| 1. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 2. |
- Zamora-Ros, R., et al.
(författare)
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Impact of thearubigins on the estimation of total dietary flavonoids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 67:7, s. 779-782
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Tidskriftsartikel (refereegranskat)abstract
- Thearubigins (TR) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves. Comprising similar to 70% of total polyphenols in black tea, TR may contribute majorly to its beneficial effects on health. To date, there is no appropriate food composition data on TR, although several studies have used data from the US Department of Agriculture (USDA) database to estimate TR intakes. We aimed to estimate dietary TR in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and assess the impact of including TR or not in the calculation of the total dietary flavonoid intake. Dietary data were collected using a single standardized 24-h dietary recall interviewer-administered to 36 037 subjects aged 35-74 years. TR intakes were calculated using the USDA database. TR intakes ranged from 0.9 mg/day in men from Navarra and San Sebastian in Spain to 532.5 mg/day in men from UK general population. TR contributed <5% to the total flavonoid intake in Greece, Spain and Italy, whereas in the UK general population, TR comprised 48% of the total flavonoids. High heterogeneity in TR intake across the EPIC countries was observed. This study shows that total flavonoid intake may be greatly influenced by TR, particularly in high black tea-consuming countries. Further research on identification and quantification of TR is needed to get more accurate dietary TR estimations.
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| 3. |
- Bendinelli, B., et al.
(författare)
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Association between dietary meat consumption and incident type 2 diabetes : the EPIC-InterAct study
- 2013
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 56:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption.Results: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants.Conclusions/interpretation: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.
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| 4. |
- Duell, E. J., et al.
(författare)
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Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:9, s. 2164-2175
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Tidskriftsartikel (refereegranskat)abstract
- Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.99-2.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort. What's new Because the incidence of pancreatic cancer is 30-50% higher in men than women, researchers have wondered whether exposure to estrogen might offer a protective effect. The answer thus far has been unclear, however. In this study, the authors examined menstrual and reproductive factors in women, as well as exogenous hormone use. They also examined variants of the CYP17A1 gene in both women and men, as this gene is essential for sex-steroid metabolism. Only early age of menarche showed any association with pancreatic cancer risk. Copyright © 2012 UICC.
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| 5. |
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| 6. |
- Ekelund, U., et al.
(författare)
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Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women : the EPIC-InterAct Study
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:7, s. 1944-1952
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Tidskriftsartikel (refereegranskat)abstract
- We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.
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| 7. |
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| 8. |
- Heath, A. K., et al.
(författare)
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Nutrient-wide association study of 92 foods and nutrients and breast cancer risk
- 2020
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
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| 9. |
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| 10. |
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| 11. |
- Rohrmann, S., et al.
(författare)
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The association of education with long-term weight change in the EPIC-PANACEA cohort
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 957-963
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: EPIC is a cohort study with 361 467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time. RESULTS: Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and -70 g per year (95% CI -90; -60), respectively). CONCLUSIONS: Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Zamora-Ros, R., et al.
(författare)
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Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 932-941
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36 037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.
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| 16. |
- Assi, N., et al.
(författare)
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A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2016
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Ingår i: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 19:2, s. 242-254
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Tidskriftsartikel (refereegranskat)abstract
- Copyright © The Authors 2015 Objective: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Design: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. Setting: The European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects: Women (n 334 850) from the EPIC study. Results: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01). Conclusions: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.
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| 17. |
- Buijsse, B, et al.
(författare)
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Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.
- 2015
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 69:4, s. 455-461
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives:Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D.Subjects/Methods:A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12 403 incident T2D cases and a subcohort of 16 835 people, identified from a cohort of 340 234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis.Results:After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D.Conclusions:Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.European Journal of Clinical Nutrition advance online publication, 26 November 2014; doi:10.1038/ejcn.2014.249.
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| 18. |
- Cordova, R., et al.
(författare)
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Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Berlin/Heidelberg. - 1436-6207 .- 1436-6215. ; 59, s. 2893-2904
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up.Methods: A total of 255,170 participants aged 25–70 years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects.Results: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087–0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041–0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish.Conclusion: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.
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| 19. |
- Matejcic, M., et al.
(författare)
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Biomarkers of folate and vitamin B12 and breast cancer risk : report from the EPIC cohort
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:6, s. 1246-1259
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1=1.26; 95% CI 1.00-1.58; P-trend=0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1=1.29; 95% CI 1.02-162; P-trend=0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
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| 20. |
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| 21. |
- Raaschou-Nielsen, O., et al.
(författare)
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Particulate matter air pollution components and risk for lung cancer
- 2016
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 87, s. 66-73
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Tidskriftsartikel (refereegranskat)abstract
- Background: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. Methods: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. Results: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 125; 95% Cl, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m3), PMio S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PMio and PM2.5 and lung cancer were largely explained by PM2.5 S. Conclusions: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.
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| 22. |
- Rohrmann, S., et al.
(författare)
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Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:3, s. 708-714
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
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| 23. |
- Salvi, Erika, et al.
(författare)
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Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase.
- 2012
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Ingår i: Hypertension. - 1524-4563. ; 59:2, s. 248-248
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Tidskriftsartikel (refereegranskat)abstract
- Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.
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| 24. |
- Schumann, Gunter, et al.
(författare)
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Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:17, s. 7119-7124
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of similar to 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Downregulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
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| 25. |
- Botteri, Edoardo, et al.
(författare)
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Lifestyle changes in middle age and risk of cancer : evidence from the European Prospective Investigation into Cancer and Nutrition
- 2024
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Ingår i: European Journal of Epidemiology. - 0393-2990. ; 39:2, s. 147-159
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.
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