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51.	Kovacs, E., et al. (author) Adherence to combined lifestyle factors and their contribution to obesity in the IDEFICS study 2015 In: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:Suppl. 2, s. 138-150 Journal article (peer-reviewed)abstract BackgroundThe Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study investigated the aetiology of childhood obesity and developed a primary prevention programme. MethodsPre-intervention adherence to key behaviours related to childhood obesity, namely water/sweetened drink, fruit/vegetable consumption, daily TV time, physical activity, family time and adequate sleep duration, was measured at baseline. Adherence to international recommendations was converted into a composite score ranging from 0 (none) to 6 (adhering to all). Data on adherence were available for 7,444 to 15,084 children aged 2-9.9years, depending on the behaviour. By means of multi-level logistic regression models adjusted for age, sex and country, we calculated odds ratios (OR) and 95% confidence intervals (CI) to estimate the relationship between adherence to these recommendations and the risk of being overweight/obese. ResultsAdherence ranged from 15.0% (physical activity) to 51.9% (TV time). As adherence increased, a lower chance of being overweight/obese was observed; adhering to only one key behaviour (score=1) meant an OR=0.81 (CI: 0.65-1.01) compared with non-adherence (score=0), while adhering to more than half of the key behaviours (score4) halved the chance for overweight/obesity (OR=0.54, CI: 0.37-0.80). Adherence to physical activity, TV and sleep recommendations was the main driver reducing the chance of being overweight. Overweight/obese children were more likely not to adhere to at least one of the recommended behaviours (19.8%) than normal-weight/thin children (12.9%) ConclusionThe selected key behaviours do not contribute equally to a reduced chance of being overweight. Future interventions may benefit most from moving more, reducing TV time and getting adequate sleep. (c) 2015 World Obesity
52.	Mayén, Ana Lucia, et al. (author) A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk 2022 In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:9, s. 915-929 Journal article (peer-reviewed)abstract Background: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Objective: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Methods: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Results: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Conclusions: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.
53.	Nimptsch, Katharina, et al. (author) Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer : a Mendelian Randomization analysis using data from three large cohort studies 2017 In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 32:5, s. 419-430 Journal article (peer-reviewed)abstract Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.
54.	Obón-Santacana, M., et al. (author) Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort 2014 In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 111:5, s. 987-997 Journal article (peer-reviewed)abstract BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n = 1382) or type-I EC risk (n = 627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n = 203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.
55.	Pala, V., et al. (author) Dietary patterns and longitudinal change in body mass in European children: a follow-up study on the IDEFICS multicenter cohort 2013 In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 67:10, s. 1042-1049 Journal article (peer-reviewed)abstract BACKGROUND/OBJECTIVES: Longitudinal studies investigating dietary patterns (DPs) and their association with childhood overweight/obesity are lacking in Europe. We identified DPs and investigated their association with overweight/obesity and changes in body mass index (BMI) in a cohort of European children. SUBJECTS/METHODS: Children aged 2-10 from eight European countries were recruited in 2007-2008. Food frequency questionnaires were collected from 14 989 children. BMI and BMI z-scores were derived from height and weight and were used to identify overweight/obese children. After 2 years (mean), anthropometric measurements were repeated in 9427 children. Principal component analysis was used to identify DPs. Simplified DPs (SDPs) were derived from DPs. Adjusted odds ratios (ORs) for overweight/obesity with increasing DP intake were estimated using multilevel logistic regression. Associations of BMI change with DP and SDP were assessed by multilevel mixed regression. Models were adjusted for baseline BMI, age, sex, physical activity and family income. RESULTS: Four DPs were identified that explained 25% of food intake variance: snacking, sweet and fat, vegetables and wholemeal, and protein and water. After 2 years, 849(9%) children became overweight/obese. Children in the highest vegetables and wholemeal tertile had lower risk of becoming overweight/obese (OR: 0.69, 95% confidence intervals (CIs): 0.54-0.88). Children in the highest SDP tertile of vegetables and wholemeal had similarly lower risk of becoming overweight/obese (OR: 0.64, 95% CIs: 0.51-0.82), and their BMI increased by 0.7 kg/m(2) over the study period-significantly less than the increase in the lowest tertile (0.84 kg/m(2)). CONCLUSIONS: Our findings suggest that promoting a diet rich in vegetables and wholemeal cereals may counteract overweight/obesity in children.
