European Prospective Investigation Of Cancer Research Articles

OP0117 HDL-C and HBA1C predict the development of inflammatory polyarthritis: Results from the european prospective investigation of cancer (norfolk) and the norfolk arthritis register (EPIC-2-NOAR study)

BackgroundRheumatoid Arthritis (RA) is associated with accelerated atherosclerosis and inflammation associated with RA may increase the propensity to develop dyslipidaemia and insulin resistance. In established RA, HDL-C (HDL) and ApoA-1...

Using lifestyle factors to identify individuals at higher risk of inflammatory polyarthritis (results from the European Prospective Investigation of Cancer-Norfolk and the Norfolk Arthritis Register—the EPIC-2-NOAR Study)

ObjectivesTo investigate the association of lifestyle factors with risk of inflammatory polyarthritis (IP) and rheumatoid arthritis (RA).MethodsThe European Prospective Investigation of Cancer, Norfolk, UK (EPIC-Norfolk) gathered lifestyle data from participants...

Change in HbA1c over 3 years does not improve the prediction of cardiovascular disease over and above HbA1c measured at a single time point

Aims/hypothesisHbA1c is an important risk factor for cardiovascular disease (CVD), with 1% higher HbA1c levels associated with a 10–20% increased risk of CVD. Little is known about the association between change in HbA1c over time and cardiovascular risk in non-diabetic populations. This study examined the association between change in HbA1c over time and cardiovascular risk in a non-diabetic British population.MethodsWe used data on HbA1c collected at baseline and at a second health examination 3 years later among a population of 5,790 non-diabetic men and women who participated in the European Prospective Investigation of Cancer (EPIC)–Norfolk. The association between change in HbA1c over 3 years and incident cardiovascular events over the following 8 years was examined using multivariate Cox regression. We also examined whether information on change in HbA1c over time improved prediction of cardiovascular events over a single measure of HbA1c by comparing the area under the receiver operating characteristic curves (aROC) and computing the net reclassification improvement.ResultsThe mean change (SD) in HbA1c over 3 years was 0.13% (0.52). During 44,596 person-years of follow-up, 529 cardiovascular events occurred (incidence 11.9 per 1,000 person-years). Each 0.5% rise in HbA1c over 3 years was associated with a 9% increase in risk of a cardiovascular event (HR 1.09; 95% CI 1.01, 1.18) after adjustment for baseline HbA1c and other major cardiovascular risk factors. However, change in HbA1c was not associated with cardiovascular risk after adjustment for HbA1c at follow-up. Multivariate models with and without information on change in HbA1c over time showed a similar aROC of 0.78. Adding change in HbA1c to the model with HbA1c at follow-up did not improve risk classification.Conclusions/interpretationAddition of information on change in HbA1c over 3 years did not improve the prediction of CVD over and above information on HbA1c and other major cardiovascular risk factors from a single time point.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-2854-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

The EPIC-Norfolk Eye Study: rationale, methods and a cross-sectional analysis of visual impairment in a population-based cohort

ObjectivesTo summarise the methods of the European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study, and to present data on the prevalence of visual impairment and associations with visual impairment in...

Validation of a model to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD: the rotterdam ischemic heart disease and stroke computer simulation (RISC) model

BackgroundWe developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established.MethodsThe Rotterdam Ischemic Heart Disease and Stroke Computer Simulation (RISC) model was developed using data covering 5 years of follow-up from the Rotterdam Study. To prove 1) internal and 2) predictive validity, the incidences of coronary heart disease (CHD), stroke, CVD death, and non-CVD death simulated by the model over a 13-year period were compared with those recorded for 3,478 participants in the Rotterdam Study with at least 13 years of follow-up. 3) External validity was verified using 10 years of follow-up data from the European Prospective Investigation of Cancer (EPIC)-Norfolk study of 25,492 participants, for whom CVD and non-CVD mortality was compared.ResultsAt year 5, the observed incidences (with simulated incidences in brackets) of CHD, stroke, and CVD and non-CVD mortality for the 3,478 Rotterdam Study participants were 5.30% (4.68%), 3.60% (3.23%), 4.70% (4.80%), and 7.50% (7.96%), respectively. At year 13, these percentages were 10.60% (10.91%), 9.90% (9.13%), 14.20% (15.12%), and 24.30% (23.42%). After recalibrating the model for the EPIC-Norfolk population, the 10-year observed (simulated) incidences of CVD and non-CVD mortality were 3.70% (4.95%) and 6.50% (6.29%). All observed incidences fell well within the 95% credibility intervals of the simulated incidences.ConclusionsWe have confirmed the internal, predictive, and external validity of the RISC model. These findings provide a basis for analyzing the effects of modifying cardiovascular disease risk factors on the burden of CVD with the RISC model.

Lipoprotein(a) and risk of coronary, cerebrovascular, and peripheral artery disease: the EPIC-Norfolk prospective population study.

Although the association between circulating levels of lipoprotein(a) [Lp(a)] and risk of coronary artery disease (CAD) and stroke is well established, its role in risk of peripheral arterial disease (PAD) remains unclear. Here, we examine the association between Lp(a) levels and PAD in a large prospective cohort. To contextualize these findings, we also examined the association between Lp(a) levels and risk of stroke and CAD and studied the role of low-density lipoprotein as an effect modifier of Lp(a)-associated cardiovascular risk. Lp(a) levels were measured in apparently healthy participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. Cox regression was used to quantify the association between Lp(a) levels and risk of PAD, stroke, and CAD outcomes. During 212 981 person-years at risk, a total of 2365 CAD, 284 ischemic stroke, and 596 PAD events occurred in 18 720 participants. Lp(a) was associated with PAD and CAD outcomes but not with ischemic stroke (hazard ratio per 2.7-fold increase in Lp(a) of 1.37, 95% CI 1.25-1.50, 1.13, 95% CI 1.04-1.22 and 0.91, 95% CI 0.79-1.03, respectively). Low-density lipoprotein cholesterol levels did not modify these associations. Lp(a) levels were associated with future PAD and CAD events. The association between Lp(a) and cardiovascular disease was not modified by low-density lipoprotein cholesterol levels.

The association between myopia and glaucoma ‐ causality or classification?

AbstractMyopia is frequently cited as a risk factor for glaucoma, based on findings from many epidemiological studies. However, these studies are potentially subject to misclassification bias. Glaucoma is largely diagnosed based on optic disc cupping together with a visual field defect. Myopic patients may also have anomalous (or difficult to assess) optic discs together with visual field defects. This talk will examine the epidemiological link between myopia and glaucoma, and address the question whether the observed association between myopia and glaucoma is causal. Published evidence will be critically reviewed and supplemented with the findings from the EPIC‐Norfolk Eye Study (European Prospective Investigation of Cancer).

Estimating the potential population impact of stepwise screening strategies for identifying and treating individuals at high risk of Type 2 diabetes: a modelling study.

BackgroundDiabetes risk assessment has been proposed as part of the National Health Service Health Checks programme, and HbA1c has recently been recommended as a diagnostic test for diabetes at a threshold of 48 mmol/mol (6.5%). We estimated the potential population impact of different stepwise screening strategies to identify individuals at high risk who might be offered preventive interventions.MethodsUsing data from 5910 participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with HbA1c measurements, we modelled different stepwise screening strategies for identifying and treating individuals at high risk of Type 2 diabetes using different HbA1c cut-off points with and without a stage of prestratification. For each strategy, we estimated the number needed to have a diagnostic test, the number needed to treat to prevent one new case of Type 2 diabetes, and the number of new cases that could be prevented in the population over 3 years. Relative risk reductions for estimated effects of intensive lifestyle intervention were derived from the US Diabetes Prevention Program.ResultsCompared with inviting all individuals in an average primary care trust for a diagnostic test, a stepwise screening approach using simple routine data such as age and anthropometric indices could prevent a slightly lower number (lower-upper estimates) of new cases of Type 2 diabetes over 3 years (224 [130–359] and 193 [109–315] cases respectively) but would only require half the population to be invited for a diagnostic blood test. A total of 162 (88–274) cases could be prevented by inviting individuals with a Cambridge risk score of ≥ 0.15, with only 40% of the total population requiring diagnostic blood tests. Using a participant completed questionnaire for risk assessment (FINDRISC) was less effective, mainly relating to the questionnaire response rate. Providing preventive interventions to those with a lower HbA1c of 37–< 48 mmol/mol (5.5–< 6.5%) could prevent more cases but with a disproportionately higher workload, compared with using the recommended HbA1c threshold of 42–< 48 mmol/mol (6.0–< 6.5%).ConclusionsCompared with mass screening, an approach using routine data for risk stratification followed by an HbA1c test with a threshold of 42–< 48 mmol/mol (6.0–< 6.5%) for identifying individuals suitable for preventive interventions might prevent slightly fewer cases of Type 2 diabetes but with potential cost-savings.

A Latent Variable Partial Least Squares Path Modeling Approach to Regional Association and Polygenic Effect with Applications to a Human Obesity Study

Genetic association studies are now routinely used to identify single nucleotide polymorphisms (SNPs) linked with human diseases or traits through single SNP-single trait tests. Here we introduced partial least squares path modeling (PLSPM) for association between single or multiple SNPs and a latent trait that can involve single or multiple correlated measurement(s). Furthermore, the framework naturally provides estimators of polygenic effect by appropriately weighting trait-attributing alleles. We conducted computer simulations to assess the performance via multiple SNPs and human obesity-related traits as measured by body mass index (BMI), waist and hip circumferences. Our results showed that the associate statistics had type I error rates close to nominal level and were powerful for a range of effect and sample sizes. When applied to 12 candidate regions in data (N = 2,417) from the European Prospective Investigation of Cancer (EPIC)-Norfolk study, a region in FTO was found to have stronger association (rs7204609∼rs9939881 at the first intron P = 4.29×10−7) than single SNP analysis (all with P>10−4) and a latent quantitative phenotype was obtained using a subset sample of EPIC-Norfolk (N = 12,559). We believe our method is appropriate for assessment of regional association and polygenic effect on a single or multiple traits.

A comparative analysis of three widely used lipid management guidelines in the EPIC-Norfolk cohort

To compare the impact of three major guidelines for the prevention of cardiovascular disease (CVD). 21,263 men and women aged 39-79 years from the EPIC (European Prospective Investigation of Cancer) Norfolk cohort were retrospectively classified at baseline by statin therapy recommendations according to the NICE, ESC and ATPIII CVD prevention guidelines. Recommendations based on baseline data were related to 10-year follow-up to calculate number of new CVD events that could be prevented by statins, number-needed-to-treat (NNT) and CVD incidence decrease. Statin therapy was recommended to 34% by the NICE guideline, 29% by ESC and 32% by ATPIII. A total of 263 events could potentially have been prevented by application of the NICE guideline, 219 by ESC and 199 by ATPIII. The NNT with statins over 10 years was 27 with the NICE guideline, 28 with ESC and 34 with ATPIII. Application of the NICE guideline could have decreased CVD incidence by 13%; using ESC guidelines the figure is 11% and with ATPIII it is 10%. The NICE guideline selected greater percentages of elderly and subjects with prevalent CVD risk factors. It performed best in recommending statins and could have prevented the greatest number of CVD events. With all guidelines, nearly half the subjects who developed a CVD event were not considered eligible for statins at baseline. Less selective prevention strategies need to be explored.

The association between prior infection with five serotypes of Coxsackievirus B and incident type 2 diabetes mellitus in the EPIC-Norfolk study.

Infections with Coxsackieviruses have been linked to beta cell dysfunction. Given the importance of beta cell dysfunction in the aetiology of type 2 diabetes, we hypothesised that prior infection with Coxsackieviruses B would increase the risk of type 2 diabetes. The aims of the study were to estimate cross-sectional associations between potential predictors of previous infection and seropositivity for Coxsackievirus B serotypes 1-5 (CBV1-5), and then to assess the association between seropositivity and incident type 2 diabetes. Using a case-cohort design nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk study, we ascertained n = 603 cases of incident type 2 diabetes. From within the entire cohort we identified a random subcohort of n = 835, without diabetes at baseline. The presence of Coxsackievirus B neutralising antibodies against serotypes 1-5 was assessed using a plaque neutralisation assay. Weighted Cox regression was used to examine the association between presence of antibodies to CBV1-5 and the development of type 2 diabetes. Seropositivity in the subcohort for CBV1-5 was 50%, 67%, 66%, 75% and 45%, respectively. After adjustment for age, sex, BMI, physical activity and family history of diabetes, the presence of antibodies against CBV1-5 was not associated with incident type 2 diabetes, over a mean follow-up of 5.7 years (HR [95% CIs] 0.94 [0.72,1.25], 0.92 [0.68, 1.23], 1.33 [0.98,1.81], 1.16 [0.83,1.61] and 1.03 [0.77,1.39] for CBV1-5, respectively). The presence of antibodies against any of five serotypes of Coxsackievirus B was not associated with incident type 2 diabetes.

Is Hyperglycemia a Cardiovascular Risk Factor?

Patients with diabetes show an increased vascular morbidity and mortality that reduces their life expectancy by ~5–15 years (depending on the age at diagnosis) (1). There is convincing evidence from epidemiological and pathophysiological studies that hyperglycemia per se is largely responsible for the harmful effects of the disease. As recently shown by clinical trials, treatment of this condition may reduce cardiovascular events and mortality, and several therapies should be considered: initiating early and individualized treatment and avoiding hypoglycemia. As shown in the Multiple Risk Factor Intervention Trial, at any given level of major cardiovascular risk factors, diabetes is associated with an odds ratio of 2–4 for cardiovascular mortality compared with nondiabetic subjects (2). These results were confirmed by the European Prospective Investigation of Cancer and Nutrition (EPIC Norfolk) study (3) and a recent analysis of the Atherosclerosis Risk in Communities (ARIC) study (4). Furthermore, a recently published 18-year follow-up study from Finland demonstrated a similar impact of type 1 and type 2 diabetes on cardiovascular mortality. The adjusted hazard ratios compared with age-matched subjects without diabetes were 5.2 and 4.9 for type 1 and type 2 diabetes, respectively (5). Thus, today evidence exists on long-term follow-up population-based studies in patients with type 1 and type 2 diabetes. This evidence clearly suggests that hyperglycemia is a key risk factor not only for diabetes-related disease, but also for cardiovascular and all-cause mortality. On the basis of these long-term observations, one can assume an increment of cardiovascular disease per increase of 1 unit (%) A1C of ~18% (6). As shown in numerous prospective studies, the deleterious effects of dysglycemia (fasting and postprandial hyperglycemia) develop before diabetes is diagnosed. In the Glucose Tolerance in Acute Myocardial Infarction study of patients with acute coronary syndrome, abnormal glucose tolerance was the strongest independent …

Incidence of Type 2 Diabetes Using Proposed HbA1c Diagnostic Criteria in the European Prospective Investigation of Cancer–Norfolk Cohort

OBJECTIVETo evaluate the incidence and relative risk of type 2 diabetes defined by the newly proposed HbA1c diagnostic criteria in groups categorized by different baseline HbA1c levels.RESEARCH DESIGN AND METHODSUsing data from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with repeat HbA1c measurements, we estimated the prevalence of known and previously undiagnosed diabetes at baseline (baseline HbA1c ≥6.5%) and the incidence of diabetes over 3 years. We also examined the incidence and corresponding odds ratios (ORs) by different levels of baseline HbA1c. Incident diabetes was defined clinically (self-report at follow-up, prescribed diabetes medication, or inclusion on a diabetes register) or biochemically (HbA1c ≥6.5% at the second health assessment), or both.RESULTSThe overall prevalence of diabetes was 4.7%; 41% of prevalent cases were previously undiagnosed. Among 5,735 participants without diabetes at baseline (identified clinically or using HbA1c criteria, or both), 72 developed diabetes over 3 years (1.3% [95% CI 1.0–1.5]), of which 49% were identified using the HbA1c criteria. In 6% of the total population, the baseline HbA1c was 6.0–6.4%; 36% of incident cases arose in this group. The incidence of diabetes in this group was 15 times higher than in those with a baseline HbA1c of <5.0% (OR 15.5 [95% CI 7.2–33.3]).CONCLUSIONSThe cumulative incidence of diabetes defined using a newly proposed HbA1c threshold in this middle-aged British cohort was 1.3% over 3 years. Targeting interventions to individuals with an HbA1c of 6.0–6.4% might represent a feasible preventive strategy, although complementary population-based preventive strategies are also needed to reduce the growing burden of diabetes.

