Kay-Tee Khaw

The University of Warwick, Coventry, England, United Kingdom

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Publications (680)4986.9 Total impact

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    ABSTRACT: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.
    JAMA Internal Medicine 04/2015; DOI:10.1001/jamainternmed.2015.0930 · 13.25 Impact Factor
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    ABSTRACT: Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute non-dense area adjusted for study, age and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1) and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all p <10-5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and non-dense areas, and between rs17356907 (NTN4) and adjusted absolute non-dense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiological pathways implicated in how mammographic density predicts breast cancer risk. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 04/2015; DOI:10.1158/0008-5472.CAN-14-2012 · 9.28 Impact Factor
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    ABSTRACT: To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data (IPD) on thyroid function and stroke outcome. Euthyroidism was defined as thyrotropin (TSH) levels 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH levels 4.5-19.9 mIU/L with normal thyroxin levels. Data Extraction and Synthesis We collected IPD on 47,573 adults (3451 subclinical hypothyroidism) from 17 cohorts, followed-up 1972-2014 (489,192 person-years). Age- and sex-adjusted pooled hazard ratio (HR) for participants with subclinical hypothyroidism compared to euthyroidism was 1.05 (95% CI, 0.91-1.21) for stroke events (combined fatal and non-fatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years (HR 1.00, 95% CI, 0.86-1.18) or ≥80 years (HR 1.31, 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.
    The Journal of Clinical Endocrinology and Metabolism 04/2015; DOI:10.1210/jc.2015-1438 · 6.31 Impact Factor
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    ABSTRACT: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist <80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 04/2015; DOI:10.1158/1055-9965.EPI-14-1279-T · 4.32 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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    ABSTRACT: Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), Ptrend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to ≥4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07). Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
    Breast Cancer Research 03/2015; 17(1). DOI:10.1186/s13058-015-0563-6 · 5.33 Impact Factor
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    ABSTRACT: Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. To investigate associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Data was available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034mg/d (range: 0-8531mg/d) for men and 970mg/d (0-6695mg/d) for women, median intake of flavan-3-ol monomers was 233mg/d (0-3248mg/d) for men and 217 (0-2712mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow up, there were 8463 cardio-vascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk. Copyright © 2015. Published by Elsevier Inc.
    Free Radical Biology and Medicine 03/2015; 31. DOI:10.1016/j.freeradbiomed.2015.03.005 · 5.71 Impact Factor
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    ABSTRACT: Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity (e.g. body mass index [BMI]≥40 kg/m(2)), but their contribution to common obesity (BMI≥30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331,175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CI) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR=1.15, 95% CI 1.06-1.24, P=6.08x10(-6)) and rs6234/rs6235 (OR=1.07, 95% CI 1.04-1.10, P=3.00x10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta=0.03, 95% CI 0.00-0.07; P=0.047) and rs6234/rs6235 (beta=0.02, 95% CI 0.00-0.03; P=5.57x10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Molecular Genetics 03/2015; DOI:10.1093/hmg/ddv097 · 6.68 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.
    Nature Genetics 03/2015; DOI:10.1038/ng.3242 · 29.65 Impact Factor
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    ABSTRACT: Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 03/2015; 96(3):487-97. DOI:10.1016/j.ajhg.2015.01.011 · 10.99 Impact Factor
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    ABSTRACT: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
    American Journal of Clinical Nutrition 03/2015; 101(3):613-21. DOI:10.3945/ajcn.114.100065 · 6.92 Impact Factor
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    ABSTRACT: Dietary recommendations to promote health include fresh, frozen and tinned fruit, but few studies have examined the health benefits of tinned fruit. We therefore studied the association between tinned fruit consumption and mortality. We followed up participants from three prospective cohorts in the United Kingdom: 22,421 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort (1993-2012), 52,625 participants from the EPIC-Oxford cohort (1993-2012), and 7440 participants from the Whitehall II cohort (1991-2012), all reporting no history of heart attack, stroke, or cancer when entering these studies. We estimated the association between frequency of tinned fruit consumption and all cause mortality (primary outcome measure) using Cox regression models within each cohort, and pooled hazard ratios across cohorts using random-effects meta-analysis. Tinned fruit consumption was assessed with validated food frequency questionnaires including specific questions about tinned fruit. During 1,305,330 person years of follow-up, 8857 deaths occurred. After adjustment for lifestyle factors and risk markers the pooled hazard ratios (95% confidence interval) of all cause mortality compared with the reference group of tinned fruit consumption less often than one serving per month were: 1.05 (0.99, 1.12) for one to three servings per month, 1.10 (1.03, 1.18) for one serving per week, and 1.13 (1.04, 1.23) for two or more servings per week. Analysis of cause-specific mortality showed that tinned fruit consumption was associated with mortality from cardiovascular causes and from non-cardiovascular, non-cancer causes. In a pooled analysis of three prospective cohorts from the United Kingdom self-reported tinned fruit consumption in the 1990s was weakly but positively associated with mortality during long-term follow-up. These findings raise questions about the evidence underlying dietary recommendations to promote tinned fruit consumption as part of a healthy diet.
    PLoS ONE 02/2015; 10(2):e0117796. DOI:10.1371/journal.pone.0117796 · 3.53 Impact Factor
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    ABSTRACT: To study the association between sleep duration and stroke incidence in a British population and to synthesize our findings with published results through a meta-analysis. The prospective study included 9,692 stroke-free participants aged 42-81 years from the European Prospective Investigation into Cancer-Norfolk cohort. Participants reported sleep duration in 1998-2000 and 2002-2004, and all stroke cases were recorded until March 31, 2009. For the meta-analysis, we searched Ovid Medline, EMBASE, and the Cochrane Library for prospective studies published until May 2014, and pooled effect estimates using a weighted random-effect model. After 9.5 years of follow-up, 346 cases of stroke occurred. Long sleep was significantly associated with an increased risk of stroke (hazard ratio [HR] = 1.46 [95% confidence interval (CI) 1.08, 1.98]) after adjustment for all covariates. The association remained robust among those without preexisting diseases and those who reported sleeping well. The association for short sleep was smaller (and not statistically significant) (HR = 1.18 [95% CI 0.91, 1.53]). There was a higher stroke risk among those who reported persistently long sleep or a substantial increase in sleep duration over time, compared to those reporting persistently average sleep. These were compatible with the pooled HRs from an updated meta-analysis, which were 1.15 (1.07, 1.24) and 1.45 (1.30, 1.62) for short and long sleep duration, respectively. This prospective study and meta-analysis identified prolonged sleep as a potentially useful marker of increased future stroke risk in an apparently healthy aging population. © 2015 American Academy of Neurology.
    Neurology 02/2015; DOI:10.1212/WNL.0000000000001371 · 8.30 Impact Factor
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    ABSTRACT: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. The European Prospective Investigation into Cancer and Nutrition (EPIC). Women (n 334 850) from the EPIC study. The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01). TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.
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    ABSTRACT: The objective of the present study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Prospective cohort study. EPIC-Norfolk in the UK, recruitment between 1993 and 1997. Men and women (n 1734) aged 39-77 years. Sucrose intake was assessed using 7 d diet diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as a biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI>25·0 kg/m2 after three years of follow-up. After three years of follow-up, mean BMI was 26·8 kg/m2. Self-reported sucrose intake was significantly positively associated with the biomarker. Associations between the biomarker and BMI were positive (β=0·25; 95 % CI 0·08, 0·43), while they were inverse when using self-reported dietary data (β=-1·40; 95 % CI -1·81, -0·99). The age- and sex-adjusted OR for BMI>25·0 kg/m2 in participants in the fifth v. first quintile was 1·54 (95 % CI 1·12, 2·12; P trend=0·003) when using biomarker and 0·56 (95 % CI 0·40, 0·77; P trend<0·001) with self-reported dietary data. Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with BMI. Future studies should consider the use of objective biomarkers of sucrose intake.
    Public Health Nutrition 02/2015; DOI:10.1017/S1368980015000300 · 2.48 Impact Factor
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    ABSTRACT: Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images. Optic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83-88% across both trials and study designs, however the specificity was poor, ranging between 35-43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62-0.66) and in trial 2 it was 0.63(0.61-0.65). There were no significant differences between study design or trials conducted. Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.
    PLoS ONE 02/2015; 10(2):e0117401. DOI:10.1371/journal.pone.0117401 · 3.53 Impact Factor
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    ABSTRACT: Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies (GWAS) have identified 100 risk variants for prostate cancer, which can explain ~33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3' UTR of genes predicted to affect miRNA binding (miRSNPs) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (p<2.3x10-5) with risk of prostate cancer, 10 of which were within the 7 genes previously not mapped by GWASs. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele whilst miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Copyright © 2015, American Association for Cancer Research.
    Cancer Discovery 02/2015; DOI:10.1158/2159-8290.CD-14-1057 · 15.93 Impact Factor
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    ABSTRACT: To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). Cross sectional study nested within a longitudinal cohort study. Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7-13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36-0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
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    ABSTRACT: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.
    PLoS ONE 02/2015; 10(2):e0118206. DOI:10.1371/journal.pone.0118206 · 3.53 Impact Factor

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24k Citations
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Institutions

  • 2015
    • The University of Warwick
      • Division of Mental Health and Wellbeing
      Coventry, England, United Kingdom
  • 2012–2015
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
    • University of Texas MD Anderson Cancer Center
      • Division of Cancer Prevention & Population Sciences
      Houston, TX, United States
    • Otto-von-Guericke-Universität Magdeburg
      • Institute for Clinical Chemistry and Pathobiochemistry
      Magdeburg, Saxony-Anhalt, Germany
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
    • Brown University
      • Division of Biology and Medicine
      Providence, RI, United States
    • Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte
      Torino, Piedmont, Italy
    • Aarhus University Hospital
      • Department of Cardiology
      Århus, Central Jutland, Denmark
    • University of Cologne
      • Heart Center
      Köln, North Rhine-Westphalia, Germany
  • 1997–2015
    • University of Cambridge
      • • Department of Public Health and Primary Care
      • • Cambridge Institute of Public Health
      Cambridge, England, United Kingdom
  • 2014
    • Centre d'Immunologie de Marseille-Luminy
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2011–2014
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
    • INRAN - Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione
      Roma, Latium, Italy
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
    • University of São Paulo
      • Faculdade de Saúde Pública (FSP) (São Paulo)
      Ribeirão Preto, Estado de Sao Paulo, Brazil
    • University of Oxford
      • Nuffield Department of Clinical Medicine
      Oxford, ENG, United Kingdom
  • 2006–2014
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Berlín, Berlin, Germany
    • Universitetet i Tromsø
      • Department of Community Medicine
      Tromsø, Troms Fylke, Norway
  • 2013
    • University of Naples Federico II
      • Department of Clinical Medicine and Surgery
      Napoli, Campania, Italy
    • Universitätsklinikum Freiburg
      • Center for Chronic Immunodeficiency (CCI)
      Freiburg, Lower Saxony, Germany
    • Moorfields Eye Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2011–2013
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2010–2013
    • University College London
      • • Faculty of Population Health Sciences
      • • Department of Epidemiology and Public Health
      • • Centre for Cardiovascular Biology and Medicine
      Londinium, England, United Kingdom
    • Norfolk and Norwich University Hospitals NHS Foundation Trust
      Norwich, England, United Kingdom
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
    • Institut universitaire de cardiologie et de pneumologie de Québec
      Québec, Quebec, Canada
    • Broad Institute of MIT and Harvard
      • Program in Medical and Population Genetics
      Cambridge, Massachusetts, United States
    • Universidade Federal de Ouro Preto
      • Department of Social and Clinical Nutrition(DENCS)
      Ouro Preto, Minas Gerais, Brazil
  • 2008–2013
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
    • Umeå University
      • • Department of Medical Biosciences
      • • Department of Surgical and Perioperative Sciences
      Umeå, Västerbotten, Sweden
  • 2006–2013
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2005–2013
    • University Medical Center Utrecht
      • • Department of Gastroenterology and Hepatology
      • • Julius Center for Health Sciences and Primary Care
      Utrecht, Utrecht, Netherlands
  • 2004–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Vascular Medicine
      • • Academic Medical Center
      Amsterdam, North Holland, Netherlands
  • 2011–2012
    • Aarhus University
      • • Department of Public Health
      • • Department of Clinical Epidemiology
      Aars, Region North Jutland, Denmark
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • School of Public Health
      London, ENG, United Kingdom
  • 2007–2012
    • Catalan Institute of Oncology
      • Cancer Epidemiology Research Programme (PREC)
      Badalona, Catalonia, Spain
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • Laval University
      • Department of Social and Preventive Medicine
      Quebec City, Quebec, Canada
  • 2005–2012
    • International Agency for Research on Cancer
      • Nutritional Epidemiology Group
      Lyons, Rhône-Alpes, France
  • 2009–2011
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
    • University of East Anglia
      • • Norwich Medical School
      • • Health and Social Sciences Research Institute
      Norwich, England, United Kingdom
    • Cambridge Health Alliance
      Cambridge, Massachusetts, United States
    • MRC Mitochondrial Biology Unit
      Cambridge, England, United Kingdom
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo County, Norway
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
  • 2006–2007
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 2004–2006
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2003
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom