Timothy J Key

University of Oxford, Oxford, England, United Kingdom

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Publications (329)2269.76 Total impact

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    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 investigate 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 and design 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 100 μg/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 adjusting for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and γ-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 (Pinteraction < 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.
    No preview · Article · Feb 2016 · Diabetes Care
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    ABSTRACT: Introduction: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. Methods: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI). Results: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09). Conclusion: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.
    No preview · Article · Feb 2016
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    ABSTRACT: Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity. Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer. Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided. Results: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution). Conclusion: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.
    Full-text · Article · Jan 2016 · American Journal of Clinical Nutrition
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    ABSTRACT: The aim of this study was to investigate differences in dietary intakes between 30 251 participants in the EPIC-Oxford study, comprising 18 244 meat-eaters, 4 531 fish-eaters, 6 673 vegetarians and 803 vegans aged 30-90 years, who completed semi-quantitative food frequency questionnaires. We hypothesized that these groups characterized by varying degrees of animal product exclusion have significantly different intakes of many nutrients, with possible implications for dietary adequacy and compliance with population dietary goals. Nutrient intakes were estimated including fortification in foods, but excluding dietary supplements. Dietary supplementation practices were also evaluated. Highly significant differences were found in estimated nutrient intakes between meat-eaters and vegans, with fish-eaters and vegetarians usually having intermediate values. Meat-eaters had the highest energy intakes, followed by fish-eaters and vegetarians, while vegans had the lowest intakes. Vegans had the highest intakes of polyunsaturated fatty acids, dietary fiber, vitamins C, E, folate, magnesium, iron and copper. Meat eaters had the highest intake of saturated fatty acids, protein, vitamins B2, B12, D, zinc and iodine. Fish-eaters had the highest intakes of calcium and selenium. There were no statistically significant differences in sodium and potassium intakes between dietary groups. With the exception of sodium intake, compliance with population dietary goals was high across diet groups. The results suggested a high prevalence of inadequacy for dietary vitamin B12 and iodine in vegans. The diet groups under study showed striking differences in dietary intakes, with possible implications for compliance with dietary recommendations, as well as cardiometabolic diseases risk.
    Preview · Article · Jan 2016 · Nutrition Research
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    ABSTRACT: Background: Specific nutrients or foods have been inconsistently associated with ulcerative colitis (UC) or Crohn's disease (CD) risks. Thus, we investigated associations between diet as a whole, as dietary patterns, and UC and CD risks. Methods: Within the prospective EPIC (European Prospective Investigation into Cancer) study, we set up a nested matched case-control study among 366,351 participants with inflammatory bowel disease data, including 256 incident cases of UC and 117 of CD, and 4 matched controls per case. Dietary intake was recorded at baseline from validated food frequency questionnaires. Incidence rate ratios of developing UC and CD were calculated for quintiles of the Mediterranean diet score and a posteriori dietary patterns produced by factor analysis. Results: No dietary pattern was associated with either UC or CD risks. However, when excluding cases occurring within the first 2 years after dietary assessment, there was a positive association between a "high sugar and soft drinks" pattern and UC risk (incidence rate ratios for the fifth versus first quintile, 1.68 [1.00-2.82]; Ptrend = 0.02). When considering the foods most associated with the pattern, high consumers of sugar and soft drinks were at higher UC risk only if they had low vegetables intakes. Conclusions: A diet imbalance with high consumption of sugar and soft drinks and low consumption of vegetables was associated with UC risk. Further studies are needed to investigate whether microbiota alterations or other mechanisms mediate this association.
    No preview · Article · Dec 2015 · Inflammatory Bowel Diseases
  • Paul N Appleby · Timothy J Key
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    ABSTRACT: Vegetarians, who do not eat any meat, poultry or fish, constitute a significant minority of the world's population. Lacto-ovo-vegetarians consume dairy products and/or eggs, whereas vegans do not eat any foods derived wholly or partly from animals. Concerns over the health, environmental and economic consequences of a diet rich in meat and other animal products have focussed attention on those who exclude some or all of these foods from their diet. There has been extensive research into the nutritional adequacy of vegetarian diets, but less is known about the long-term health of vegetarians and vegans. We summarise the main findings from large cross-sectional and prospective cohort studies in western countries with a high proportion of vegetarian participants. Vegetarians have a lower prevalence of overweight and obesity and a lower risk of IHD compared with non-vegetarians from a similar background, whereas the data are equivocal for stroke. For cancer, there is some evidence that the risk for all cancer sites combined is slightly lower in vegetarians than in non-vegetarians, but findings for individual cancer sites are inconclusive. Vegetarians have also been found to have lower risks for diabetes, diverticular disease and eye cataract. Overall mortality is similar for vegetarians and comparable non-vegetarians, but vegetarian groups compare favourably with the general population. The long-term health of vegetarians appears to be generally good, and for some diseases and medical conditions it may be better than that of comparable omnivores. Much more research is needed, particularly on the long-term health of vegans.
    No preview · Article · Dec 2015 · Proceedings of The Nutrition Society
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    ABSTRACT: Background: Vegetarians and others who do not eat meat have been observed to have lower incidence rates than meat eaters of some chronic diseases, but it is unclear whether this translates into lower mortality. Objective: The purpose of this study was to describe mortality in vegetarians and comparable nonvegetarians in a large United Kingdom cohort. Design: The study involved a pooled analysis of data from 2 prospective studies that included 60,310 persons living in the United Kingdom, comprising 18,431 regular meat eaters (who ate meat ≥5 times/wk on average), 13,039 low (less-frequent) meat eaters, 8516 fish eaters (who ate fish but not meat), and 20,324 vegetarians (including 2228 vegans who did not eat any animal foods). Mortality by diet group for each of 18 common causes of death was estimated with the use of Cox proportional hazards models. Results: There were 5294 deaths before age 90 in >1 million y of follow-up. There was no significant difference in overall (all-cause) mortality between the diet groups: HRs in low meat eaters, fish eaters, and vegetarians compared with regular meat eaters were 0.93 (95% CI: 0.86, 1.00), 0.96 (95% CI: 0.86, 1.06), and 1.02 (95% CI: 0.94, 1.10), respectively; P-heterogeneity of risks = 0.082. There were significant differences in risk compared with regular meat eaters for deaths from circulatory disease [higher in fish eaters (HR: 1.22; 95% CI: 1.02, 1.46)]; malignant cancer [lower in fish eaters (HR: 0.82; 95% CI: 0.70, 0.97)], including pancreatic cancer [lower in low meat eaters and vegetarians (HR: 0.55; 95% CI: 0.36, 0.86 and HR: 0.48; 95% CI: 0.28, 0.82, respectively)] and cancers of the lymphatic/hematopoietic tissue [lower in vegetarians (HR: 0.50; 95% CI: 0.32, 0.79)]; respiratory disease [lower in low meat eaters (HR: 0.70; 95% CI: 0.53, 0.92)]; and all other causes [lower in low meat eaters (HR: 0.74; 95% CI: 0.56, 0.99)]. Further adjustment for body mass index left these associations largely unchanged. Conclusions: United Kingdom-based vegetarians and comparable nonvegetarians have similar all-cause mortality. Differences found for specific causes of death merit further investigation.
    No preview · Article · Dec 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842, 149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/d: advanced 0.83, 0.70-0.99; trend test p-value 0.29), fatal, 0.69, 0.59-0.82, trend test p-value 0.16). Participants who ate ≥25 vs <5 g/d of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (MVRR: advanced 1.14, 1.01-1.28, trend test p-value 0.01; fatal 1.14, 1.00-1.30, trend test p-value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · International Journal of Cancer
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    ABSTRACT: Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85-0.96; P for trend = 0.038). Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.
    Preview · Article · Dec 2015 · BMC Medicine
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    ABSTRACT: Background: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk. Objective: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk. Design: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors. Results: After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk. Conclusion: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk.
    No preview · Article · Nov 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Background: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. Objective: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. Design: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate–controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Results: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Conclusions: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans.
    Full-text · Article · Oct 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Background: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Objective: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors. Design: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets. Results: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest vs. the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest vs. the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest vs. the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk. Conclusions: Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.
    No preview · Article · Oct 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). We observed no significant association between genetic variants and prostate cancer survival. Common genetic variants with large impact on prostate cancer survival were not observed in this study. Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Copyright © 2015, American Association for Cancer Research.
    Full-text · Article · Aug 2015 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Objective Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples. Methods Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models. Results In fasting samples, a median ICC of 0.70 was observed. ICC values were <0.50 for 48% of amino acids, 27% of acylcarnitines, 18% of lysophosphatidylcholines and 4% of phosphatidylcholines. In non-fasting samples, the median ICC was 0.54. ICC values were <0.50 for 71% of acylcarnitines, 48% of amino acids, 44% of biogenic amines, 36% of sphingomyelins, 34% of phosphatidylcholines and 33% of lysophosphatidylcholines. Overall, reproducibility was lower in non-fasting as compared to fasting samples, with a statistically significant difference for 19–36% of acylcarnitines, phosphatidylcholines and sphingomyelins. Conclusion A single measurement per individual may be sufficient for the study of 73% and 52% of the metabolites showing ICCs >0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting.
    Full-text · Article · Aug 2015 · PLoS ONE
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    ABSTRACT: ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95%CI = 0.87-1.08; Type B: OR = 0.92, 95%CI =n0.77-1.09; Type AB: OR = 1.25, 95%CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. ABO blood type was not associated with risk of aggressive prostate cancer. Prostate 9999: 1-5, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2015 · The Prostate
  • Wenji Guo · Gillian K. Reeves · Timothy J. Key

