Kay-Tee Khaw

National Cancer Institute (USA), 베서스다, Maryland, United States

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Publications (726)5677.67 Total impact

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    ABSTRACT: Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol concentrations. We analysed 2,937 SNPs in 6,608 endometrial cancer cases and 37,925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10-11). SNP rs727479 was also among those most strongly associated with circulating estradiol concentrations in 2,767 post-menopausal controls (P=7.4x10-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on estradiol concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by estradiol. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.
    Endocrine Related Cancer 11/2015; DOI:10.1530/ERC-15-0386 · 4.81 Impact Factor
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    ABSTRACT: Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
    American Journal of Clinical Nutrition 11/2015; DOI:10.3945/ajcn.115.116095 · 6.77 Impact Factor
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    ABSTRACT: Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (±3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR=0.80, 95% CI=0.62-1.03) and a significant survival benefit in long-term MHT users (⩾5 years use vs never use, HR=0.70, 95% CI=0.50-0.99, Ptrend=0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.British Journal of Cancer advance online publication, 10 November 2015; doi:10.1038/bjc.2015.377 www.bjcancer.com.
    British Journal of Cancer 11/2015; DOI:10.1038/bjc.2015.377 · 4.84 Impact Factor
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    ABSTRACT: Background: Vitamin C sufficiency may help prevent osteoporosis and fractures by mediating osteoclastogenesis, osteoblastogenesis, and bone collagen synthesis. Objective: We determined whether dietary intakes and plasma concentrations of vitamin C were associated with a heel ultrasound and hip and spine fracture risks in older men and women. Design: Participants were recruited from the European Prospective Investigation into Cancer in Norfolk study with 7-d diet diary estimates of vitamin C intake and plasma concentrations. A random subset (4000 of 25,639 subjects) was available for the cross-sectional (ultrasound) study of broadband ultrasound attenuation (BUA) and velocity of sound (VOS), which were determined during the second health examination. The prospective (fracture) study was a case-cohort sample of all participants with a fracture up to March 2009 and the random subset (n = 5319). ANCOVA-determined associations between quintiles of vitamin C intake and plasma status with adjusted BUA and VOS and adjusted Prentice-weighted Cox proportional HRs were calculated for fracture risk. Results: Women were 58% of the population (39-79 y old), and the median follow-up was 12.6 y (range: 0-16 y). Positive associations across all quintiles of vitamin C intake but not plasma status were significant for VOS in men (β = 2.47 m/s, P = 0.008) and BUA in women (β = 0.82 dB/MHz, P = 0.004). Vitamin C intake was not associated with fracture risk, but there was an inverse association with plasma concentrations in men, with quintile 4 having significantly lower risks of hip fractures (HR: 0.35; 95% CI: 0.16, 0.80) and spine fractures (HR: 0.26; 95% CI: 0.10, 0.69) than quintile 1. Conclusions: Higher vitamin C intake was significantly associated with higher heel ultrasound measures in men and women, and higher plasma vitamin C concentrations were significantly associated with reduced fracture risk in men only. Our findings that vitamin C intake and status were inconsistently associated with bone health variables suggest that additional research is warranted.
    American Journal of Clinical Nutrition 11/2015; DOI:10.3945/ajcn.115.111971 · 6.77 Impact Factor
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    ABSTRACT: The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.
    Breast Cancer Research and Treatment 11/2015; 154(2). DOI:10.1007/s10549-015-3595-9 · 3.94 Impact Factor
  • Olivia Remes · Louise Lafortune · Kay-Tee Khaw · Carol Brayne ·

    The Lancet 11/2015; 386:S67. DOI:10.1016/S0140-6736(15)00905-8 · 45.22 Impact Factor
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    ABSTRACT: Purpose: Sedentariness has been proposed as an independent risk factor for poor health. However, few studies have considered associations of sedentary time with physical functional health independent of time spent in moderate-vigorous physical activity (MVPA). Methods: Community-based men and women (n=8623, 48-92 years old) in the European Prospective Investigation of Cancer-Norfolk study attended a health examination for objective measurement of physical capability, including grip strength (Smedley dynamometer, kg), usual walking speed (UWS, cm/s) and timed chair stands speed (TCSS, stands/minute). Of these, 4051 participants wore an accelerometer (GT1M Actigraph) for 7 days to estimate time spent in moderate-vigorous physical activity (MVPA, ≥1952 counts/minute) and sedentary (ST, <100 counts/minute). Relationships between physical capability outcomes and both MVPA and ST were explored using linear regression. The mutual independence of associations was also tested and ST-MVPA interactions were explored, using fractional polynomial models to account for non-linear associations. Results: Men in the highest compared to the lowest sex-specific quartile of MVPA were stronger (1.84 kg; 95% Confidence Interval [CI] 0.79, 2.89), had faster UWS (11.7 cm/s; 95% CI 8.4, 15.1) and faster TCSS (2.35 stands/minute; 95% CI 1.11, 3.59) after multivariable adjustment. Similarly women in the highest quartile of MVPA were stronger (2.47kg; 95% CI 1.79, 3.14), had faster UWS (15.5cm/s; 95% CI 12.4, 18.6) and faster TCSS (3.27stands/min; 95% CI 2.19, 4.25). Associations persisted after further adjustment for ST. Associations between higher ST and lower physical capability were also observed but these were attenuated after accounting for MVPA. Furthermore, no MVPA-ST interactions were observed (Pinteractions >0.05). Conclusions: More time spent in MVPA was associated with higher physical capability but there were no independent ST associations.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Medicine and science in sports and exercise 10/2015; DOI:10.1249/MSS.0000000000000785 · 3.98 Impact Factor
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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.
    American Journal of Clinical Nutrition 10/2015; DOI:10.3945/ajcn.115.114306 · 6.77 Impact Factor
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    ABSTRACT: Dietary magnesium could modify the major stroke risk factors, high blood pressure (BP) and cholesterol, but has been understudied in both sexes in a single population. This study aimed to investigate if dietary magnesium intake was associated with BP, total cholesterol (TC) and incident stroke risk in an adult population. We conducted cross-sectional analyses in a case-cohort study of 4443, men and women aged 40-75, representative of 25,639 participants years of the EPIC (European Prospective Investigation into Cancer)-Norfolk cohort. The cohort included 928 stroke cases (42,556.5person years). Dietary data from 7day food diaries were analysed using multivariate regression to assess associations between quintiles or data-derived categories of dietary magnesium intake and BP, TC and stroke risk, adjusted for relevant confounders. We observed differences of -7mmHg systolic BP (P trend≤0.01) and -3.8mmHg diastolic BP (P trend=0.01) between extreme intakes of magnesium in men, a significant inverse association with TC was observed (P trend=0.02 men and 0.04 women). Compared to the bottom 10%, the top 30% of magnesium intake was associated with a 41% relative reduction in stroke risk (HR 0.59; 95% CI 0.38-0.93) in men. Lower dietary magnesium intake was associated with higher BP and stroke risk, which may have implications for primary prevention. Copyright © 2015. Published by Elsevier Ireland Ltd.
    International journal of cardiology 10/2015; 196. DOI:10.1016/j.ijcard.2015.05.166 · 4.04 Impact Factor
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    ABSTRACT: Background Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0462-9) contains supplementary material, which is available to authorized users.
    BMC Medicine 09/2015; 13(1). DOI:10.1186/s12916-015-0462-9 · 7.25 Impact Factor
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    ABSTRACT: Objectives: There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although findings from epidemiological studies are inconsistent. We investigated whether the risk is dependent on the age at which PA is measured and if independent of body mass index (BMI). Methods: A total of 23,639 participants, aged 40 to 74 years, were recruited into the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study between 1993 and 1997 and completed validated questionnaires on PA. The cohort was monitored for pancreatic cancer development, and hazard ratios (HRs) were estimated and adjusted for covariates. Results: Within 17 years, 88 participants developed pancreatic cancer (55% female). There was no association between PA and risk in the cohort (HR trend, 1.06; 95% confidence interval [CI], 0.86-1.29). However, in participants younger than 60 years, higher PA was associated with decreased risk (highest vs lowest category HR, 0.27; 95% CI, 0.07-0.99). Higher PA was not inversely associated when older than 60 years (HR trend, 1.23; 95% CI, 0.96-1.57). Including BMI in all models produced similar estimates. Conclusions: The reasons why PA in younger, but not older, people may prevent pancreatic cancer need to be investigated. Physical activity may operate through mechanisms independent of BMI. If this association is causal, 1 in 6 cases might be prevented by encouraging more PA.
    Pancreas 09/2015; DOI:10.1097/MPA.0000000000000494 · 2.96 Impact Factor
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    Neil M Davies · Tom R Gaunt · Sarah J Lewis · Jeff Holly · Jenny L Donovan · Freddie C Hamdy · John P Kemp · Rosalind Eeles · Doug Easton · Zsofia Kote-Jarai · [...] · Trina Yeadon · Joana Santos · Carmen Jeronimo · Paula Paulo · Pedro Pinto · Rui Henrique · Sofia Maia · Agnieszka Michael · Andrzej Kierzek · Huihai Wu ·
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    ABSTRACT: Background: Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods: We conducted a case-control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man's number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results: The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions: We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.
    Cancer Causes and Control 09/2015; 26(11). DOI:10.1007/s10552-015-0654-9 · 2.74 Impact Factor
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    ABSTRACT: Acrylamide, classified in 1994 by IARC as 'probably carcinogenic to humans', was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI <25 vs ≥25 kg/m(2) , alcohol drinkers vs never drinkers, oral contraceptive users vs non-users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type-I EC risk in 768 non-smoking postmenopausal women from the EPIC cohort. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 09/2015; DOI:10.1002/ijc.29853 · 5.09 Impact Factor
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    ABSTRACT: Background There is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22–23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers. Discussion Here we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function. Summary We present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological studies of human ageing, in health surveys of older people and as outcomes in intervention studies that aim to promote healthy ageing. Further, the inclusion of the same common panel of measures of healthy ageing in diverse study designs and populations may enhance the value of those studies by allowing the harmonisation of surrogate endpoints or outcome measures, thus facilitating less equivocal comparisons between studies and the pooling of data across studies. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0470-9) contains supplementary material, which is available to authorized users.
    BMC Medicine 09/2015; 13(1). DOI:10.1186/s12916-015-0470-9 · 7.25 Impact Factor
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    ABSTRACT: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10-14), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10-11; ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10-11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
    Nature 09/2015; 526(7571). DOI:10.1038/nature14878 · 41.46 Impact Factor
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    ABSTRACT: The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to assess the association between the American Heart Association-defined health metrics and the risk of cardiovascular events in the EPIC-Norfolk prospective study. Prospective cohort study. An overall cardiovascular health score was calculated based on the number of health metrics including ideal, intermediate or poor. Cox proportional hazards models were used to describe the association of the seven metrics separately and the overall health score with risk of coronary heart disease, stroke and cardiovascular disease. A total of 10,043 participants was included in the analysis (follow-up 1993-2008). For all individual health metrics a more ideal status was associated with a lower risk of cardiovascular events. As for the overall cardiovascular health score, those in the highest (i.e. healthiest) category (score 12-14) had an adjusted hazard ratio for coronary heart disease of 0.07 (95% confidence interval (CI) 0.02-0.29, P < 0.001), for stroke of 0.16 (95% CI 0.02-1.37, P = 0.09) and for cardiovascular disease of 0.07 (95% CI 0.02-0.23, P < 0.001), compared to people in the lowest (i.e. unhealthiest) category (score 0-2). The overall cardiovascular health score was strongly and inversely associated with risk of coronary heart disease, stroke and cardiovascular disease. Our data suggest that even small improvements in modifiable risk factors may lead to substantial reductions in the risks of cardiovascular events. © The European Society of Cardiology 2015.
    09/2015; DOI:10.1177/2047487315602015
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    ABSTRACT: Background: Results from several cohort and case–control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered.
    British Journal of Cancer 08/2015; 113(5):840-7. DOI:10.1038/bjc.2015.280 · 4.84 Impact Factor
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    ABSTRACT: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults. This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders. Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant. We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.
    European Journal of Nutrition 08/2015; DOI:10.1007/s00394-015-1023-x · 3.47 Impact Factor
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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.
    Cancer Epidemiology Biomarkers & Prevention 08/2015; DOI:10.1158/1055-9965.EPI-15-0543 · 4.13 Impact Factor

Publication Stats

30k Citations
5,677.67 Total Impact Points


  • 2015
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 1997-2015
    • University of Cambridge
      • • Department of Public Health and Primary Care
      • • Cambridge Institute of Public Health
      Cambridge, England, United Kingdom
  • 2014
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Berlín, Berlin, Germany
  • 2005-2014
    • Epic
      Verona, Wisconsin, United States
  • 2013
    • MRC Mitochondrial Biology Unit
      Cambridge, England, United Kingdom
  • 2012
    • Umeå University
      • Department of Clinical Sciences
      Umeå, Västerbotten, Sweden
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
    • Sapienza University of Rome
      Roma, Latium, Italy
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2008-2011
    • University of Oxford
      • Cancer Epidemiology Unit
      Oxford, ENG, United Kingdom
  • 2010
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2009
    • Cambridge Health Alliance
      Cambridge, Massachusetts, United States
  • 2004-2007
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Academic Medical Center
      • • Department of Vascular Medicine
      Amsterdam, North Holland, Netherlands
  • 2006
    • Universitetet i Tromsø
      • Department of Community Medicine
      Tromsø, Troms Fylke, Norway
  • 2003
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom