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  • 1
    Keywords: DOSE-RESPONSE ; POSTMENOPAUSAL WOMEN ; REPRODUCTIVE FACTORS ; PHYSICAL-ACTIVITY ; BODY-MASS INDEX ; SEX-HORMONES ; SELF-REPORTED SMOKING ; TREND ANALYSIS ; OXFORD PARTICIPANTS ; EXOGENOUS HORMONE USE
    Abstract: Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip ratio, waist-height ratio, body mass index (BMI), recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight [1.04 (1.01-1.07) per 5 kilo], BMI [1.05 (1.02-1.08) per 2 units], waist circumference [1.04 (1.01-1.08) per 5 cm], waist-hip ratio (1.07 (1.02-1.13) per 0.05 unit] and waist-height ratio [1.07 (1.01-1.13) per 0.05 unit] in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p = 0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking.
    Type of Publication: Journal article published
    PubMed ID: 24771290
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  • 2
    Keywords: THERAPY ; HEALTH ; WOMEN
    Abstract: BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with 〈5 years of use (RR 1.43, 95% CI 1.31-1.56; p〈0.0001). Combining current-or-recent use (any duration, but stopped 〈5 years before diagnosis) resulted in an RR of 1.37 (95% CI 1.29-1.46; p〈0.0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p〈0.0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40-1.66; p〈0.0001) and endometrioid (1.42, 1.20-1.67; p〈0.0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1.25, 95% CI 1.07-1.46, p=0.005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK.
    Type of Publication: Journal article published
    PubMed ID: 25684585
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  • 3
    Keywords: CANCER ; THERAPY ; INFORMATION ; COHORT ; DISEASE ; incidence ; RISK ; RISK-FACTORS ; BREAST ; BREAST-CANCER ; DESIGN ; AGE ; WOMEN ; PROSPECTIVE COHORT ; smoking ; cancer risk ; UNITED-STATES ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; BIRTH COHORT ; POSTMENOPAUSAL WOMEN ; MASS INDEX ; ORAL-CONTRACEPTIVE USE ; REQUIRING PROLONGED OBSERVATION ; METAANALYSIS ; HORMONAL FACTORS ; ANTHROPOMETRIC MEASURES ; EPITHELIAL OVARIAN
    Abstract: BACKGROUND: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. METHODS AND FINDINGS: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p〈0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p〈0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p〈0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. CONCLUSIONS: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. Please see later in the article for the Editors' Summary.
    Type of Publication: Journal article published
    PubMed ID: 22606070
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  • 4
    Keywords: RISK-FACTORS ; prevention ; COLON-CANCER ; MYOCARDIAL-INFARCTION ; nutrition ; PHYSICAL-ACTIVITY ; METAANALYSIS ; RECTAL CANCERS ; PROPORTION ; Attributable risk
    Abstract: Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend 〈0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend 〈0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend 〈0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. Conclusions: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
    Type of Publication: Journal article published
    PubMed ID: 25319089
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  • 5
    Keywords: DISEASE ; colon ; C-REACTIVE PROTEIN ; ADAPTIVE IMMUNITY ; OXIDATIVE STRESS ; nutrition ; RECTAL-CANCER ; SERUM ; URINARY NEOPTERIN ; VITAMIN STATUS
    Abstract: BACKGROUND: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. RESULTS: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. CONCLUSIONS: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
    Type of Publication: Journal article published
    PubMed ID: 25713165
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  • 6
    Abstract: Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. Design: Prospective cohort study. Setting: 10 European countries. Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend 〈 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend 〈 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend 〈 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend 〈 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; gamma-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country. Primary Funding Source: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.
    Type of Publication: Journal article published
    PubMed ID: 28693038
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  • 7
    Keywords: EXPRESSION ; PATHWAY ; ASSOCIATION ; POLYMORPHISMS ; prostate cancer ; nutrition ; FOXO TRANSCRIPTION FACTORS ; forkhead box ; genetic variability ; HUMAN LONGEVITY ; SIRT1
    Abstract: Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men
    Type of Publication: Journal article published
    PubMed ID: 21725602
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  • 8
    Abstract: Diets high in red or processed meat have been associated positively with some cancers, and several possible underlying mechanisms have been proposed, including iron-related pathways. However, the role of meat intake in adult glioma risk has yielded conflicting findings because of small sample sizes and heterogeneous tumour classifications. The aim of this study was to examine red meat, processed meat and iron intake in relation to glioma risk in the European Prospective Investigation into Cancer and Nutrition study. In this prospective cohort study, 408 751 individuals from nine European countries completed demographic and dietary questionnaires at recruitment. Multivariable Cox proportional hazards models were used to examine intake of red meat, processed meat, total dietary iron and haem iron in relation to incident glioma. During an average follow-up of 14.1 years, 688 incident glioma cases were diagnosed. There was no evidence that any of the meat variables (red, processed meat or subtypes of meat) or iron (total or haem) were associated with glioma; results were unchanged when the first 2 years of follow-up were excluded. This study suggests that there is no association between meat or iron intake and adult glioma. This is the largest prospective analysis of meat and iron in relation to glioma and as such provides a substantial contribution to a limited and inconsistent literature.
    Type of Publication: Journal article epub ahead of print
    PubMed ID: 27845960
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  • 9
    Abstract: Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95%CI]=0.79-0.93; qvalue =0.01) and homovanillic acid (OR per log2 -value, 1.46, 95%CI=1.16-1.84; qvalue =0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR=0.61, 95%CI=0.41-0.91, ptrend =0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR=1.72, 95%CI=1.17-2.53, ptrend 〈0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk, of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis. This article is protected by copyright. All rights reserved.
    Type of Publication: Journal article epub ahead of print
    PubMed ID: 29696648
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  • 10
    Keywords: measurement ; CANCER ; Germany ; COHORT ; INDEX ; ASSOCIATION ; PLASMA ; AGE ; WOMEN ; MEN ; smoking ; COUNTRIES ; MALES ; PROSTATE-CANCER ; MARKERS ; SWEDEN ; REGION ; REGIONS ; NETHERLANDS ; ALCOHOL ; GREECE ; CONSUMPTION ; EPIC ; European Prospective Investigation into Cancer and Nutrition ; FRUIT ; nutrition ; EUROPE ; antioxidants ; DENMARK ; BETA-CAROTENE ; VITAMIN-E ; ALPHA-TOCOPHEROL ; alpha-carotene ; beta-cryptoxanthin ; carotenoids ; lutein ; LYCOPENE ; MASS INDEX ; MASSES ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; RETINOL ; SEASONAL-VARIATION ; SERUM CONCENTRATIONS ; zeaxanthin
    Abstract: Background: In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet-disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe. Objective: Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Plasma levels of six carotenoids-alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin-were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids. Results: Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35 mumol l(-1) for men in Malmo, Sweden vs. 2.79 mumol l(-1) for men in Ragusa/Naples, Italy; 1.61 mumol l(-1) for women in The Netherlands vs. 3.52 mumol l(-1) in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (alpha-carotene: 0.06 mumol l(-1) for men in Murcia, Spain vs. 0.25 mumol l(-1) for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R-2=27.3%), followed by BMI (partial R-2=5.2%), gender (partial R-2=2.7%) and smoking status (partial R-2=2.8%). Females had higher total carotenoid levels than males across Europe. Conclusions: Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe
    Type of Publication: Journal article published
    PubMed ID: 15369608
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