| 21. |
- Langenberg, Claudia, et al.
(författare)
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Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study.
- 2014
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.
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| 22. |
- Li, Sherly X, et al.
(författare)
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Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:6, s. 1325-1332
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Tidskriftsartikel (refereegranskat)abstract
- Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution.No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined.Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.
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| 23. |
- Lotta, Luca A., et al.
(författare)
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Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:1, s. 17-26
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.
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| 24. |
- Merritt, Melissa A., et al.
(författare)
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Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study
- 2016
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:1, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.
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| 25. |
- Merritt, Melissa A, et al.
(författare)
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Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition : a cohort study
- 2015
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled > 500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (>= 15 years versus < 12; 0.90; 0.85-0.96; P for trend = 0.038). Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.
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| 26. |
- Purdue, Mark P, et al.
(författare)
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Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:1, s. 60-65
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
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| 27. |
- Ricci, Cristian, et al.
(författare)
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Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke : EPIC-CVD case-cohort study
- 2018
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Ingår i: The BMJ. - : BMJ PUBLISHING GROUP. - 1756-1833 .- 0959-8138. ; 361
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN Multicentre case-cohort study. SETTING A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/ day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
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| 28. |
- van Woudenbergh, Geertruida J., et al.
(författare)
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Tea Consumption and Incidence of Type 2 Diabetes in Europe : The EPIC-InterAct Case-Cohort Study
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e36910-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population. Methodology/Principal Findings: The EPIC-InterAct case-cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country-specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0-<1, 1-<4, >= 4 cups/day). The dose-response of the association was further explored by restricted cubic spline regression. Country specific medians of tea consumption ranged from 0 cups/day in Spain to 4 cups/day in United Kingdom. Tea consumption was associated inversely with incidence of type 2 diabetes; the HR was 0.84 [95% CI 0.71, 1.00] when participants who drank >= 4 cups of tea per day were compared with non-drinkers (p(linear) (trend) = 0.04). Incidence of type 2 diabetes already tended to be lower with tea consumption of 1-<4 cups/day (HR = 0.93 [95% CI 0.81, 1.05]). Spline regression did not suggest a non-linear association (p(non-linearity) = 0.20). Conclusions/Significance: A linear inverse association was observed between tea consumption and incidence of type 2 diabetes. People who drink at least 4 cups of tea per day may have a 16% lower risk of developing type 2 diabetes than non-tea drinkers.
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| 29. |
- Zamora-Ros, Raul, et al.
(författare)
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The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations The EPIC-InterAct study
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 36:12, s. 3961-3970
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVETo study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.RESEARCH DESIGN AND METHODSThe European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.RESULTSIn multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes.CONCLUSIONSProspective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.
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| 30. |
- Aglago, Elom K., et al.
(författare)
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Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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