight management.

Nutritional recommendations call for balanced, diversified consumption of starchy foods and increased whole-grain food intake. Their efficiency may depend on sociodemographic and socioeconomic factors, for which little information is available. The aim of the present study was to investigate the relationship between sociodemographic and socioeconomic characteristics and starchy food consumption in a large general population of French adults. Dietary intake was assessed using at least six 24-h dietary records collected, during a 2-year period, from 4574 men and women aged 45-60 years who participated in the Supplémentation en VItamines Minéraux et AntioXydants cohort study in 1995-7. Compliance with the recommendation ( > or = 3 and < 6 servings/d), non-consumption of whole-grain products, variety and daily cost were compared across sociodemographic and socioeconomic categories using logistic regression and covariance analyses. About 55 % of subjects complied with the starchy food recommendation, with little variation across sociodemographic characteristics. Consumption of whole-grain products was less likely in men (P = 0.001), in subjects with a lower education level (P-trend = 0.01) and in those belonging to intermediate occupational categories (P = 0.02). The variety of starchy food intake increased with education level (P-trend = 0.0002) and was lowest for manual workers (P = 0.03). The proportion of daily food cost spent on starchy foods decreased with occupational category (P < 0.0001), and was higher in rural areas (P = 0.0004). The starchy food budget spent on potatoes decreased with the educational level (P-trend = 0.007), whereas it increased for rice and unsweetened breakfast cereals (P-trend = 0.001 for both). Public recommendations concerning starchy food variety and whole-grain intake should specifically target subjects with a lower education level and/or occupational category.

Background: Limited observational evidence suggests lower antioxidant concentrations in individuals with the metabolic syndrome (MetS); few randomized controlled trials have addressed the effect of multiple antioxidants on the risk of MetS., Objective: The objective was to examine the effect of antioxidant supplementation for 7.5 y on the incidence of MetS and the epidemiologic association between baseline serum antioxidant concentrations and the prospective risk of MetS., Design: Adults (n = 5220) participating in the SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) primary prevention trial were randomly assigned to receive a supplement containing a combination of antioxidants (vitamins C and E, beta-carotene, zinc, and selenium) at nutritional doses or a placebo. Subjects were free of MetS at baseline and were followed for 7.5 y., Results: Antioxidant supplementation for 7.5 y did not affect the risk of MetS. Baseline serum antioxidant concentrations of beta-carotene and vitamin C, however, were negatively associated with the risk of MetS; the adjusted odds ratios (and 95% CIs) for the highest compared with the lowest tertile were 0.34 (0.21, 0.53; P for trend = 0.0002) and 0.53 (0.35, 0.80; P for trend = 0.01), respectively. Baseline serum zinc concentrations were positively associated with the risk of developing MetS; the adjusted odds ratio (and 95% CI) for the highest compared with the lowest tertile was 1.81 (1.20, 2.72; P for trend = 0.01)., Conclusions: The experimental finding of no beneficial effects of antioxidant supplementation in a generally well-nourished population is consistent with recent reports of a lack of efficacy of antioxidant supplements. However, the relations observed between the risk of MetS and baseline serum antioxidant concentrations, which probably reflect associations with overall dietary patterns, do support the current recommendations to consume antioxidant-rich foods. This trial was registered at clinicaltrials.gov as NCT00272428.

Objective: The overall trend of obesity prevalence has increased during the last decades, even in France which has one of the lowest prevalence in Europe. The aim of this study was to assess, according to socioeconomic status (SES), whether a shift in the obesity prevalence trends could be observed since the French National Nutrition and Public Health Program was implemented in 2001., Methods: Standardised cross-sectional repeated population-based data from the French Social Security Health Examination Centers in the central-western region of France (n=339,882). We examined regression slopes (95% CI) of overall and abdominal obesity from 1995 to 2005 according to SES. We also compared slopes within each SES between 1995-2001 and 2001-2005., Results: After standardisation to the French age distribution, 6.9% of men and 6.4% of women were obese in 1995 and 8.9% and 8.6% in 2005, respectively. Abdominal adiposity concerned 5.6% of men and 8.5% of women in 1995 and 9.5% and 14.3% in 2005. Obesity prevalence regression slopes between 1995 and 2005 increased in all SES categories, except management professionals in both genders and office/service personnel male who were stable. Significant regression slopes before 2001 became non-significant afterward in office/service personnel males for obesity prevalence; and for abdominal obesity in manual workers women and office/service personnel (p=0.05, in men)., Conclusions: Our data confirm the overall epidemic rise in the obesity prevalence trends during the last decade, except in management professionals and office/service personnel men. Obesity prevalence trends in office/service personnel and manual workers women for abdominal obesity were also observed to stabilise since 2001. We could hypothesize that the National Nutrition and Public Health Program may partly be involved in this decreasing trend among office/service personnel mainly. Policymakers should take into account these data to assess the effectiveness of obesity prevention public-health strategies in the future.

Background: Some studies have shown an inverse relation between calcium intake and body weight or fat mass., Objective: We aimed to investigate the relations of dairy consumption and calcium intake with 6-y changes in body weight and waist circumference (WC)., Design: Multivariate analysis of variance according to dairy consumption or calcium intake quartile was presented, stratified by sex and body weight status at baseline, in 2267 middle-aged French adults., Results: The associations between dairy products and anthropometric changes differed according to sex and overweight status at baseline. In overweight men only, 6-y changes in weight and WC were inversely associated with the consumption of dairy products-especially that of milk (P = 0.02 for both weight and WC changes) and yogurt (P = 0.01 and 0.03 for weight and WC changes, respectively). No relation was observed with cheese and calcium intake. Positive relations were found between milk consumption and WC change in overweight women and between yogurt consumption and weight change in normal-weight women. Multivariate analyses showed a trend toward increases in weight with high dairy calcium intakes in normal-weight women., Conclusions: The relation of dairy products and calcium intake with changes in weight and WC may differ according to sex, initial body-weight status, and type of dairy products. The negative association between dairy products and anthropometric changes observed in overweight men was not explained by dairy calcium intakes, which suggests that other components of dairy products or specific dietary patterns associated with dairy consumption may help to explain the observed associations.

Background: Body mass index (BMI) and waist circumference (WC) are increased in subjects chronically treated for hypertension. However, the relationships of BMI, WC and metabolic syndrome (MS) with central wave reflections and pulse pressure (PP) amplification have never been investigated., Methods: A cohort of 517 treated hypertensives was studied cross-sectionally as function of BMI, WC and presence of MS, the latter used as index of insulin resistance. In men and women, carotid wave reflections were evaluated using pulse wave analysis and augmentation index measurement. PP amplification between brachial and carotid arteries was determined as a vascular factor contributing to protect against an increased afterload., Results: When compared to their own controls, treated hypertensive subjects with increased BMI, WC or MS did not differ in terms of mean values of brachial and carotid blood pressure and augmentation index. However, they were characterized by increased heart rate (HR) and PP amplification. Such results were independent of age, drug treatment, and traditional cardiovascular risk factors. After HR adjustment, the increased PP amplification observed in subjects with high WC or MS became non-significant in men, but remained unmodified in women. The presence of beta-blockade did not modify the result., Conclusion: In treated hypertensive subjects, adiposity and insulin sensitivity influence independently PP amplification. The finding is observed mainly in women.

Background: Dietary fruits and vegetables may enhance iron status because of their high vitamin C content. The potential association between iron status and intakes of specific fruits and vegetables, according to sex and menopausal status, must be investigated., Objective: The objective was to assess the relation between dietary fruits, vegetables, and juices (FVJ) according to their vitamin C and fiber contents and serum ferritin and hemoglobin concentrations., Design: A total of 4358 subjects, aged 35-60 y, of the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) cohort were selected. Subjects had completed at least six 24-h-dietary records over 2 y. The relation between serum ferritin and hemoglobin, measured at inclusion, and dietary FVJ according to their vitamin C and fiber contents was assessed by multiple regression analysis., Results: In premenopausal women, serum ferritin was positively associated with intakes of fiber-poor FVJ (up to 10% higher serum ferritin in the third tertile compared with the first tertile). In the whole sample, hemoglobin was positively associated with fruits, vitamin C-rich FVJ, FVJ ascorbic acid, and fiber-poor FVJ categories (up to 1.5 g/L higher hemoglobin concentration)., Conclusions: Intakes of fiber-poor FVJ were associated with higher serum ferritin concentrations in premenopausal women and with higher hemoglobin concentrations in the whole sample. Our results suggest that the fiber content of fruits and vegetables influences iron stores in premenopausal women but has no influence in groups in whom nonheme-iron absorption is limited because of high iron stores. Other mechanisms are likely to be involved in the case of hemoglobin.

Background: Although short-term effects of the Dietary Approaches to Stop Hypertension (DASH) diet on blood pressure have been shown in intervention studies, less is known about the long-term effects., Objective: The aim was to study the relation between dietary patterns based on DASH diet characteristics and blood pressure (BP) and BP change in a clinical trial of antioxidants conducted in France from 1994 to 2002., Design: Repeated 24-h dietary records were collected during the first year of follow-up. Dietary variables studied included fruit and vegetables, dairy products and fat (defined by Keys score), and two hypothesis-oriented scores based on the DASH diet. We performed a cross-sectional analysis of BP measured at the first clinical examination (1995-1996) in 4652 participants aged 35-63 y and a longitudinal analysis of BP change over a median follow-up of 5.4 y (n = 2341)., Results: The mean increases in systolic (SBP) and diastolic (DBP) BPs were 9.3 and 4.5 mm Hg, respectively. After adjustment for potential confounders, higher fruit and vegetable consumption was associated with lower SBP and DBP at first clinical examination (P for trend < 0.02 for both) and a lower 5-y increase in SBP (-2.1 mm Hg in the 4th compared with the 1st quartile; P for trend < 0.004) and DBP (-0.7 mm Hg in the 4th compared with the 1st quartile; P for trend < 0.03). The 2 DASH scores also were significantly associated with a lower BP at the first clinical examination and a lower BP increase. No significant relations were observed with dairy products or Keys score in either analyses., Conclusion: These results suggest that high fruit and vegetable intakes may be associated with a lower increase in BP with aging.

Background: Observational data suggest a protective effect of several antioxidants on fasting plasma glucose (FPG) and type 2 diabetes. However, randomized trials have yielded inconsistent results., Objectives: The first objective was to assess the effect of 7.5 y of antioxidant supplementation on FPG at 7.5 y. The second objective was to examine the epidemiologic association of baseline dietary intakes or plasma antioxidants and FPG (at baseline and at 7.5 y)., Design: Subjects (n = 3146) from the Supplementation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) primary prevention trial in France were randomly assigned to receive a daily capsule containing 120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 mug Se, and 20 mg Zn or a placebo., Results: After 7.5 y, no significant difference was observed between age-adjusted mean FPG in men (P = 0.78) and women (P = 0.89) in either group. Baseline beta-carotene dietary intakes and plasma concentrations were inversely associated with FPG in multivariate mixed models (P = 0.0045 and P < 0.0001, respectively). Baseline plasma vitamin C and selenium were negatively (P = 0.0455) and positively (P < 0.0001) associated, respectively, with FPG., Conclusions: Supplementation with antioxidants at nutritional doses for 7.5 y had no effect on FPG in men or women who followed a balanced diet. An inverse association of baseline beta-carotene dietary intake and plasma concentrations with FPG was found, probably because beta-carotene is an indirect marker of fruit and vegetable intakes.