Habitual chocolate consumption and the risk of incident heart failure among healthy men and women.

BACKGROUND: 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. METHODS AND RESULTS: We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). CONCLUSIONS: Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure.

Long-term mortality of hospitalized pneumonia in the EPIC-Norfolk cohort.

Little is known about cause-specific long-term mortality beyond 30 days in pneumonia. We aimed to compare the mortality of patients with hospitalized pneumonia compared to age- and sex-matched controls beyond 30 days. Participants were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study. Hospitalized pneumonia cases were identified from record linkage (ICD-10: J12-J18). For this study we excluded people with hospitalized pneumonia who died within 30 days. Each case identified was matched to four controls and followed up until the end June 2012 (total 15 074 person-years, mean 6·1 years, range 0·08-15·2 years). Cox regression models were constructed to examine the all-cause, respiratory and cardiovascular mortality using date of pneumonia onset as baseline with binary pneumonia status as exposure. A total of 2465 men and women (503 cases, 1962 controls) [mean age (s.d.) 64·5 (8·3) years] were included in the study. Between a 30-day to 1-year period, hazard ratios (HRs) of all-cause and cardiovascular mortality were 7·3 [95% confidence interval (CI) 5·4-9·9] and 5·9 (95% CI 3·5-9·7), respectively (with very few respiratory deaths within the same period) in cases compared to controls after adjusting for age, sex, asthma, smoking status, pack years, systolic and diastolic blood pressure, diabetes, physical activity, waist-to-hip ratio, prevalent cardiovascular and respiratory diseases. All outcomes assessed also showed increased risk of death in cases compared to controls after 1 year; respiratory cause of death being the most significant during that period (HR 16·4, 95% CI 8·9-30·1). Hospitalized pneumonia was associated with increased all-cause and specific-cause mortality beyond 30 days.

The association between a biomarker score for fruit and vegetable intake and incident type 2 diabetes: the EPIC-Norfolk study.

BACKGROUND/OBJECTIVES: Biomarkers for a mixed fruit and vegetable (FV) diet are needed to provide a better understanding of the association between FV intake and type 2 diabetes. We aimed to examine the prospective association between a composite score comprised of three biomarkers of FV intake in free-living populations and incident diabetes. SUBJECTS/METHODS: A total of 318 incident diabetes cases and 926 controls from the EPIC (European Prospective Investigation of Cancer)-Norfolk study aged 40-79 years at baseline (1993-1997), completed 7-day prospective food diary and had plasma vitamin C and carotenoid measures. A composite biomarker score (CB-score) comprising the sum of plasma vitamin C, beta-carotene and lutein was derived. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident diabetes were estimated using multivariable logistic regression. RESULTS: A strong inverse association was found between the CB-score and incident diabetes. The ORs (95% CI) of diabetes comparing quartiles Q2, Q3 and Q4 of the CB-score with Q1 (reference category) were 0.70 (0.49, 1.00), 0.34 (0.23, 0.52) and 0.19 (0.12, 0.32), respectively, and 0.49 (0.40, 0.58) per s.d. change in CB-score in a model adjusted for demographic and lifestyle factors. The association was marginally attenuated after additionally adjusting for body mass index and waist circumference (0.60 (0.49 and 0.74) per s.d. change in CB-score). CONCLUSIONS: A combination of biomarkers representing the intake of a mixed FV diet was strongly inversely associated with incident diabetes. These findings provide further support for measuring dietary biomarkers in studies of diet-disease associations and highlight the importance of consuming FV for the prevention of diabetes.

Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort.