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

Aims/hypothesisObesity 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.MethodsWe 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.ResultsOf 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/interpretationThe genetic predisposition to obesity leads to increased risk of developing type 2 diabetes, which is completely mediated by its obesity-predisposing effect.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2044-5) contains supplementary material, which is available to authorized users.

Assessing the impact of road traffic on cycling for leisure and cycling to work

BackgroundTo explore the relationship between leisure and commuter cycling with objectively measured levels of road traffic and whether any relationship was affected by traffic levels directly outside of home or in local neighbourhood.FindingsWe conducted a secondary analysis of data from the UK European Prospective Investigation of Cancer (EPIC) Norfolk cohort in 2009. We used a geographical information system (GIS) and gender specific multivariate models to relate 13 927 participants' reported levels of cycling with an index of road traffic volume (Road Traffic Volume Index Score - RTVIS). RTVIS were calculated around each participants home, using four distance based buffers, (0.5 km, 1 km, 2 km and 3.2 km). Models were adjusted for age, social status, education, car access and deprivation. Both genders had similar decreases in leisure cycling as traffic volumes increased at greater distances from home (OR 0.42, (95% CI 0.32-0.52, p < 0.001) for women and OR 0.41, (95% CI 0.33-0.50, p < 0.001) for men in the highest quartile at 3.2 km). There was no effect of traffic volumes at any distance on commuter cycling.ConclusionsTraffic volumes appear to have greater impact on leisure cycling than commuter cycling. Future research should investigate the importance of traffic on different types of cycling and include psychosocial correlates.

Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study

ObjectiveThe value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual's risk of CHD is unclear. In the European...

Oxidation-Specific Biomarkers, Lipoprotein(a), and Risk of Fatal and Nonfatal Coronary Events

This study sought to assess whether oxidation-specific biomarkers are associated with an increased risk of coronary artery disease (CAD) events. The relationship of a panel of oxidative biomarkers and lipoprotein(a) [Lp(a)] to CAD risk is not fully determined. A prospective case-control study nested in the EPIC (European Prospective Investigation of Cancer)-Norfolk cohort of 45- to 79-year-old apparently healthy men and women followed for approximately 6 years was designed. Cases consisted of participants in whom fatal or nonfatal CAD developed, matched by sex, age, and enrollment time with controls without CAD. Baseline levels of oxidized phospholipids on apolipoprotein B-100 particles and Lp(a) were measured in 763 cases and 1,397 controls. Their relationship to secretory phospholipase A(2) type IIA mass and activity, myeloperoxidase mass, and lipoprotein-associated phospholipase A(2) activity and association with CAD events were determined. After adjusting for age, smoking, diabetes, low- and high-density lipoprotein cholesterol, and systolic blood pressure, the highest tertiles of oxidized phospholipids on apolipoprotein B-100 particles and Lp(a) were associated with a significantly higher risk of CAD events (odds ratios: 1.67 and 1.64, respectively; p < 0.001) compared with the lowest tertiles. The odds ratio of CAD events associated with the highest tertiles of oxidized phospholipids on apolipoprotein B-100 particles or Lp(a) was significantly potentiated (approximately doubled) by the highest tertiles of secretory phospholipase A(2) activity and mass but less so for myeloperoxidase and lipoprotein-associated phospholipase A(2) activity. The odds ratios for fatal CAD were higher than for the combined end point. After taking into account the Framingham Risk Score, c-index values progressively increased when oxidative biomarkers were added to the model. This EPIC-Norfolk study links pathophysiologically related oxidation-specific biomarkers and Lp(a) with CAD events. Oxidation-specific biomarkers provide cumulative predictive value when added to traditional cardiovascular risk factors.

Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study

We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS) increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study. We genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y) from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI)-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error [SE] 0.012) kg/m(2) (p = 6.73 x 10(-37)) increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall). This association was significantly (p(interaction) = 0.005) more pronounced in inactive people (0.205 [SE 0.024] kg/m(2) [p = 3.62 x 10(-18); 592 g in weight]) than in active people (0.131 [SE 0.014] kg/m(2) [p = 7.97 x 10(-21); 379 g in weight]). Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26)) in the whole population, but significantly (p(interaction) = 0.015) more in inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(-16)]) than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1.15 x 10(-12)]). Consistent with the cross-sectional observations, physical activity modified the association between the genetic predisposition score and change in BMI during follow-up (p(interaction) = 0.028). Our study shows that living a physically active lifestyle is associated with a 40% reduction in the genetic predisposition to common obesity, as estimated by the number of risk alleles carried for any of the 12 recently GWAS-identified loci. Please see later in the article for the Editors' Summary.

A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1 -2 and -3 in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background: Height and BMI are risk factors for several types of cancer and may be related to circulating concentrations of insulin-like growth factor-I (IGF-I), a peptide associated with increased cancer risk.Aim: To assess the associations between height, BMI and serum concentrations of IGF-I and IGF binding protein (IGFBP)-1, -2 and -3.Subjects and methods: This cross-sectional analysis included 1142 men and 3589 women aged 32–77 years from the multi-centre study, the European Prospective Investigation of Cancer and Nutrition (EPIC).Results: In men, there was a positive association between height and IGF-I; each 10 cm increment in height was associated with an increase in IGF-I concentrations of 4.3% (95% confidence interval (CI): 1.3–7.5%, p for trend = 0.005), but this association was not statistically significant for women (0.9%, 95% CI: − 0.7 to 2.6%, p for trend = 0.264). In both men and women, the association between IGF-I and BMI was non-linear and those with a BMI of 26–27 kg/m2 had the highest IGF-I concentration. BMI was strongly inversely related to concentrations of IGFBP-1 and IGFBP-2 in men and in women (p for trend for all < 0.001).Conclusion: Height and BMI are associated with IGF-I and its binding proteins, which may be mechanisms through which body size contributes to increased risk of several cancers.

Persistent infection by HCV and EBV in peripheral blood mononuclear cells and risk of non-Hodgkin's lymphoma

Hepatitis C virus (HCV) and Epstein–Barr virus (EBV) have been repeatedly associated with risk of non-Hodgkin's lymphoma (NHL) in studies focusing on serological evidence of infection. We investigated NHL risk in association with detection of HCV-RNA or EBV-DNA in the peripheral blood mononuclear cells (PBMC). The study involved 91 NHL cases and 182 controls nested in the Italian branch of the EPIC (European Prospective Investigation of Cancer and nutrition) cohort, which obtained blood samples from 47,749 healthy volunteers between 1993 and 1998 in 5 Italian cities. NHL cases were identified until June 2005 through linkage with records of the Cancer, Mortality, and Hospital Discharge Registries. For all study subjects, we performed viral genome analyses on DNA and RNA extracted from buffy-coats and analysed EBV and HCV antibodies. The odds ratios (ORs) of NHL were 1.2 (95% confidence intervals: 0.4–3.8; 5 exposed cases) for PBMC HCV infection and 1.2 (0.7–2.3; 24 exposed cases) for PBMC EBV infection. Similar OR estimates were found for detection of EBV and HCV antibodies. These null results, although based on a relatively small sample size, suggest that persistent EBV and HCV infection in the PBMC is not a stronger predictor of NHL risk than serological evidence of infection.