56.	Pala, Valeria, et al. (author) Meat, eggs, dairy products, and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 2009 In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 90:3, s. 602-612 Journal article (peer-reviewed)abstract BACKGROUND: A Western diet is associated with breast cancer risk. OBJECTIVE: We investigated the relation of meat, egg, and dairy product consumption with breast cancer risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Between 1992 and 2003, information on diet was collected from 319,826 women. Disease hazard ratios were estimated with multivariate Cox proportional hazard models. RESULTS: Breast cancer cases (n = 7119) were observed during 8.8 y (median) of follow-up. No consistent association was found between breast cancer risk and the consumption of any of the food groups under study, analyzed by both categorical and continuous exposure variable models. High processed meat consumption was associated with a modest increase in breast cancer risk in the categorical model (hazard ratio: 1.10; 95% CI: 1.00, 1.20; highest compared with lowest quintile: P for trend = 0.07). Subgroup analyses suggested an association with butter consumption, limited to premenopausal women (hazard ratio: 1.28; 95% CI: 1.06, 1.53; highest compared with lowest quintile: P for trend = 0.21). Between-country heterogeneity was found for red meat (Q statistic = 18.03; P = 0.05) and was significantly explained (P = 0.023) by the proportion of meat cooked at high temperature. CONCLUSIONS: We have not consistently identified intakes of meat, eggs, or dairy products as risk factors for breast cancer. Future studies should investigate the possible role of high-temperature cooking in the relation of red meat intake with breast cancer risk.
57.	Romaguera, Dora, et al. (author) Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? : Results from the EPIC study 2012 In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:1, s. 150-163 Journal article (peer-reviewed)abstract Background: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Design: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. Results: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% Cl: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. Conclusion: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer. Am J Clin Nutr 2012;96:150-63.
58.	Santaliestra-Pasias, A. M., et al. (author) Clustering of lifestyle behaviours and relation to body composition in European children. The IDEFICS study 2015 In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 69:7, s. 811-816 Journal article (peer-reviewed)abstract BACKGROUND: Dietary patterns, physical activity (PA) and sedentary behaviours are some of the main behavioural determinants of obesity; their combined influence in children has been addressed in a limited number of studies. SUBJECTS/METHODS: Children (16 228) aged 2-9 years old from eight European countries participated in the baseline survey of the IDEFICS study. A subsample of 11 674 children (50.8% males) were included in the present study. Children's food and beverage consumption (fruit and vegetables (F&V) and sugar-sweetened beverages (SSBs)), PA and sedentary behaviours were assessed via parental questionnaires. Sex-specific cluster analysis was applied to identify behavioural clusters. Analysis of covariance and logistic regression were applied to examine the association between behavioural clusters and body composition indicators (BCIs). RESULTS: Six behavioural clusters were identified (C1-C6) both in boys and girls. In both sexes, clusters characterised by high level of PA (C1 and C3) included a large proportion of older children, whereas clusters characterised by low SSB consumption (C5 and C6) included a large proportion of younger children. Significant associations between derived clusters and BCI were observed only in boys; those boys in the cluster with the highest time spent in sedentary activities and low PA had increased odds of having a body mass index z-score (odds ratio (OR) = 1.33; 95% confidence interval (CI) = (1.01, 1.74)) and a waist circumference z-score (OR = 1.41; 95% CI = (1.06, 1.86)) greater than one. CONCLUSION: Clusters characterised by high sedentary behaviour, low F&V and SSB consumption and low PA turned out to be the most obesogenic factors in this sample of European children.
59.	Santaliestra-Pasias, AM, et al. (author) Physical activity and sedentary behaviour in European children: the IDEFICS study. 2014 In: Public Health Nutrition. - 1368-9800. ; 17:10, s. 2295-2306 Journal article (peer-reviewed)abstract OBJECTIVE: To estimate the prevalence of physical activity and sedentary behaviours in European children, and to evaluate the relationship between media availability in personal space and physical activity in relation to total screen time. DESIGN: Data from the baseline IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cross-sectional survey. Information on hours of television/digital video disk/video viewing and computer/games-console use (weekday and weekend days), media device availability in personal space, sports club membership, hours of active organized play and commuting (to and from school) were assessed via a self-reported parental questionnaire. Total screen time was defined as the sum of daily media use and subsequently dichotomized into meeting or not meeting the guidelines of the American Academy of Pediatrics. SETTING: Eight survey centres (Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary and Spain). SUBJECTS: Children (n 15 330; 51 % males) aged 2-10 years. RESULTS: Percentage of children engaged in total screen time for >2 h/d was higher on weekend days (52 % v. 20 % on weekdays) and in the older group (71 % in males; 57 % in females), varying by country. Children with a television set in their bedroom were more likely not to meet the screen time recommendations (OR = 1·54; 95 % CI 1·60, 1·74). CONCLUSIONS: Approximately a third of the children failed to meet current screen time recommendations. Availability of a television set in personal space increased the risk of excess total screen time. This information could be used to identify potential targets for public health promotion actions of young population groups.
60.	Sieri, Sabina, et al. (author) Glycemic index, glycemic load, and risk of coronary heart disease : a pan-European cohort study 2020 In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 112:3, s. 631-643 Journal article (peer-reviewed)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.
61.	Sieri, S, et al. (author) Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project 2002 In: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1287-1296 Journal article (peer-reviewed)abstract Objective. The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases. Methods: We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex. Results: Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day(-1)) for men and in Danish centres (Copenhagen, 20.9 g day(-1)) for women. The lowest total alcohol intake was in the Swedish centres (Umea, 10.2 g day(-1)) in men and in Greek women (3.4 g day(-1)). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes. Conclusions: The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.
62.	Tong, Tammy Y. N., et al. (author) Dietary amino acids and risk of stroke subtypes : a prospective analysis of 356,000 participants in seven European countries 2024 In: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 63, s. 209-220 Journal article (peer-reviewed)abstract Purpose: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study.Methods: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants.Results: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing.Conclusion: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.
63.	Vergnaud, Anne-Claire, et al. (author) Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe : results from the European Prospective Investigation into Nutrition and Cancer cohort study 2013 In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 97:5, s. 1107-1120 Journal article (peer-reviewed)abstract Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.
64.	Vrieling, Alina, et al. (author) Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition 2009 In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:8, s. 1926-1934 Journal article (peer-reviewed)abstract Many case-control studies have suggested that higher consumption of fruit and vegetables is associated with a lower risk or pancreatic cancer, whereas cohort studies do not support such an association. We examined the associations of the consumption of. fruits and vegetables and their main subgroups with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is comprised of over 520,000 Subjects recruited from 10 European countries. The present study included 555 exocrine pancreatic cancer cases after an average follow-up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models, stratified by age at recruitment, gender, and study center. and adjusted for total energy intake, weight, height, history of diabetes mellitus, and smoking status. Total consumption of fruit and vegetables, combined or separately, as well as subgroups of vegetables and fruits were unrelated to risk of pancreatic cancer. Hazard ratios (95% CI) for the highest versus the lowest quartile were 0.92 (0.68-1.25) for total fruit and vegetables combined, 0.99 (0.73-1.33) for total vegetables, and 1.02 (0.77-1.36) for total fruits. Stratification by gender or smoking status, restriction to microscopically verified cases, and exclusion of the first 2 years of follow-up (lid not materially change the results. These results from a large European prospective cohort Suggest that higher consumption of fruit and vegetables is not associated with decreased risk of pancreatic cancer. (C) 2008 Wiley-Liss, Inc.
65.	Wentzensen, Nicolas A., et al. (author) Ovarian cancer risk factors by histologic subtypes : evidence for etiologic heterogeneity 2015 In: Cancer Research. - 0008-5472 .- 1538-7445. ; 75 Journal article (other academic/artistic)
66.	Wentzensen, Nicolas, et al. (author) Ovarian Cancer Risk Factors by Histologic Subtype : An Analysis From the Ovarian Cancer Cohort Consortium 2016 In: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 34:24, s. 2888-2898 Journal article (peer-reviewed)abstract Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
67.	Wu, Wendy Yi-Ying, et al. (author) Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers : A retrospective nested case-control study in two prospective cohorts 2023 In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:9, s. 2002-2010 Journal article (peer-reviewed)abstract The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.
68.	Zeleniuch-Jacquotte, A, et al. (author) Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer 2011 In: British Journal of Cancer. - London : Harcourt Publishers. - 0007-0920 .- 1532-1827. ; 105:9, s. 1458-1464 Journal article (peer-reviewed)abstract Background: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful. Methods: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay. Results: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio. Conclusion: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.
69.	Zheng, Ju-Sheng, et al. (author) Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes : EPIC-InterAct Case-Cohort Study 2019 In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:4, s. 1293-1303 Journal article (peer-reviewed)abstract Background: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D.Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography–mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis.Results: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)].Conclusions: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.
70.	Zheng, Ju Sheng, et al. (author) Plasma Vitamin C and type 2 diabetes : Genome-wide association study and mendelian randomization analysis in European populations 2021 In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:1, s. 98-106 Journal article (peer-reviewed)abstract OBJECTIVE Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS We identified 11 genomic regions associated with plasma vitamin C (P < 5 ☓ 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
71.	Zhong, Jun, et al. (author) A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer 2020 In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 112:10 Journal article (peer-reviewed)abstract Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
72.	Zuo, Hui, et al. (author) Results from the European Prospective Investigation into Cancer and Nutrition Link Vitamin B6 Catabolism and Lung Cancer Risk 2018 In: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:1, s. 302-308 Journal article (peer-reviewed)abstract Circulating pyridoxal-5′-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose–response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27–1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.

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