BACKGROUND: Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations. METHODS: Seven-day diet diaries and blood samples were taken from two subsets of the European Prospective Investigation into Cancer (EPIC-Norfolk) cohort (age range 39-79 years; n = 1400 for vitamin D; n = 6656 for remaining nutrients). TNI was calculated for the subgroups: nonsupplement users, those consuming the nutrient in supplement form and those consuming a supplement without this nutrient. RESULTS: CLO-related nutrients were supplemented by 15%-33%, which approximately doubled median intakes. Almost everyone in the supplement + vitamin A group reached the estimated average requirement; however, guideline levels were likely to be exceeded. Partial correlations between intake of vitamins A and D and biomarkers were low and modestly strengthened by the inclusion of supplement sources (correlation = 0.01-0.13). Correlations between biomarker and TNI of vitamin E and EPA+DHA were in the range 0.40-0.46; however, vitamin E exceeding food intake resulted in attenuated coefficients. Linear associations between food or TNI EPA+DHA and plasma were weak but consistent across subgroups. CONCLUSIONS: CLO-related nutrients contribute substantially to nutrient intake, with a risk of over-consumption. Apart from EPA+DHA, biomarker data suggest that CLO-related nutrients in supplements are not linearly associated with vitamin status.

Self-reported and measured anthropometric data and risk of colorectal cancer in the EPIC-Norfolk study.

BACKGROUND: Epidemiological studies have shown inconsistent results for the association between body size and colorectal cancer (CRC) risk. Inconsistencies may be because of the reliance on self-reported measures of body size. OBJECTIVE: We examined the association of self-reported and directly assessed anthropometric data (body height, weight, body mass index (BMI), waist, hip, waist-to-hip ratio (WHR) and chest circumference) with CRC risk in the EPIC-Norfolk study. DESIGN: A total of 20,608 participants with complete self-reported and measured height and weight and without any history of cancer were followed up an average of 11 years, during which 357 incident CRC cases were recorded. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: After adjustment for confounders, HRs among women in the highest quintile of the body size measure relative to the lowest quintile showed that measured height (HR=1.98, 95% CI=1.19-3.28, P (trend)=0.009), measured waist circumference (HR=1.65, 95% CI=0.97-2.86, P (trend)=0.009) and measured WHR (HR=2.07, 95% CI=1.17-3.67, P (trend)=0.001) were associated with increased CRC risk. Associations using corresponding self-reported measures were attenuated and not statistically significant. Conversely, the association of BMI with CRC risk in women was weaker using measured BMI (HR=1.57, 95% CI=0.91-2.73, P (trend)=0.05) compared with self-reported BMI (HR=1.97, 95% CI=1.18-3.30, P (trend)=0.02). In men no significantly increased CRC risk was observed with any of the anthropometric measures. CONCLUSIONS: Measured height, waist circumference and WHR were associated with CRC risk in women, whereas any significant associations with those measures were attenuated when self-reported data were used.

Body fat mass is a predictor of risk of osteoporotic fractures in women but not in men: a prospective population study.

OBJECTIVES: Obesity has generally been associated with higher bone density and lower fracture risk. However, weight-related indices of obesity may be related differently to health end-points, compared with fat-related indices (such as body fat distribution and fat mass), as they may capture different dimensions of obesity and the associated biological effects. The aim of this study was to examine the association between percentage body fat (%BF) and prospective risk of fracture. METHODS: The European Prospective Investigation into Cancer (EPIC) in Norfolk was a population-based prospective study. A total of 14 789 participants (6470 men, aged 42-82 years at baseline) were included. The main outcome measures were quantitative ultrasound of the heel and incident hip and any osteoporotic fractures. RESULTS: A total of 556 participants suffered a fracture (184 hip fractures) during 8.7 ± 0.8 years of follow-up. Risk of hip fracture decreased linearly with increasing %BF amongst women but not men. After adjustment for age, history of fracture, height, smoking, alcohol intake and heel broadband ultrasound attenuation (BUA), the hazard ratio (95% CI) for a 10% higher %BF on risk of hip fracture was 0.56 (0.39-0.79) in women and 0.92 (0.39-2.21) in men. The effect size in women was approximately equivalent to a difference of 5 years in age or 1 standard deviation (17 dB MHz(-1) ) increased BUA. A nonlinear negative association was also observed between %BF and risk of 'any type of fracture' amongst women but not men. CONCLUSIONS: The %BF appears to predict hip fracture risk in women with an effect size comparable to that of bone density as measured by heel ultrasound. This effect was not observed in men. Understanding the differences in relationships between different indices of obesity as well as sex differences may help to elucidate the metabolic and other underlying mechanisms involved in bone health and fracture risk.

Fibre intake in relation to serum total cholesterol levels and CHD risk: a comparison of dietary assessment methods.

BACKGROUND/OBJECTIVES: Prospective diet diaries may be more accurate than retrospective food frequency questionnaires (FFQ). The objective of this study was to compare FFQ and 7-day diet diary (7DD) measurements of fibre intake with the incidence of coronary heart disease (CHD). SUBJECTS/METHODS: We compared 7DD and FFQ fibre intake in a nested case-control study in a population of 25639 men and women aged 40-79 years, surveyed in 1993-97 and followed up until 2007. Among 2151 CHD cases and 5354 controls, FFQ and 7DD fibre intake (6 g/day) was examined in relation to serum total cholesterol and CHD using linear and logistic regression adjusted for age and additionally for body mass index, physical activity, smoking status, family history of CHD, social class, diabetes, alcohol, energy, saturated fat and use of lipid lowering medication, antihypertensive medication or aspirin. RESULTS: Age-adjusted serum total cholesterol was inversely associated with 7DD fibre among men and women, but with FFQ fibre among men only. In the multivariate analysis, associations with 7DD fibre were attenuated among men (regression coefficient -0.036 mmol/l, s.e. 0.021, P-value 0.087) and women (regression coefficient -0.069 mmol/l, s.e. 0.036, P-value 0.053), and were non-significant for FFQ fibre. Among men, age-adjusted CHD risk was inversely associated with 7DD fibre (odds ratio (OR) 0.84, 95% confidence interval (CI) 0.79-0.90), but not with FFQ fibre (OR 0.96, 95% CI 0.90-1.12). Among women, age-adjusted CHD risk was inversely associated with 7DD fibre (OR 0.83, 95% CI 0.75-0.93), and had a weaker inverse borderline-significant association with FFQ fibre (OR 0.93, 95% CI 0.87-1.01). Multivariate models yielded similar results. CONCLUSIONS: Inconsistencies in diet-CHD relationships in population studies may be associated with the use of different dietary assessment methods.

Individual and cumulative effect of type 2 diabetes genetic susceptibility variants on risk of coronary heart disease.

AIMS/HYPOTHESIS: Type 2 diabetes is a major risk factor for CHD. We hypothesised that diabetes genetic susceptibility variants might be associated with increased CHD risk. METHODS: We examined the individual and cumulative effect of 38 common genetic variants previously reported to be associated with type 2 diabetes on risk of incident CHD in 20,467 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk Study who had been free of CHD at baseline. RESULTS: During a mean follow-up of 10.7 years, 2,190 participants had a CHD event. Two individual variants next to the TSPAN8 (HR 1.07, 95% CI 1.00-1.14) and the CDKN2A/B region (1.11, 1.04-1.17) were significantly associated with increased CHD risk. A genetic score based on the 38 diabetes variants was significantly associated with an increased risk of CHD (1.08, 1.01-1.14 per score tertile). Adjustment for prevalent and incident diabetes attenuated the association of the TSPAN8 variant (1.06, 0.99-1.13) and the genetic score (1.05, 0.99-1.12 per score tertile) with CHD risk, but not that of the CDKN2A/B variant (1.11, 1.05-1.18). Addition of the genetic score did not improve risk discrimination based on clinical risk factors. CONCLUSIONS/INTERPRETATION: The increased risk of CHD observed with genetic susceptibility to type 2 diabetes was at least partly mediated by its diabetes-predisposing effect and was not useful for clinical risk discrimination. The potential role of pathways associated with the variant CDKN2A/B in linking diabetes and CHD needs further exploration.

Genetic predisposition to obesity leads to increased risk of type 2 diabetes.

AIMS/HYPOTHESIS: Obesity is a major risk factor for type 2 diabetes. Recent genome-wide association (GWA) studies have identified multiple loci robustly associated with BMI and risk of obesity. However, information on their associations with type 2 diabetes is limited. Such information could help increase our understanding of the link between obesity and type 2 diabetes. We examined the associations of 12 obesity susceptibility loci, individually and in combination, with risk of type 2 diabetes in the population-based European Prospective Investigation of Cancer (EPIC) Norfolk cohort. METHODS: We genotyped 12 SNPs, identified by GWA studies of BMI, in 20,428 individuals (aged 39-79 years at baseline) with an average follow-up of 12.9 years, during which 729 individuals developed type 2 diabetes. A genetic predisposition score was calculated by adding the BMI-increasing alleles across the 12 SNPs. Associations with incidence of type 2 diabetes were examined by logistic regression models. RESULTS: Of the 12 SNPs, eight showed a trend with increased risk of type 2 diabetes, consistent with their BMI-increasing effects. Each additional BMI-increasing allele in the genetic predisposition score was associated with a 4% increased odds of developing type 2 diabetes (OR 1.041, 95% CI 1.005-1.078; p = 0.02). Adjustment for BMI completely abolished the association with incident type 2 diabetes (OR 1.003, 95% CI 0.967-1.039; p = 0.89). CONCLUSIONS/INTERPRETATION: The genetic predisposition to obesity leads to increased risk of developing type 2 diabetes, which is completely mediated by its obesity-predisposing effect.

Effects of body size and sociodemographic characteristics on differences between self-reported and measured anthropometric data in middle-aged men and women: the EPIC-Norfolk study.

BACKGROUND/OBJECTIVES: To investigate the effects of body size and sociodemographic characteristics on differences between self-reported (SR) and measured anthropometric data in men and women. SUBJECTS/METHODS: This study comprises 9933 men and 11,856 women aged 39-79 years at baseline survey (1993-1997) in the EPIC-Norfolk study (Norfolk arm of the European Investigation into Cancer and Nutrition Study). The effects of sex, measured height, weight, age group, educational level and social class on differences between SR and measured weight, height, body mass index (BMI), waist, hip and waist-to-hip ratio (WHR) were examined. RESULTS: There were systematic differences between SR and measured anthropometric measurements by sex, measured height, weight and sociodemographic characteristics. Height was overestimated in both sexes while weight, waist, hip, and consequently, BMI and WHR were underestimated. Being male, shorter, heavier, older, and having no educational qualifications and manual occupation were independently associated with overreporting of height, and underreporting of weight was associated independently with being female, shorter, heavier, younger age, and higher education level and social class. Underreporting of waist circumference was strongly associated with being female and higher measured waist circumference, while underreporting of hip circumference was associated with being male and higher measured hip circumference. Furthermore, there was substantial degree of misclassification of BMI and waist circumference categories for both general and central obesity associated with SR data. CONCLUSIONS: These findings suggest that errors in SR anthropometric data, especially waist and hip circumference are influenced by actual body size as well as sociodemographic characteristics. These systematic differences may influence associations between SR anthropometric measures and health outcomes in epidemiological studies.

Alcohol intake and risk of colorectal cancer: results from the UK Dietary Cohort Consortium.

BACKGROUND: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent. METHODS: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ). RESULTS: Compared with individuals in the lightest category of drinkers (>0-<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5-<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15-<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30-<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with >or=45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results. CONCLUSION: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium.

Factor VII, blood lipids and fat intake: gene-nutrient interaction and risk of coronary heart disease with the factor VII R353Q polymorphism.

