Kay-Tee Khaw

University of Cambridge, Cambridge, England, United Kingdom

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Publications (739)5751.44 Total impact

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    ABSTRACT: Background: Social inequalities in adult smoking and excessive alcohol intake may be associated with exposure to multiple childhood social risk factors across different domains of risk within the household. Methods: We used data from a cross-sectional cohort study of adults (40-75 years) in 1993-97 living in England (N = 19466) to examine the association between clusters of childhood social risks across different domains with adult smoking and excessive alcohol use. Participants reported exposure to six childhood social risk factors, current smoking behaviour and alcohol intake. Factor analysis was used to identify domains of social risk. We created a childhood cumulative domain social risk score (range 0-2) from summing the total number of domains. Results: Factor analysis identified two domains of childhood social risk within the household: maladaptive family functioning (parental unemployment, substance misuse, physical abuse) and parental separation experiences : maternal separation, divorce, being sent away from home). Compared to those children with risk exposure in no single domain, children with risk exposure in both domains (i.e. maladaptive family functioning, parental separation experiences) had a higher prevalence of adult smoking [men: Prevalence ratio (PR) = 1.74, 95% confidence intervals (CI): 1.35-2.26; women: PR = 1.71 95% CI: 1.34-2.18]. There was a trend association between the number of childhood social risk domains and adult smoking (both sexes: P < 0.001) and excessive alcohol use (men: P <0.008). Conclusions: Further work is needed to understand if addressing cumulative risk exposure to maladaptive family functioning and parental separation experiences can reduce social inequalities in adult smoking and excessive alcohol intake.
    No preview · Article · Feb 2016 · The European Journal of Public Health
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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: Variable agreement exists between different Lp(a) measurement methods, but their clinical relevance remains unclear. The predictive value of Lp(a) measured by two different assays (Randox and UCSD) was determined in 623 CAD cases and 948 controls in a case-control study within the EPIC-Norfolk prospective population study. Participants were divided into sex-specific quintiles, and by Lp(a) <50 versus >50 mg/dL, which represents the 80th percentile in northern European subjects.Randox and UCSD Lp(a) levels were strongly correlated, with Spearman correlation coefficients for men, women and sexes combined were 0.905, 0.915 and 0.909, respectively (p<0.001 for each).The >80th percentile cut-off values, however, were 36 mg/dL and 24 mg/dL for the Randox and UCSD assays, respectively. Despite this, Lp(a) levels were significantly associated with CAD risk, with odds ratios of 2.18 (1.58-3.01) and 2.35 (1.70-3.26) for people in the top versus bottom Lp(a) quintile for the Randox and UCSD assays, respectively. This study demonstrates that CAD risk is present at lower Lp(a) levels than the currently suggested optimal Lp(a) level of <50 mg/dL. Appropriate thresholds may need to be population and assay specific until Lp(a) assays are standardized and Lp(a) thresholds are evaluated broadly across all populations at risk for CVD and aortic stenosis.
    Preview · Article · Jan 2016 · The Journal of Lipid Research
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    ABSTRACT: We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association.
    No preview · Article · Jan 2016
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    ABSTRACT: Background: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and findings: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
    Preview · Article · Jan 2016 · PLoS ONE
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    ABSTRACT: Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case–control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10−3 were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43–2.24; P interaction = 1.2 × 10−4) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
    No preview · Article · Jan 2016 · Breast Cancer Research and Treatment

  • No preview · Article · Jan 2016 · American Journal of Clinical Nutrition
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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
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    ABSTRACT: Aims: Particular atherosclerotic risk factors may differ in their association with atherosclerosis across vascular territories. Few studies have compared the associations between multiple risk factors and cardiovascular disease (CVD) manifestations in one population. We studied the strength of the associations between traditional risk factors including coronary artery disease (CAD), ischaemic and haemorrhagic stroke, abdominal aortic aneurysms (AAAs), and peripheral arterial disease (PAD). Methods and results: This analysis included 21 798 participants of the EPIC-Norfolk population study, without previous CVD. Events were defined as hospitalization or mortality, coded using ICD-10. The associations between the risk factors, such as low-density lipoprotein cholesterol, systolic blood pressure (SBP), and smoking, and the various CVD manifestations were compared using competing risk analyses. During 12.1 years, 3087 CVD events were recorded. The associations significantly differed across CVD manifestations. Low-density lipoprotein cholesterol was strongly associated with CAD [adjusted hazard rate (aHR) highest vs. lowest quartile 1.63, 95% CI 1.44-1.86]. Systolic blood pressure was a strong risk factor for PAD (aHR highest vs. lowest quartile 2.95, 95% CI 1.78-4.89) and ischaemic stroke (aHR highest vs. lowest quartile 2.48, 95% CI 1.55-3.97), but not for AAA. Smoking was strongly associated with incident AAA (aHR current vs. never 7.66, 95% CI 4.50-13.04) and PAD (aHR current vs. never 4.66, 95% CI 3.29-6.61), but not with haemorrhagic stroke. Conclusion: The heterogeneity in the risk factor-CVD associations supports the concept of pathophysiological differences between atherosclerotic CVD manifestations and could have implications for CVD prevention.
    No preview · Article · Dec 2015 · European Heart Journal
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    ABSTRACT: Objective and background: Anemia and thyroid dysfunction are common and often co-occur. Current guidelines recommend the assessment of thyroid function in the work-up of anemia, although evidence on this association is scarce. Patients and methods: In the "European Prospective Investigation of Cancer" (EPIC)-Norfolk population-based cohort, we aimed to examine the prevalence and type of anemia (defined as hemoglobin <13 g/dl for men and <12 g/dl for women) according to different thyroid function groups. Results: The mean age of the 8791 participants was 59.4 (SD 9.1) years and 55.2% were women. Thyroid dysfunction was present in 437 (5.0%) and anemia in 517 (5.9%) participants. After excluding 121 participants with three most common causes of anemia (chronic kidney disease, inflammation, iron deficiency), anemia was found in 4.7% of euthyroid participants. Compared with the euthyroid group, the prevalence of anemia was significantly higher in overt hyperthyroidism (14.6%, P < .01), higher with borderline significance in overt hypothyroidism (7.7%, P = .05) and not increased in subclinical thyroid dysfunction (5.0% in subclinical hypothyroidism, 3.3% in subclinical hyperthyroidism). Anemia associated with thyroid dysfunction was mainly normocytic (94.0%), and rarely macrocytic (6.0%). Conclusion: The prevalence of anemia was higher in overt hyperthyroidism, but not increased in subclinical thyroid dysfunction. Systematic measurement of thyroid-stimulating hormone in anemic patients is likely to be useful only after excluding common causes of anemia.
    No preview · Article · Dec 2015 · Clinical Endocrinology
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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: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk. Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort. Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs. Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41). Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.
    No preview · Article · Nov 2015 · American Journal of Clinical Nutrition
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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.
    Full-text · Article · Nov 2015 · Endocrine Related Cancer
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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.
    Preview · Article · Nov 2015 · American Journal of Clinical Nutrition
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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.
    Full-text · Article · Nov 2015 · British Journal of Cancer
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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.
    No preview · Article · Nov 2015 · American Journal of Clinical Nutrition
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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.
    No preview · Article · Nov 2015 · Breast Cancer Research and Treatment
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    ABSTRACT: Generalised anxiety disorder, one of the most common anxiety disorders in the general population, has been associated with disability, impairment, and high health service use. Whereas the effect of individual-level socioeconomic status on generalised anxiety disorder has been well researched, an understanding of the links between area-level (contextual) measures of deprivation and this disorder is less clear. Deprivation has been shown to be a determinant of general mental distress, depression, and a range of physical health outcomes; however, its association with generalised anxiety disorder is unknown. We aimed to examine whether area-level deprivation is associated with generalised anxiety disorder over and above individual-level circumstances in a British community cohort.
    Full-text · Article · Nov 2015 · The Lancet
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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.
    No preview · Article · Oct 2015 · Medicine and science in sports and exercise
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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

Publication Stats

33k Citations
5,751.44 Total Impact Points


  • 1997-2016
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
  • 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
  • 2011
    • University of Oxford
      • Cancer Epidemiology Unit
      Oxford, ENG, United Kingdom
  • 2010
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
    • Cancer Research UK Cambridge Institute
      Cambridge, England, United Kingdom
  • 2009
    • Cambridge Health Alliance
      Cambridge, Massachusetts, United States
  • 2007
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2006
    • Universitetet i Tromsø
      • Department of Community Medicine
      Tromsø, Troms Fylke, Norway
  • 2005-2006
    • Epic
      Verona, Wisconsin, United States
  • 2004
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Vascular Medicine
      Amsterdamo, North Holland, Netherlands
  • 2003
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom