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1.	Lu, Yingchang, et al. (författare) A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk. 2018 Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430 Tidskriftsartikel (refereegranskat)abstract .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
2.	Naska, A, et al. (författare) Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study. 2011 Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 35:3, s. 416-426 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. SUBJECTS: This study included a representative sample of 24,310 randomly selected EPIC participants. METHODS: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders. RESULTS: In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (β=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (β=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake. CONCLUSION: Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.
3.	Gonzalez, C. A., et al. (författare) Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project 2012 Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:5, s. 1320-1324 Tidskriftsartikel (refereegranskat)abstract In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII((R))). By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.
4.	Molina-Montes, E., et al. (författare) Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort 2012 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:7 Tidskriftsartikel (refereegranskat)abstract Several studies support a protective effect of dietary magnesium against type 2 diabetes, but a harmful effect for iron. As diabetes has been linked to pancreatic cancer, intake of these nutrients may be also associated with this cancer. We examined the association between dietary intake of magnesium, total iron and heme-iron and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In total, 142,203 men and 334,999 women, recruited between 1992 and 2000, were included. After an average follow-up of 11.3 years, 396 men and 469 women developed exocrine pancreatic cancer. Hazard ratios and 95% confidence intervals (CIs) were obtained using Cox regression stratified by age and center, and adjusted for energy intake, smoking status, height, weight, and self-reported diabetes status. Neither intake of magnesium, total iron nor heme-iron was associated with pancreatic cancer risk. In stratified analyses, a borderline inverse association was observed among overweight men (body mass index, =25 kg/m2) with magnesium (HRper 100 mg/day increase = 0.79, 95% CI = 0.631.01) although this was less apparent using calibrated intake. In female smokers, a higher intake of heme-iron was associated with a higher pancreatic cancer risk (HR per 1 mg/day increase = 1.38, 95% CI = 1.101.74). After calibration, this risk increased significantly to 2.5-fold (95% CI = 1.225.28). Overall, dietary magnesium, total iron and heme-iron were not associated with pancreatic cancer risk during the follow-up period. Our observation that heme-iron was associated with increased pancreatic cancer risk in female smokers warrants replication in additional study populations.
5.	Dossus, L, et al. (författare) Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort 2014 Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 134:8, s. 1871-1888 Tidskriftsartikel (refereegranskat)
6.	Langenberg, C., et al. (författare) Design and cohort description of the InterAct Project : an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study 2011 Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 54:9, s. 2272-2282 Tidskriftsartikel (refereegranskat)abstract Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.
7.	Rohrmann, S., et al. (författare) The association of education with long-term weight change in the EPIC-PANACEA cohort 2012 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 957-963 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.
8.	Fortner, RT, et al. (författare) Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort 2017 Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:1, s. 26- Tidskriftsartikel (refereegranskat)
9.	Roura, E, et al. (författare) Correction: The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort 2016 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3, s. e0151427- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
10.	Buckland, G., et al. (författare) Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study 2014 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:10, s. 2504-2511 Tidskriftsartikel (refereegranskat)abstract There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. What's new? Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire-based associations between dietary factors and bladder cancer risk.
11.	Idahl, Annika, 1965-, et al. (författare) Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk : results from the EPIC cohort 2019 Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29, s. A473-A474 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Introduction/Background Sexually transmitted infections (STI) and pelvic inflammatory disease may cause damage to the fallopian tube where a substantial proportion of epithelial ovarian cancer (EOC) likely arises. The aim of this study was to determine whether Chlamydia trachomatis antibodies are associated with higher EOC risk. As secondary objectives, we investigated Mycoplasma genitalium,herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 and EOC risk.Methodology In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort,791 cases and 1,669 matched controls with pre-diagnosis blood samples were analyzed. Cases and controls were matched on study center, and at blood collection age, time of day, fasting status, exogenous hormone use, menopausal status, and menstrual cycle phase. Antibodies against C. trachomatis, M. genitalium, HSV-2, and HPV 16, 18 and 45 (E6, E7, L1) were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals [CI] comparing women with positive vs. negative serology.Results A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but was associated with higher risk of the mucinous histotype (RR=2.56 [95% CI=1.3–5.05]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1), produced during persistent infection, was associated with higher risk of EOC overall (1.33 [1.09–1.62]) and of the serous subtype (1.42 [1.09–1.84]). None of the other evaluated STIs were associated with EOC risk overall; in analyses by histotype, HSV-2 was associated with higher risk of endometrioid EOC (2.93 [1.50–5.74]).Conclusion C. trachomatis infection may influence carcinogenesis of serous and mucinous EOC, while HSV-2 might promote endometrioid disease. Mechanisms linking STIs to EOC need to be further elucidated.