BACKGROUND: The relation between dietary fat, blood lipids, plasma factor VII coagulant activity (FVIIc) and risk of coronary heart disease (CHD) according to the R353Q polymorphism in the factor VII gene was assessed. METHODS: Cross-sectional study of 15,073 individuals participating in the European Prospective Investigation of Cancer (EPIC) Norfolk, 7433 of which had FVIIc available. Nested case-control study of 985 CHD cases and 2009 matched controls. RESULTS: FVIIc was significantly associated with total fat intake in females, especially in the RR homozygotes (standardized beta=0.24; 95% confidence interval (95% CI) 0.08-0.40; P<0.01), but there were no associations with intakes of saturated, monounsaturated or polyunsaturated fatty acids according to genotype and no associations in males. FVIIc was significantly positively associated with total cholesterol (P<0.01) and with triacylglycerol (P<0.001) in both genders, with an interaction according to genotype for triacylglycerol in males: beta Q allele carriers 0.26 (95% CI 0.18-0.34), beta RR homozygotes 0.16 (95% CI 0.12-0.20) (Z interaction=-2.24; P<0.05). There was no effect of genotype on the odds ratio (OR) for incident CHD: OR 0.89 for Q allele carriers compared with RR homozygotes (95% CI 0.77-1.02) in 985 cases and 2009 matched controls. CONCLUSION: These results show a strong association between dietary fat intake and FVIIc in women, and between serum triacylglycerol and cholesterol and FVIIc levels in both genders. The R353Q genotype only marginally affected modulation of FVIIc by dietary fat. The association between triacylglycerol and FVIIc was significantly stronger in males carrying the Q allele than in those with the RR genotype.

Prospective association between emotional health and clinical evidence of Parkinson's disease.

BACKGROUND AND PURPOSE: Whilst disorders of emotion are commonly comorbid with Parkinson's disease (PD), evidence concerning their association with PD risk is limited. We investigate the prospective association between selected measures of emotional health and incident suspected PD. METHODS: 20,855 men and women, considered PD-free at baseline, completed a postal assessment of major depressive disorder (MDD), generalized anxiety disorder (GAD), psychological distress [defined by the five-item Mental Health Inventory (MHI-5)], and neuroticism. PD case ascertainment was based upon PD medication use, self-report questionnaires, hospital record discharge codes, and death certification, subsequently checked against general practitioner, hospital records and neurological service records. RESULTS: 175 suspected cases of incident PD were identified in 160,725 (median 7.9) person-years of follow-up (with 43 recorded in neurological service records). MDD lifetime history, GAD lifetime history, MHI-5 and neuroticism were all significantly associated with suspected PD following adjustment for age, sex, cigarette smoking, alcohol consumption, social class and education. CONCLUSIONS: This study supports an association between measures of emotional health, assessed prior to evidence of motor symptoms, and subsequent suspected PD diagnosis. However, we were unable to determine whether our measures of personality and emotional health represent genuine premorbid risk factors or early stages of PD. Long-term prospective healthy cohort studies are required to investigate the relationship between emotional health history and the evolution of the premotor and motor phases of PD.

Sense of coherence, lifestyle choices and mortality.

BACKGROUND: Based on data from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) study, we have previously shown a strong sense of coherence (SOC) to be associated with a reduced rate of all-cause mortality. OBJECTIVES: To investigate the extent to which the SOC mortality association can be explained by socioeconomic status and lifestyle choices. DESIGN AND SETTING: Prospective population-based cohort study. PARTICIPANTS: 18 287 study participants aged 41-80 years who reported no pre-existing chronic disease at baseline and who completed an assessment of SOC. RESULTS: Based on 1599 deaths during a mean follow-up of 8.3 years, a strong SOC was associated with a 20% reduced risk of all-cause mortality. Measures of lifestyle choice (cigarette smoking, physical activity, dietary intakes of fruit, vegetables and fibre) and socioeconomic status (social class and education) explained 23% of this association. CONCLUSIONS: The SOC concept embraces multiple sets of chronic disease risk factors that include lifestyle choices and those associated with socioeconomic status, and is a potential aid in understanding differences in health outcomes in similar individuals.

Psychological distress, major depressive disorder, and risk of stroke.