    No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: It is estimated that over half the population of the European Union (EU) is overweight or obese due to an imbalance between energy expenditure and energy intake; this is related to an obesogenic environment of sociocultural, economic and marketing challenges to the control of body weight. Excess body fat is associated with nine cancer sites - oesophagus, colorectum, gall bladder, pancreas, postmenopausal breast, endometrium, ovary, kidney and prostate (advanced) - and 4-38% of these cancers (depending on site and gender) can be attributed to overweight/obesity status. Metabolic alterations which accompany excess body weight are accompanied by increased levels of inflammation, insulin, oestrogens and other hormonal factors. There are some indications that intentional weight loss is associated with reduced cancer incidence (notably in postmenopausal breast and endometrial cancers). Excess body weight is also a risk factor for several other diseases, including diabetes and heart disease, and is related to higher risk of premature death. In reviewing the current evidence related to excess body fat and cancer, the European Code against Cancer Nutrition Working Group has developed the following recommendation: 'Take action to be a healthy body weight'. Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd.. All rights reserved.
    Full-text · Article · Jul 2015
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    ABSTRACT: Physical activity is a complex, multidimensional behavior, the precise measurement of which is challenging in free-living individuals. Nonetheless, representative survey data show that 35% of the European adult population is physically inactive. Inadequate levels of physical activity are disconcerting given substantial epidemiologic evidence showing that physical activity is associated with decreased risks of colon, endometrial, and breast cancers. For example, insufficient physical activity levels are thought to cause 9% of breast cancer cases and 10% of colon cancer cases in Europe. By comparison, the evidence for a beneficial effect of physical activity is less consistent for cancers of the lung, pancreas, ovary, prostate, kidney, and stomach. The biologic pathways underlying the association between physical activity and cancer risk are incompletely defined, but potential etiologic pathways include insulin resistance, growth factors, adipocytokines, steroid hormones, and immune function. In recent years, sedentary behavior has emerged as a potential independent determinant of cancer risk. In cancer survivors, physical activity has shown positive effects on body composition, physical fitness, quality of life, anxiety, and self-esteem. Physical activity may also carry benefits regarding cancer survival, but more evidence linking increased physical activity to prolonged cancer survival is needed. Future studies using new technologies - such as accelerometers and e-tools - will contribute to improved assessments of physical activity. Such advancements in physical activity measurement will help clarify the relationship between physical activity and cancer risk and survival. Taking the overall existing evidence into account, the fourth edition of the European Code against Cancer recommends that people be physically active in everyday life and limit the time spent sitting.
    Full-text · Article · Jul 2015
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    ABSTRACT: Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n=100) and the thousands of surrogate SNPs in linkage disequilibrium. Here we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8,600/6,946), African (cases/controls: 5,327/5,136), Japanese (cases/controls: 2,563/4,391) and Latino (cases/controls: 1,034/1,046) ancestry. Markers at 55 regions passed a region-specific significance threshold (p-value cutoff range: 3.9×10(-4)-5.6×10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (p<5.0×10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with p-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Jul 2015 · Human Molecular Genetics
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    Dataset: IJC2015

    Full-text · Dataset · Jun 2015

Publication Stats

18k Citations
2,269.76 Total Impact Points

Institutions

  • 1999-2016
    • University of Oxford
      • • Cancer Epidemiology Unit
      • • Cancer Research Group
      Oxford, England, United Kingdom
  • 2014
    • Second University of Naples
      Caserta, Campania, Italy
    • Nuffield Health
      Londinium, England, United Kingdom
  • 2012-2014
    • University of Ioannina
      • Department of Hygiene and Epidemiology
      Yannina, Epirus, Greece
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Provincie Utrecht, Netherlands
  • 2011
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2008
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
    • Imperial College London
      • Department of Epidemiology and Biostatistics
      Londinium, England, United Kingdom
  • 2007
    • Aarhus University
      • Department of Epidemiology and Social Medicine
      Aarhus, Central Jutland, Denmark
  • 1997-2007
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
  • 2006
    • University of Florence
      Florens, Tuscany, Italy
    • Loma Linda University
      • Department of Nutrition
      لوما ليندا، كاليفورنيا, California, United States
  • 2005
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 2003-2005
    • University of Naples Federico II
      Napoli, Campania, Italy
    • Cancer Research UK
      Londinium, England, United Kingdom