12.	Li, K., et al. (författare) An epidemiologic risk prediction model for ovarian cancer in Europe : the EPIC study 2015 Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:7, s. 1257-1265 Tidskriftsartikel (refereegranskat)abstract Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. Conclusion: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.
13.	Navarrete-Munoz, EM, et al. (författare) Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) 2016 Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 104:3, s. 760-768 Tidskriftsartikel (refereegranskat)
14.	Noethlings, U., et al. (författare) Food intake of individuals with and without diabetes across different countries and ethnic groups 2011 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 65:5, s. 635-641 Tidskriftsartikel (refereegranskat)abstract Background/Objectives: Given the importance of nutrition therapy in diabetes management, we hypothesized that food intake differs between individuals with and without diabetes. We investigated this hypothesis in two large prospective studies including different countries and ethnic groups. Subjects/Methods: Study populations were the European Prospective Investigation into Cancer and Nutrition Study (EPIC) and the Multiethnic Cohort Study (MEC). Dietary intake was assessed by food frequency questionnaires, and calibrated using 24h-recall information for the EPIC Study. Only confirmed self-reports of diabetes at cohort entry were included: 6192 diabetes patients in EPIC and 13 776 in the MEC. For the cross-sectional comparison of food intake and lifestyle variables at baseline, individuals with and without diabetes were matched 1: 1 on sex, age in 5-year categories, body mass index in 2.5 kg/m(2) categories and country. Results: Higher intake of soft drinks (by 13 and 44% in the EPIC and MEC), and lower consumption of sweets, juice, wine and beer (> 10% difference) were observed in participants with diabetes compared with those without. Consumption of vegetables, fish and meat was slightly higher in individuals with diabetes in both studies, but the differences were <10%. Findings were more consistent across different ethnic groups than countries, but generally showed largely similar patterns. Conclusions: Although diabetes patients are expected to undergo nutritional education, we found only small differences in dietary behavior in comparison with cohort members without diabetes. These findings suggest that emphasis on education is needed to improve the current behaviors to assist in the prevention of complications. European Journal of Clinical Nutrition (2011) 65, 635-641; doi: 10.1038/ejcn.2011.11; published online 23 February 2011
15.	Obon-Santacana, M., et al. (författare) Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort 2013 Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:10, s. 2645-2651 Tidskriftsartikel (refereegranskat)abstract In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures. A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes > 500 000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously. After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 mu g/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 mu g/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 mu g/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, >= 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio. Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.
16.	Zamora-Ros, R., et al. (författare) Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study 2014 Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:9, s. 1870-1880 Tidskriftsartikel (refereegranskat)abstract Background: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. Results: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n = 430) and non-aggressive (n = 413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend = 0.009) and lignans (HRQ5-Q 10.78, 95% CI: 0.62-0.96; P-trend = 0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. Conclusions: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.
17.	Bendinelli, B., et al. (författare) Association between dietary meat consumption and incident type 2 diabetes : the EPIC-InterAct study 2013 Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 56:1, s. 47-59 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.
18.	Cust, A. E., et al. (författare) Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition 2009 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 37-60 Tidskriftsartikel (refereegranskat)abstract Objective: To describe dietary carbohydrate intakes and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36 034 subjects, aged between 35-74 years, were administered a standardized, 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total carbohydrate, sugars, starch and fibre were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. Results: Adjusted mean total carbohydrate intakes were highest in Italy and in the UK health-conscious cohort, and were lowest in Spain, Greece and France. Total fibre intakes were highest in the UK health-conscious cohort and lowest in Sweden and the UK general population. Bread contributed the highest proportion of carbohydrates (mainly starches) in every centre. Fruit consumption contributed a greater proportion of total carbohydrates (mainly sugars) among women than among men, and in southern centres compared with northern centres. Bread, fruits and vegetables represented the largest sources of fibre, but food sources varied considerably between centres. In stratified analyses, carbohydrate intakes tended to be higher among subjects who were physically active, never-smokers or non-drinkers of alcohol. Conclusions: Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease. European Journal of Clinical Nutrition (2009) 63, S37-S60; doi: 10.1038/ejcn.2009.74
19.	Nagel, G., et al. (författare) Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) 2010 Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 119:3, s. 753-765 Tidskriftsartikel (refereegranskat)abstract So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.
20.	Rohrmann, S., et al. (författare) Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition 2012 Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106, s. 1004-1010 Tidskriftsartikel (refereegranskat)abstract Background: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.Methods:Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables.Results:Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (O=R1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction0.154). Conclusion: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk. © 2012 Cancer Research UK All rights reserved.
21.	Schlesinger, S, et al. (författare) Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort 2013 Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:9, s. 2449-2455 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.
22.	Sund, Malin, et al. (författare) Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: A nested case-control study Plasma micronutrients and pancreatic cancer risk 2015 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:6 Tidskriftsartikel (refereegranskat)abstract Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (- and -carotene, lycopene, -cryptoxanthin, canthaxanthin, zeaxanthin and lutein), - and -tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma -carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend=0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend=0.06) and -tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend=0.08. For - and -carotene, lutein, sum of carotenoids and -tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of -carotene, zeaxanthin and -tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted. What's new? Fruits and vegetables may play a role in the prevention of pancreatic cancer, but associations between the antioxidants those foods contain and disease risk remain unclear. In this study, pancreatic cancer risk was inversely associated with increased prediagnostic plasma concentrations of the antioxidants -carotene, zeaxanthin, and -tocopherol. Geographic variations were also detected. In Northern European countries, inverse associations with risk were found for blood levels of several carotenoids, whereas the association was strongest for -tocopherol in Southern European countries. The role of carotenoids and vitamins should be considered in subsequent investigations of the etiology of pancreatic cancer.
23.	Abbas, S., et al. (författare) Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study 2014 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 68:2, s. 196-202 Tidskriftsartikel (refereegranskat)abstract BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires. RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D. CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.
24.	Campmans-Kuijpers, M.J.E., et al. (författare) Isocaloric substitution of carbohydrates with protein: The association with weight change and mortality among patients with type 2 diabetes 2015 Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 14 Tidskriftsartikel (refereegranskat)abstract © 2015 Campmans-Kuijpers et al.; licensee BioMed Central. Background: The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes. Methods: The study included 6,107 diabetes patients from 15 European cohorts. Patients with type 1 diabetes were excluded. At recruitment, validated country-specific food-frequency questionnaires were used to estimate dietary intake. Multivariable adjusted linear regression was used to examine the associations between dietary carbohydrate substitution with protein and 5-year weight change, and Cox regression to estimate hazard ratios (HRs) for (CVD) mortality. Results: Annual weight loss of patients with type 2 diabetes was 0.17 (SD 1.24) kg. After a mean follow-up of 9.2 (SD 2.3)y, 787 (13%) participants had died, of which 266 (4%) deaths were due to CVD. Substitution of 10 gram dietary carbohydrate with total (ß = 187 [75;299]g) and animal (ß = 196 [137;254]g) protein was associated with mean 5-year weight gain. Substitution for plant protein was not significantly associated with weight change (β = 82 [-421;584]g). Substitution with plant protein was associated with lower all-cause mortality risk (HR = 0.79 [0.64;0.97]), whereas substitution with total or animal protein was not associated with (CVD) mortality risk. Conclusions: In diabetes patients, substitution with plant protein was beneficial with respect to weight change and all-cause mortality as opposed to substitution with animal protein. Therefore, future research is needed whether dietary guidelines should not actively promote substitution of carbohydrates by total protein, but rather focus on substitution of carbohydrates with plant protein.
25.	Jakszyn, Paula, et al. (författare) Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European prospective investigation into cancer and nutrition (EPIC) 2011 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:3, s. 555-559 Tidskriftsartikel (refereegranskat)abstract Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 20(3); 555-9. ©2011 AACR.
26.	Orfanos, P., et al. (författare) Eating at restaurants, at work or at home. Is there a difference? : a study among adults of 11 European countries in the context of the HECTOR* project 2017 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 71:3, s. 407-419 Tidskriftsartikel (refereegranskat)abstract BACKGROUND/OBJECTIVES: To compare macronutrient intakes out of home-by location-to those at home and to investigate differences in total daily intakes between individuals consuming more than half of their daily energy out of home and those eating only at home.SUBJECTS/METHODS: Data collected through 24-h recalls or diaries among 23 766 European adults. Participants were grouped as 'non-substantial', 'intermediate' and 'very substantial out-of-home' eaters based on energy intake out of home. Mean macronutrient intakes were estimated at home and out of home (overall, at restaurants, at work). Study/cohort-specific mean differences in total intakes between the 'very substantial out-of-home' and the 'at-home' eaters were estimated through linear regression and pooled estimates were derived.RESULTS: At restaurants, men consumed 29% of their energy as fat, 15% as protein, 45% as carbohydrates and 11% as alcohol. Among women, fat contributed 33% of energy intake at restaurants, protein 16%, carbohydrates 45% and alcohol 6%. When eating at work, both sexes reported 30% of energy from fat and 55% from carbohydrates. Intakes at home were higher in fat and lower in carbohydrates and alcohol. Total daily intakes of the 'very substantial out-of-home' eaters were generally similar to those of individuals eating only at home, apart from lower carbohydrate and higher alcohol intakes among individuals eating at restaurants.CONCLUSIONS: In a large population of adults from 11 European countries, eating at work was generally similar to eating at home. Alcoholic drinks were the primary contributors of higher daily energy intakes among individuals eating substantially at restaurants.
27.	Sarink, D, et al. (författare) Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort 2017 Ingår i: Cancer prevention research (Philadelphia, Pa.). - 1940-6215. ; 10:9, s. 525-534 Tidskriftsartikel (refereegranskat)
28.	Allen, NE, et al. (författare) Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition 2007 Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 16:6, s. 1121-1127 Tidskriftsartikel (refereegranskat)
29.	Brand, J. S., et al. (författare) Diabetes and onset of natural menopause : results from the European Prospective Investigation into Cancer and Nutrition 2015 Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 30:6, s. 1491-1498 Tidskriftsartikel (refereegranskat)abstract STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.
30.	Brand, J. S., et al. (författare) Diabetes and Onset of Natural Menopause : Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT 2015 Ingår i: Obstetrical and Gynecological Survey. - 0029-7828 .- 1533-9866. ; 70:8, s. 507-508 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and <10 years [HR, 1.59; 95% CI, 1.03-2.43]), whereas women with diabetes at age 50 years or older had a later menopause (HR, 0.81; 95% CI, 0.70-0.95). No association with ANM was found for diabetes onset between the ages 20 and 50 years. Strengths of the study include its large sample size and the measurement of a broad set of potential confounders. However, there were several limitations. First, results may have been underestimated because of survival bias. Second, the sequence of menopause and diabetes in women with a late age at diabetes is uncertain, as both events occur in a short period, and both diabetes and menopause status were based on self-report, not verified by medical records. Third, no distinction was made between types 1 and 2 diabetes. Although there is no overall association between diabetes and age at menopause, the data suggest that early-onset diabetes may accelerate menopause. The delaying effect of late-onset diabetes on ANM is not in agreement with other studies suggesting the opposite association.