BACKGROUND: Studies have suggested that mood status is associated with an increased risk of stroke, though mostly based on measures of depression defined by symptoms alone rather than diagnostic criteria representative of clinically important distress and impairment. We investigated this association based upon a large population-based prospective cohort study. METHODS: Baseline assessment of major depressive disorder (MDD) and of mental health well-being (defined by the Mental Health Inventory, MHI-5) was completed by 20,627 stroke-free participants, aged 41 to 80 years, in the United Kingdom European Prospective Investigation into Cancer-Norfolk study. RESULTS: During 8.5 years of follow-up, 595 incident (fatal and nonfatal) stroke endpoints were recorded. Neither past year nor lifetime MDD was associated with stroke. A one SD decrease in MHI-5 scale score (representing greater emotional distress) was associated with an 11% increased risk of stroke after adjustment for age, sex, cigarette smoking, systolic blood pressure, cholesterol, obesity, preexisting myocardial infarction, diabetes, social class, education, hypertension treatment, family history of stroke, and antidepressant medication use (hazard ratio 1.11, 95% CI 1.00 to 1.22). This association was consistent for men and for women, for fatal and nonfatal stroke, and conformed to a dose-response relationship. CONCLUSIONS: Findings from this large prospective cohort study suggest that increased psychological distress is associated with elevated stroke risk. Episodic major depressive disorder was not associated with incident stroke in this study.

Physical health-related quality of life predicts stroke in the EPIC-Norfolk.

OBJECTIVE: To examine the relationship between Short Form (SF)-36 physical functional health-related quality of life and incident stroke. METHODS: A total of 13,615 men and women participating in the European Prospective Investigation into Cancer-Norfolk who were free of stroke, myocardial infarction, and cancer at baseline were included in the study. Participants completed a health and lifestyle questionnaire and attended a health examination during 1993 to 1997. Self-reported physical functional health was assessed using physical component summary scores of SF-36 18 months later. Stroke incidence was ascertained by death certification and hospital record linkage up to 2005. RESULTS: There were 244 incident strokes (total person years = 99,191). People who reported better physical functional health had significantly lower risk of incident stroke. Using Cox proportional hazard models adjusting for age, sex, body mass index, systolic blood pressure, cholesterol, smoking, diabetes, physical activity, social class, alcohol consumption, and respiratory function, men and women who were in the top quartile of SF-36 physical component summary scores had half the risk of stroke (RR = 0.50 [0.31, 0.78]) compared to the people in the bottom quartile. The relationships remained unchanged after excluding strokes occurring within the first 2 years of follow-up. CONCLUSIONS: Physical functional health-related quality of life measured as Short Form-36 predicts subsequent stroke risk independently of known risk factors in a general population. Poor physical functional health may indicate a high-risk population for stroke who may benefit most from targeted preventive interventions such as management of known risk factors.

HapMap-based study of the 17q21 ERBB2 amplicon in susceptibility to breast cancer.

ERBB2 is frequently amplified in breast tumours as part of a wide region of amplification on chromosome 17q21. This amplicon contains many candidate genes for breast cancer susceptibility. We used a genetic association study design to determine if common genetic variation (frequency>or=5%) in a 400-kb region surrounding ERBB2 and containing the PPARBP, CRK7, NEUROD2, PPP1R1B, STARD3, TCAP, PNMT, CAB2, ERBB2, C17ORF37, GRB7 and ZNFN1A3 genes, was associated with breast cancer risk. Sixteen tagging single-nucleotide polymorphisms (tSNPs) selected within blocks of linkage disequilibrium from the HapMap database, one HapMap singleton SNP, and six additional SNPs randomly selected from dbSNP were genotyped using Taqman in a large study set of British women (2275 cases, 2280 controls). We observed no association between any of the genotypes or associated haplotypes and disease risk. In order to simulate unidentified SNPs, we performed the leave-one-out cross-validation procedure on the HapMap data; over 90% of the common genetic variation was well represented by tagging polymorphisms. We are therefore likely to have tagged any common variants present in our population. In summary, we found no association between common genetic variation in the 17q21 ERBB2 amplicon and breast cancer risk in British women.

Dietary antioxidants and asthma in adults.

