Showing papers by "Heiner Boeing published in 2016"
Mariachiara Di Cesare1, Mariachiara Di Cesare2, James Bentham2, Gretchen A Stevens3 +738 more•Institutions (60)
TL;DR: The posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue, is calculated.
3,766 citations
James Bentham1, Mariachiara Di Cesare2, Mariachiara Di Cesare1, Gretchen A Stevens3 +787 more•Institutions (246)
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
1,348 citations
Christian Fuchsberger1, Christian Fuchsberger2, Jason Flannick3, Jason Flannick4 +346 more•Institutions (77)
TL;DR: In this paper, the authors performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing for 12,940 individuals from five ancestry groups.
Abstract: The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
866 citations
01 Jan 2016
TL;DR: Large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes, but most fell within regions previously identified by genome-wide association studies.
Abstract: The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
698 citations
International Agency for Research on Cancer1, Aarhus University2, South University3, Institut Gustave Roussy4, German Cancer Research Center5, Academy of Athens6, Prevention Institute7, Utrecht University8, Imperial College London9, University of Tromsø10, University of Oslo11, University of Granada12, Lund University13, Umeå University14, Karolinska Institutet15, Swedish University of Agricultural Sciences16, University of Oxford17, University of Cambridge18
TL;DR: The large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries are described.
Abstract: Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.
297 citations
University of Cambridge1, Basque Government2, University of Paris-Sud3, French Institute of Health and Medical Research4, Lund University5, Umeå University6, University of Oxford7, University of Murcia8, Aalborg University9, Prevention Institute10, University of Naples Federico II11, Imperial College London12, University of Granada13, International Agency for Research on Cancer14, Utrecht University15, University of Glasgow16
TL;DR: Exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes and coronary artery disease, according to a meta-analysis of genetic association studies.
Abstract: IMPORTANCE Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are associated with the risk of type 2 diabetes. OBJECTIVE To investigate whether LDL-C-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016. EXPOSURES Low-density lipoprotein cholesterol-lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) for type 2 diabetes and coronary artery disease. RESULTS Low-density lipoprotein cholesterol-lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95%CI, 0.42-0.88]; P = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95%CI, 1.70-3.43]; P .001). For PCSK9 genetic variants, the OR for type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19 (95%CI, 1.02-1.38; P = .03). For a given reduction in LDL-C, genetic variants were associated with a similar reduction in coronary artery disease risk (I2 = 0%for heterogeneity in genetic associations; P = .93). However, associations with type 2 diabetes were heterogeneous (I2 = 77.2%; P = .002), indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles. CONCLUSIONS AND RELEVANCE In thismeta-analysis, exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other geneswas associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy.
293 citations
TL;DR: The NutriGrade scoring system showed good agreement and reliability, and the initial findings regarding the performance of this newly established scoring system need further evaluation in independent analyses.
208 citations
TL;DR: A diet imbalance with high consumption of sugar and soft drinks and low consumption of vegetables was associated with UC risk, and further studies are needed to investigate whether microbiota alterations or other mechanisms mediate this association.
Abstract: Background: Specific nutrients or foods have been inconsistently associated with ulcerative colitis (UC) or Crohn’s disease (CD) risks. Thus, we investigated associations between diet as a whole, a ...
187 citations
TL;DR: This study comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation.
Abstract: Aim: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure. Materials & methods: Here, we examined the potential of DNA methylation changes in 910 prediagnostic peripheral blood samples as a marker of exposure to tobacco smoke in a large multinational cohort. Results: We identified 748 CpG sites that were differentially methylated between smokers and nonsmokers, among which we identified novel regionally clustered CpGs associated with active smoking. Importantly, we found a marked reversibility of methylation changes after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation. Conclusion: Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation.
175 citations
TL;DR: Changes in blood lipid composition precede the diagnosis of common malignancies by several years and point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.
Abstract: First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk. Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835 incident cancer cases. The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis. Changes in blood lipid composition precede the diagnosis of common malignancies by several years. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.
158 citations
University of Cambridge1, MRC Human Nutrition Research2, Utrecht University3, Wageningen University and Research Centre4, French Institute of Health and Medical Research5, Institut Gustave Roussy6, Basque Government7, Lund University8, Umeå University9, University of Oxford10, Aalborg University11, Aarhus University12, Prevention Institute13, University of Naples Federico II14, University of Granada15, University of Turin16, International Agency for Research on Cancer17, University of Murcia18, Imperial College London19
TL;DR: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D.
Abstract: Background: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88–0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77–0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85–0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. Conclusions: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.
01 Jun 2016
TL;DR: A low-frequency missense variant in the gene encoding glucagon-like peptide-1 receptor, the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP 1R agonist therapies, and provided evidence that GLP2D agonists are not likely to be associated with an unacceptable increase in cardiovascular risk.
Abstract: Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
TL;DR: The winter or the post-harvest season is associated with increased energy intake and the intake of fruits, vegetables, eggs, meat, cereals and alcoholic beverages is following a seasonal consumption pattern and at least for these foods season is determinant of intake.
Abstract: The aim of this systematic review and meta-analysis was to assess the effect of season on food intake from selected food groups and on energy intake in adults. The search process was based on selecting publications listed in the following: Medline, Scopus, Web of Science, Embase and Agris. Food frequency questionnaires, 24-h dietary recalls and food records as methods for assessment of dietary intake were used to assess changes in the consumption of 11 food groups and of energy intake across seasons. A meta-analysis was performed. Twenty-six studies were included. Articles were divided into those reporting data on four seasons (winter, spring, summer and autumn) or on two seasons (pre-and post-harvest). Four of the studies could be utilized for meta-analysis describing changes in food consumption across four season scheme: from winter to spring fruits decreased, whereas vegetables, eggs and alcoholic beverages increased; from spring to summer vegetable consumption further increased and cereals decreased; from summer to autumn fruits and cereals increased and vegetables, meat, eggs and alcoholic beverages decreased; from autumn to winter cereals decreased. A significant association was also found between energy intake and season, for 13 studies reporting energy intake across four seasons (favors winter) and for eight studies across pre- and post-harvest seasons (favors post-harvest). The winter or the post-harvest season is associated with increased energy intake. The intake of fruits, vegetables, eggs, meat, cereals and alcoholic beverages is following a seasonal consumption pattern and at least for these foods season is determinant of intake.
TL;DR: Evidence is added which supports the energy density of food as a simple but effective measure to manage weight in the obese with the aim of weight reduction.
Abstract: Regulating the energy density of food could be used as a novel approach for successful body weight reduction in clinical practice. The aim of this study was to conduct a systemic review of the literature on the relationship between food energy density and body weight changes in obese adults to obtain solid evidence supporting this approach. The search process was based on the selection of publications in the English language listed in public databases. A meta-analysis was performed to combine individual study results. Thirteen experimental and observational studies were identified and included in the final analysis. The analyzed populations consist of 3628 individuals aged 18 to 66 years. The studies varied greatly in terms of study populations, study design and applied dietary approaches. The meta-analysis revealed a significant association between low energy density foods and body weight reduction, i.e., −0.53 kg when low energy density foods were eaten (95% CI: −0.88, −0.19). In conclusions, this study adds evidence which supports the energy density of food as a simple but effective measure to manage weight in the obese with the aim of weight reduction.
Utrecht University1, Oklahoma State University Center for Health Sciences2, Imperial College London3, Wageningen University and Research Centre4, Aarhus University5, International Agency for Research on Cancer6, French Institute of Health and Medical Research7, German Cancer Research Center8, National and Kapodistrian University of Athens9, Academy of Athens10, Harvard University11, University of Naples Federico II12, Prevention Institute13, University of Tromsø14, University of Murcia15, Andalusian School of Public Health16, Lund University17, Umeå University18, Cancer Epidemiology Unit19, University of Cambridge20
TL;DR: It is indicated that higher concentrations of plasma β-carotene and α- carotene are associated with lower breast cancer risk of ER- tumors and no statistically significant interaction between smoking, alcohol, or BMI is observed.
TL;DR: The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data.
Abstract: Background The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues. Methods Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable. Out of this data set, Cox regression with a stepwise selection method was recently published. Replication of methodical comparison (RSF and Cox regression) was conducted in two independent cohorts. Finally, the R-code for implementing the metabolite selection procedure into the RSF-syntax is provided. Results The application of the RSF approach in EPIC-Potsdam resulted in the identification of 16 incident T2D-associated metabolites which slightly improved prediction of T2D when used in addition to traditional T2D risk factors and also when used together with classical biomarkers. The identified metabolites partly agreed with previous findings using Cox regression, though RSF selected a higher number of highly correlated metabolites. Conclusions The RSF method appeared to be a promising approach for identification of disease-associated variables in complex data with time to event as outcome. The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data.
Harvard University1, German Cancer Research Center2, Brigham and Women's Hospital3, Aarhus University4, University of Paris-Sud5, University of Melbourne6, International Agency for Research on Cancer7, National and Kapodistrian University of Athens8, University of Ferrara9, Utrecht University10, University of Tromsø11, University of Murcia12, Umeå University13, Lund University14, Medical Research Council15, University of Cambridge16, Cancer Epidemiology Unit17, Imperial College London18
TL;DR: Evaluating the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study finds CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers.
Abstract: Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarker ...
International Agency for Research on Cancer1, Emory University2, Aarhus University3, French Institute of Health and Medical Research4, University of Paris5, German Cancer Research Center6, Academy of Athens7, National and Kapodistrian University of Athens8, University of Naples Federico II9, Utrecht University10, University of Granada11, Lund University12, Umeå University13, University of Cambridge14, University of Oxford15, Imperial College London16
TL;DR: In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
Abstract: Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
University of Cambridge1, Basque Government2, French Institute of Health and Medical Research3, Imperial College London4, Aarhus University5, Lund University6, German Cancer Research Center7, Cancer Epidemiology Unit8, University of Naples Federico II9, Aalborg University10, Prevention Institute11, Umeå University12, University of Turin13, University of Granada14, International Agency for Research on Cancer15, Utrecht University16, Wageningen University and Research Centre17
TL;DR: The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2d is more complex than the simple link suggested by the association of ferritin with T1D.
Abstract: OBJECTIVE Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors ...
Royal College of Surgeons in Ireland1, International Agency for Research on Cancer2, Charité3, National and Kapodistrian University of Athens4, Aarhus University5, French Institute of Health and Medical Research6, German Cancer Research Center7, Harvard University8, Prevention Institute9, University of Turin10, Imperial College London11, Utrecht University12, University of Tromsø13, University of Granada14, University of Murcia15, Umeå University16, University of Cambridge17, Cancer Epidemiology Unit18
TL;DR: Findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development.
TL;DR: Urinary excretion of 34 dietary polyphenols and their variations according to diet and other lifestyle factors were measured by tandem mass spectrometry in 475 adult participants from theEPIC cross-sectional study to allow more accurate evaluation of the relationships between polyphenol exposure and the risk of chronic diseases in large epidemiological studies.
Abstract: Urinary excretion of 34 dietary polyphenols and their variations according to diet and other lifestyle factors were measured by tandem mass spectrometry in 475 adult participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study. A single 24-hour urine sample was analysed for each subject from 4 European countries. The highest median levels were observed for phenolic acids such as 4-hydroxyphenylacetic acid (157 μmol/24 h), followed by 3-hydroxyphenylacetic, ferulic, vanillic and homovanillic acids (20–50 μmol/24 h). The lowest concentrations were observed for equol, apigenin and resveratrol ( 0.5) observed between urinary polyphenols and the intake of their main food sources (e.g., resveratrol and gallic acid ethyl ester with red wine intake; caffeic, protocatechuic and ferulic acids with coffee consumption; and hesperetin and naringenin with citrus fruit intake). The large variations in urinary polyphenols observed are largely determined by food preferences. These polyphenol biomarkers should allow more accurate evaluation of the relationships between polyphenol exposure and the risk of chronic diseases in large epidemiological studies.
Utrecht University1, Norfolk and Norwich University Hospital2, University of Cambridge3, Umeå University4, Lund University5, University of Oxford6, Aarhus University7, University of Paris-Sud8, University of Southern Denmark9, German Cancer Research Center10, National and Kapodistrian University of Athens11
TL;DR: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established and further studies are warranted to confirm this possible protective effect.
Abstract: BACKGROUND: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this rela ...
University of Oxford1, Utrecht University2, University of Cambridge3, Basque Government4, National and Kapodistrian University of Athens5, University of Rennes6, Lund University7, Institut Gustave Roussy8, German Cancer Research Center9, Imperial College London10, Prevention Institute11, University of Turin12, University of Granada13, University of Tromsø14, Aalborg University15, Aarhus University16, University of Naples Federico II17, Umeå University18, University of Gothenburg19
TL;DR: Having more children was associated with a higher risk of CHD later in life, whereas breastfeeding was associated for women who both had children and breastfed did have a non-significantly higher risk.
Abstract: Objective There is uncertainty about the direction and magnitude of the associations between parity, breastfeeding and the risk of coronary heart disease (CHD). We examined the separate and combined associations of parity and breastfeeding practices with the incidence of CHD later in life among women in a large, pan-European cohort study. Methods Data were used from European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD, a case-cohort study nested within the EPIC prospective study of 520,000 participants from 10 countries. Information on reproductive history was available for 14,917 women, including 5138 incident cases of CHD. Using Prentice-weighted Cox regression separately for each country followed by a random-effects meta-analysis, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD, after adjustment for age, study centre and several socioeconomic and biological risk factors. Results Compared with nulliparous women, the adjusted HR was 1.19 (95% CI: 1.01-1.41) among parous women; HRs were higher among women with more children (e.g., adjusted HR: 1.95 (95% CI: 1.19-3.20) for women with five or more children). Compared with women who did not breastfeed, the adjusted HR was 0.71 (95% CI: 0.52-0.98) among women who breastfed. For childbearing women who never breastfed, the adjusted HR was 1.58 (95% CI: 1.09-2.30) compared with nulliparous women, whereas for childbearing women who breastfed, the adjusted HR was 1.19 (95% CI: 0.99-1.43). Conclusion Having more children was associated with a higher risk of CHD later in life, whereas breastfeeding was associated with a lower CHD risk. Women who both had children and breastfed did have a non-significantly higher risk of CHD.
University of Gothenburg1, International Agency for Research on Cancer2, Université Paris-Saclay3, German Cancer Research Center4, National and Kapodistrian University of Athens5, Prevention Institute6, Centre for Health Protection7, University of Granada8, Lund University9, Umeå University10, University of Oxford11, Imperial College London12, University of Tromsø13
TL;DR: In this paper, the authors characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study, using cross-secti...
Abstract: OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.DESIGN: Cross-secti ...
Imperial College London1, Queen Mary University of London2, Utrecht University3, University of Cambridge4, University of London5, International Agency for Research on Cancer6, Umeå University7, German Cancer Research Center8, University of Oxford9, Andalusian School of Public Health10, Lund University11, National and Kapodistrian University of Athens12, Prevention Institute13, Institut Gustave Roussy14
TL;DR: The present study shows a slightly decreased—not increased like in case–control studies—risk of dying from ALS in those with high levels of total PA at enrolment, and this association does not appear confounded by age, gender, anthropometry, smoking, and education.
Abstract: Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33% less likely to die from ALS compared to those inactive: HR = 0.67 (95% CI 0.42-1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased-not increased like in case-control studies-risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity.
National Institutes of Health1, Mayo Clinic2, Utrecht University3, American Cancer Society4, University of Utah5, University of British Columbia6, City of Hope National Medical Center7, University of Freiburg8, Memorial Sloan Kettering Cancer Center9, Centre national de la recherche scientifique10, International Agency for Research on Cancer11, University of Alabama at Birmingham12, University of California, Berkeley13, Sorbonne14, Paris Descartes University15, Emory University16, Drexel University17, Fred Hutchinson Cancer Research Center18, Simon Fraser University19, University of Melbourne20, Cancer Council Victoria21, Statens Serum Institut22, Stanford University23, University of Texas MD Anderson Cancer Center24, Ohio State University25, University of York26, University of New South Wales27, Medical Research Council28, Harvard University29, University of Cagliari30, New York University31, Westat32, University of Iowa33, University of Rouen34, Paris 12 Val de Marne University35, University of Paris36, Uppsala University37, Karolinska Institutet38, Umeå University39, University of California, San Francisco40, University of Southern California41, Wayne State University42, University of North Carolina at Chapel Hill43, German Cancer Research Center44, University of Barcelona45, University of Burgundy46, Dublin City University47, Icahn School of Medicine at Mount Sinai48, Yale University49, Macquarie University50, National Institute for Health and Welfare51, Imperial College London52, University of Florence53, Dalian Maritime University54, University of Chicago55, Dongguk University56, Claude Bernard University Lyon 157
TL;DR: An analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls indicates that a genetic background that favors longer telomerre length may increase NHL risk, particularly risk of CLL/SLL, and is consistent with earlier studies relating longer telomeres length with increased NHL risk.
Abstract: Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
Utrecht University1, Imperial College London2, Aarhus University3, International Agency for Research on Cancer4, Institut Gustave Roussy5, French Institute of Health and Medical Research6, University of Melbourne7, German Cancer Research Center8, Academy of Athens9, National and Kapodistrian University of Athens10, Harvard University11, Prevention Institute12, University of Naples Federico II13, RMIT University14, University of Granada15, University of Gothenburg16, Umeå University17, University of Cambridge18, Cancer Epidemiology Unit19
TL;DR: Evidence is provided that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk and the test for heterogeneity by hormone receptor status was not significant.
International Agency for Research on Cancer1, Imperial College London2, University of Ioannina3, Institut Gustave Roussy4, French Institute of Health and Medical Research5, University of Paris-Sud6, German Cancer Research Center7, Aarhus University8, University of Granada9, University of Murcia10, University of Cambridge11, University of Oxford12, National and Kapodistrian University of Athens13, Prevention Institute14, University of Naples Federico II15, Utrecht University16, Lund University17, Malmö University18, Umeå University19, University of Tromsø20
TL;DR: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially.
Abstract: This work was supported by the French Social Affairs & Health Ministry, Department of Health (Direction Generale de la Sante). The work undertaken by David C Muller for this project was performed during the tenure of an IARC-Australia fellowship supported by Cancer Council Australia. Elio Riboli was supported by the Imperial College Biomedical Research Centre funded by the National Institute of Health Research of UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l’Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom).
TL;DR: Omentin-1 concentrations may be related to increased stroke risk, and this association is stronger in metabolically healthy individuals.
TL;DR: Investigating serum concentrations of IGF-1 and IGFBP-3 and their molar ratio in relation to T2DM incidence in a nested case-cohort study within the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study does not confirm an association between total IGF- 1 concentrations and risk of T2 DM in the general study population, although higher IGF BP-3 levels might raise T 2DM risk independent of IGF -1 levels.
Abstract: Higher levels of insulin-like growth factor-binding protein 3 (IGFBP-3) might raise the risk of type 2 diabetes mellitus (T2DM) via binding of insulin-like growth factor 1 (IGF-1), an insulin-like hormone that is involved in glucose homeostasis. We investigated serum concentrations of IGF-1 and IGFBP-3 and their molar ratio in relation to T2DM incidence in a nested case-cohort study within the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study. We included a randomly selected subcohort of persons without T2DM at the time of blood sampling (n = 2,269) and 776 individuals with incident T2DM identified between 1994 and 2005. For the highest quartile versus lowest, the multivariable-adjusted hazard rate ratios were 0.91 (95% confidence interval (CI): 0.68, 1.23; P for trend = 0.31) for IGF-1, 1.33 (95% CI: 1.00, 1.76; P for trend = 0.04) for IGFBP-3, and 0.77 (95% CI: 0.57, 1.03; P for trend = 0.03) for IGF-1:IGFBP-3 ratio. IGFBP-3 level remained positively associated with T2DM incidence-and the ratio of IGF-1 to IGFBP-3 was inversely related with T2DM incidence--in models that included adjustment for IGF-1 concentrations (P for trend < 0.05). Therefore, our findings do not confirm an association between total IGF-1 concentrations and risk of T2DM in the general study population, although higher IGFBP-3 levels might raise T2DM risk independent of IGF-1 levels.