31.	Elks, Cathy E., et al. (författare) Age at Menarche and Type 2 Diabetes Risk The EPIC-InterAct study 2013 Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 36:11, s. 3526-3534 Tidskriftsartikel (refereegranskat)abstract OBJECTIVEYounger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.RESEARCH DESIGN AND METHODSThe prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.RESULTSMean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m(2) lower adult BMI. Women in the earliest menarche quintile (8-11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49-1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18-1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.CONCLUSIONSWomen with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
32.	Linseisen, J., et al. (författare) Dietary fat intake in the European Prospective Investigation into Cancer and Nutrition: results from the 24-h dietary recalls 2009 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 61-80 Tidskriftsartikel (refereegranskat)abstract Objectives: This paper describes the dietary intake of total fat, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) and cholesterol of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) in 27 centres across 10 countries. Methods: Between 1995 and 2000, a stratified random sample of 36 034 participants (age range 35-74 years) completed a standardized 24-h dietary recall, assessed by means of the computer software EPIC-SOFT. Lipid intake data were calculated using a standardized nutrient database. Results: On average, the contribution of fat to total energy intake was >= 34% of energy intake (% en) in women and >= 36% en in men for most EPIC centres, except for the British, Dutch and most Italian cohorts. Total fat (> 40% en) and MUFA intakes (21% en, mainly from olive oil) were highest in Greece. Except for the Greek, Spanish and Italian centres, the average MUFA intake ranged between 10 and 13% en, with a high proportion derived from animal sources. SFA intake in women and men was lowest in the Greek, Spanish, Italian and UK cohorts with an average of <= 13% en (down to 9% en), and highest in the Swedish centres (16% en). The mean PUFA intake was in the range of 4-8% en, being highest in the UK health-conscious cohort. The average cholesterol intake across EPIC varied from 140 to 384 mg/d in women and 215-583 mg/d in men. Conclusions: The presented data show differences and similarities in lipid intake across the European EPIC cohorts and also show differences in food sources of dietary lipids. European Journal of Clinical Nutrition (2009) 63, S61-S80; doi: 10.1038/ejcn.2009.75
33.	Ekelund, Ulf, et al. (författare) Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women. 2011 Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 93, s. 826-835 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The protective effect of physical activity (PA) on abdominal adiposity is unclear. OBJECTIVE: We examined whether PA independently predicted gains in body weight and abdominal adiposity. DESIGN: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable). RESULTS: PA significantly predicted a lower waist circumference (in cm) in men (β = -0.045; 95% CI: -0.057, -0.034) and in women (β = -0.035; 95% CI: -0.056, -0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (β = -0.008; 95% CI: -0.02, 0.003) and women (β = -0.01; 95% CI: -0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively. CONCLUSION: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.
34.	Freisling, Heinz, et al. (författare) Dietary acrylamide intake of adults in the European Prospective Investigation into Cancer and Nutrition differs greatly according to geographical region 2013 Ingår i: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 52:4, s. 1369-1380 Tidskriftsartikel (refereegranskat)abstract Methodological differences in assessing dietary acrylamide (AA) often hamper comparisons of intake across populations. Our aim was to describe the mean dietary AA intake in 27 centers of 10 European countries according to selected lifestyle characteristics and its contributing food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In this cross-sectional analysis, 36 994 men and women, aged 35-74 years completed a single, standardized 24-hour dietary recall using EPIC-Soft. Food consumption data were matched to a harmonized AA database. Intake was computed by gender and center, and across categories of habitual alcohol consumption, smoking status, physical activity, education, and body mass index (BMI). Adjustment was made for participants' age, height, weight, and energy intake using linear regression models. Adjusted mean AA intake across centers ranged from 13 to 47 mu g/day in men and from 12 to 39 mu g/day in women; intakes were higher in northern European centers. In most centers, intake in women was significantly higher among alcohol drinkers compared with abstainers. There were no associations between AA intake and physical activity, BMI, or education. At least 50 % of AA intake across centers came from two food groups "bread, crisp bread, rusks" and "coffee." The third main contributing food group was "potatoes". Dietary AA intake differs greatly among European adults residing in different geographical regions. This observed heterogeneity in AA intake deserves consideration in the design and interpretation of population-based studies of dietary AA intake and health outcomes.
35.	Gallo, Valentina, et al. (författare) Exploring causality of the association between smoking and Parkinson's disease 2019 Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 48:3, s. 912-925 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.
36.	Gallo, Valentina, et al. (författare) Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study 2016 Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 31:3, s. 255-266 Tidskriftsartikel (refereegranskat)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 through 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.
37.	Jakobsen, Marianne U., et al. (författare) Plasma Phospholipid Long-Chain n-3 Polyunsaturated Fatty Acids and Body Weight Change 2011 Ingår i: Obesity Facts. - : S. Karger AG. - 1662-4033 .- 1662-4025. ; 4:4, s. 312-318 Tidskriftsartikel (refereegranskat)abstract Objective: We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. Method: A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. Results: The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. Conclusion: The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.
38.	Kroeger, J., et al. (författare) Specific food group combinations explaining the variation in intakes of nutrients and other important food components in the European Prospective Investigation into Cancer and Nutrition: an application of the reduced rank regression method 2009 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 263-274 Tidskriftsartikel (refereegranskat)abstract Objective: To identify combinations of food groups that explain as much variation in absolute intakes of 23 key nutrients and food components as possible within the country-specific populations of the European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects/Methods: The analysis covered single 24-h dietary recalls (24-HDR) from 36 034 subjects (13 025 men and 23 009 women), aged 35-74 years, from all 10 countries participating in the EPIC study. In a set of 39 food groups, reduced rank regression (RRR) was used to identify those combinations (RRR factors) that explain the largest proportion of variation in intake of 23 key nutrients and food components, namely, proteins, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, sugars (sum of mono-and disaccharides), starch, fibre, alcohol, calcium, iron, potassium, phosphorus, magnesium, vitamin D, beta-carotene, retinol and vitamins E, B1, B2, B6, B12 and C (RRR responses). Analyses were performed at the country level and for all countries combined. Results: In the country-specific analyses, the first RRR factor explained a considerable proportion of the total nutrient intake variation in all 10 countries (27.4-37.1%). The subsequent RRR factors were much less important in explaining the variation (<= 6%). Strong similarities were observed for the first country-specific RRR factor between the individual countries, largely characterized by consumption of bread, vegetable oils, red meat, milk, cheese, potatoes, margarine and processed meat. The highest explained variation was seen for protein, potassium, phosphorus and magnesium (50-70%), whereas sugars, beta-carotene, retinol and alcohol were only marginally explained (<= 5%). The explained proportion of the other nutrients ranged between these extremes. Conclusions: A combination of food groups was identified that explained a considerable proportion of the nutrient intake variation in 24-HDRs in every country-specific EPIC population in a similar manner. This indicates that, despite the large variability in food and nutrient intakes reported in the EPIC, the variance of intake of important nutrients is explained, to a large extent, by similar food group combinations across countries. European Journal of Clinical Nutrition (2009) 63, S263-S274; doi: 10.1038/ejcn.2009.85
39.	Langenberg, Claudia, et al. (författare) Long-Term Risk of Incident Type 2 Diabetes and Measures of Overall and Regional Obesity: The EPIC-InterAct Case-Cohort Study 2012 Ingår i: PLoS Medicine. - San Francisco : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 9:6 Tidskriftsartikel (refereegranskat)abstract Background: Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI). Methods and Findings: The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (< 94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI >= 35 kg/m(2)) and a high WC (> 102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women). Conclusions: WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.
40.	May, Anne M., et al. (författare) Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study 2012 Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 12 Tidskriftsartikel (refereegranskat)abstract Background: This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. Methods: Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. Results: Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially >= 30 kg/m2, 1.26 (1.23; 1.29)). Conclusions: Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.
41.	Merritt, Melissa A., et al. (författare) 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 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:1, s. 161-167 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.
42.	Podmore, Clara, et al. (författare) Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes : The EPIC-InterAct Study 2016 Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:4, s. 572-581 Tidskriftsartikel (refereegranskat)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 other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D.RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition-InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population.RESULTS Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100mg/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and g-glutamyl transferase. Elevated TSAT (>= 45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (P-interaction < 0.01).CONCLUSIONS 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 T2D.
43.	Ros, Martine M., et al. (författare) Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition 2012 Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:17, s. 3267-3277 Tidskriftsartikel (refereegranskat)abstract Background: Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After 8.9 years of follow-up, 947 UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Results: Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78-1.00 and HR 0.87; 95% CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95% CI 0.77-0.98). Conclusion: Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded. (C) 2012 Elsevier Ltd. All rights reserved.
44.	Roswall, Nina, et al. (författare) Consumption of predefined 'Nordic' dietary items in ten European countries : an investigation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort 2014 Ingår i: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 17:12, s. 2650-2659 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Health-beneficial effects of adhering to a healthy Nordic diet index have been suggested. However, it has not been examined to what extent the included dietary components are exclusively related to the Nordic countries or if they are part of other European diets as well, suggesting a broader preventive potential. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe. DESIGN: Cross-sectional study. A 24 h dietary recall was administered through a software program containing country-specific recipes. Sex-specific mean food intake was calculated for each centre/country, as well as percentage of overall food groups consumed as healthy Nordic food items. All analyses were weighted by day and season of data collection. SETTING: Multi-centre, European study. SUBJECTS: Persons (n 36 970) aged 35-74 years, constituting a random sample of 519 978 EPIC participants. RESULTS: The highest intakes of the included diet components were: cabbages and berries in Central Europe; apples/pears in Southern Europe; dark bread in Norway, Denmark and Greece; fish in Southern and Northern countries; shellfish in Spain; and root vegetables in Northern and Central Europe. Large inter-centre variation, however, existed in some countries. CONCLUSIONS: Dark bread, root vegetables and fish are strongly related to a Nordic dietary tradition. Apples/pears, berries, cabbages, fish, shellfish and root vegetables are broadly consumed in Europe, and may thus be included in regional public health campaigns.
45.	Sieri, Sabina, et al. (författare) Glycemic index, glycemic load, and risk of coronary heart disease : a pan-European cohort study 2020 Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 112:3, s. 631-643 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. OBJECTIVES: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. METHODS: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. RESULTS: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. CONCLUSIONS: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.
46.	Steffen, Annika, et al. (författare) Anthropometry and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition 2009 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 18:7, s. 2079-2089 Tidskriftsartikel (refereegranskat)abstract Background: Increasing evidence suggests that general obesity [measured by body mass index (BMI)] is positively associated with risk of esophageal adenocarcinoma (EAC). In contrast, previous studies have shown inverse relations with esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether body fat distribution, particularly abdominal obesity, is associated with each type of esophageal cancer. Methods: We applied multivariable adjusted Cox proportional hazards regression to investigate the association between anthropometric measures and risk of EAC and ESCC among 346,554 men and women participating in the European Prospective Investigation into Cancer and Nutrition. All statistical tests were two sided. Results: During 8.9 years of follow-up, we documented 88 incident cases of EAC and 110 cases of ESCC. BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with EAC risk [highest versus lowest quintile; relative risk (RR), 2.60; 95% confidence interval (95% CI), 1.23-5.51; P-trend < 0.01; RR, 3.07; 95% CI, 1.35-6.98; P-trend < 0.003; and RR, 2.12; 95% CI, 0.98-4.57; P-trend < 0.004]. In contrast, BMI and waist circumference were inversely related to ESCC risk, whereas WHR showed no association with ESCC. In stratified analyses, BMI and waist circumference were significantly inversely related to ESCC only among smokers but not among nonsmokers. However, when controlled for BMI, we found positive associations for waist circumference and WHR with ESCC, and these associations were observed among smokers and nonsmokers. Conclusion: General and abdominal obesity were associated with higher EAC risk. Further, our study suggests that particularly an abdominal body fat distribution might also be a risk factor for ESCC. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2079-89)
47.	Steffen, Annika, et al. (författare) Development and Validation of a Risk Score Predicting Substantial Weight Gain over 5 Years in Middle-Aged European Men and Women 2013 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7 Tidskriftsartikel (refereegranskat)abstract Background: Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population. Methods: We used lifestyle and nutritional data from 53 degrees 758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining >= 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample). Results: Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of >= 200 points were 9% and 96%, respectively. Conclusion: The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score.
48.	van Boeckel, Petra G. A., et al. (författare) No association between educational level and pancreatic cancer incidence in the European Prospective Investigation into Cancer and Nutrition 2010 Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 34:6, s. 696-701 Tidskriftsartikel (refereegranskat)abstract Introduction: Until now, studies examining the relationship between socioeconomic status and pancreatic cancer incidence have been inconclusive. Aim: To prospectively investigate to what extent pancreatic cancer incidence varies according to educational level within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: In the EPIC study, socioeconomic status at baseline was measured using the highest level of education attained. Hazard ratios by educational level and a summary index, the relative indices of inequality (Rh), were estimated using Cox regression models stratified by age, gender, and center and adjusted for known risk factors. In addition, we conducted separate analyses by age, gender and geographical region. Results: Within the source population of 407, 944 individuals at baseline, 490 first incident primary pancreatic adenocarcinoma cases were identified in 9 European countries. The crude difference in risk of pancreatic cancer according to level of education was small and not statistically significant (RII = 1.14, 95% CI 0.80-1.62). Adjustment for known risk factors reduced the inequality estimates to only a small extent. In addition, no statistically significant associations were observed for age groups (adjusted RII <= (60) (years) = 0.85, 95% CI 0.44-1.64, adjusted RII> 60 years = 1.18, 95% CI 0.73-1.90), gender (adjusted RIImale = 1.20, 95% CI 0.68-2.10, adjusted RIIfemale = 0.96, 95% CI 0.56-1.62) or geographical region (adjusted RIINorthern Europe = 1.14, 95% CI 0.81-1.61, adjusted RIIMiddle (Europe) = 1.72, 95% CI 0.93-3.19, adjusted RIISouthern Europe = 0.75, 95% CI 0.32-1.80). Conclusion: Despite large educational inequalities in many risk factors within the EPIC study, we found no evidence for an association between educational level and the risk of developing pancreatic cancer in this European cohort. (C) 2010 Elsevier Ltd. All rights reserved.
49.	Vermeulen, Esther, et al. (författare) Dietary Flavonoid Intake and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Cohort 2013 Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 178:4, s. 570-581 Tidskriftsartikel (refereegranskat)abstract We prospectively investigated dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,312 adult subjects from 10 European countries. At baseline, country-specific validated dietary questionnaires were used. During a mean follow-up of 11 years (1992-2010), there were 341 incident esophageal cancer cases, of which 142 were esophageal adenocarcinoma (EAC), 176 were esophageal squamous cell carcinoma (ESCC), and 23 were other types of esophageal cancer. In crude models, a doubling in total dietary flavonoid intake was inversely associated with esophageal cancer risk (hazard ratio (HR) (log(2))=0.87, 95% confidence interval (CI): 0.78, 0.98) but not in multi-variable models (HR (log(2))=0.97, 95% CI: 0.86, 1.10). After covariate adjustment, no statistically significant association was found between any flavonoid subclass and esophageal cancer, EAC, or ESCC. However, among current smokers, flavonols were statistically significantly associated with a reduced esophageal cancer risk (HR (log(2)) = 0.72, 95% CI: 0.56, 0.94), whereas total flavonoids, flavanols, and flavan-3-ol monomers tended to be inversely associated with esophageal cancer risk. No associations were found in either never or former smokers. These findings suggest that dietary flavonoid intake was not associated with overall esophageal cancer, EAC, or ESCC risk, although total flavonoids and some flavonoid subclasses, particularly flavonols, may reduce the esophageal cancer risk among current smokers.
50.	Zamora-Ros, Raul, et al. (författare) Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study 2013 Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 139:1, s. 163-176 Tidskriftsartikel (refereegranskat)abstract Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.

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