BACKGROUND: Several antioxidant nutrients have been reported to be inversely associated with asthma. A study was undertaken to assess the independent associations of these nutrients with asthma in adults. METHODS: A nested case-control study was performed in 515 adults with physician diagnosed asthma and 515 matched controls using dietary data obtained from 7 day food diaries. The main outcome measures were physician diagnosed asthma and current symptomatic asthma (diagnosed asthma and self-reported wheeze within the previous 12 months). RESULTS: Cases were similar to controls in age, sex, social class, and daily energy intake but had a lower median intake of fruit (132.1 v 149.1 g/day, p< or =0.05). 51.5% of the population reported zero consumption of citrus fruit; relative to these individuals, people who consumed >46.3 g/day had a reduced risk of diagnosed and symptomatic asthma (OR adjusted for potential confounders 0.59 (95% CI 0.43 to 0.82) and 0.51 (95% CI 0.33 to 0.79), respectively). In nutrient analysis, dietary vitamin C and manganese were inversely and independently associated with symptomatic asthma (adjusted OR per quintile increase 0.88 (95% CI 0.77 to 1.00) for vitamin C and 0.85 (95% CI 0.74 to 0.98) for manganese), but only manganese was independently associated with diagnosed asthma (OR 0.86 (95% CI 0.77 to 0.95)). Adjusted plasma levels of vitamin C were significantly lower in symptomatic cases than in controls (54.3 v 58.2 micromol/l, p = 0.003). CONCLUSIONS: Symptomatic asthma in adults is associated with a low dietary intake of fruit, the antioxidant nutrients vitamin C and manganese, and low plasma vitamin C levels. These findings suggest that diet may be a potentially modifiable risk factor for the development of asthma.

Respiratory function and self-reported functional health: EPIC-Norfolk population study.

Respiratory function is known to be associated with mortality. However, its association with health related quality of life (HRQoL) has not yet been examined. A population-based cross sectional study was conducted in 16,738 subjects aged 40-79 yrs and resident in Norfolk, to examine the association between forced expiratory volume in one second (FEV1) and HRQoL measured by the 36-item short form questionnaire. Individuals who were in the highest quintiles of FEV1 were more likely to report good physical functional health (odds ratio (OR) 1.60; 95% confidence interval (CI) 1.28-2.01 and OR 1.71; 95% CI 1.40-2.10 for males and females, respectively) controlling for age, height, weight or body mass index, smoking, physical activity, prevalent illness and social class. Being in the highest quintile for FEV1 was associated with significantly lower likelihood of poor self-reported mental functional health status in males (OR 0.78; 95% CI 0.61-0.99), but not in females (OR 1.00; 95% CI 0.82-1.22). In conclusion, forced expiratory volume in one second independently predicts self perceived physical well being in a general population across the whole normal distribution of respiratory function.

Further evidence for an HLA-related recessive mutation in nasopharyngeal carcinoma among the Chinese.

We typed 247 cases of nasopharyngeal carcinoma (NPC), a disease predominantly of the southern Chinese, and 274 controls from the Chao Shan region of China's Guangdong province for HLA A and B. Besides confirming the established associations with A2, A33, B46 and B58 (positive associations) and A11 (negative association), the results demonstrated a number of rarer alleles with strong negative association with NPC. Our data, combined with those from the previous studies in Southern Chinese, displayed the protective effects for A31 (odds ratio (OR)=0.0; 95% confidence interval (CI)=0-0.11), B13 (OR=0.50; 95% CI=0.35-0.69), B27 (OR=0.49; 95% CI=0.25-0.92), B39 (OR=0.18; 95% CI=0.06-0.48) and B55 (OR=0.32; 95% CI=0.14-0.68), the ORs comparing individuals with or without each allele. Other ethnic groups do not display such large HLA-associated variation in NPC risk. We show that a linked NPC gene with dominant mode of action could not generate such large protective effects. The results provide strong supporting evidence for the existence of a southern Chinese specific, recessive NPC gene closely linked to the HLA region as a major determinant of the Chinese risk for the disease.