Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers.

We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC.

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by (32)P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 micromol GSH g(-1) haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.

Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.

Aromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the (32)P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation-hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1-154C>A of CYP1A2 and the combination Tyrosine-Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10(-9) normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 x 10(-9)adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn.

Polychlorinated biphenyls in Spanish adults: determinants of serum concentrations.

BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population. OBJECTIVE: To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations. METHODS: Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD). RESULTS: The concentration of total PCBs was 459 ng/g lipids (or 3.1 microg/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 microg/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately. CONCLUSIONS: We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.

The ERICE-score: the new native cardiovascular score for the low-risk and aged Mediterranean population of Spain.

INTRODUCTION AND OBJECTIVES: In Spain, data based on large population-based cohorts adequate to provide an accurate prediction of cardiovascular risk have been scarce. Thus, calibration of the EuroSCORE and Framingham scores has been proposed and done for our population. The aim was to develop a native risk prediction score to accurately estimate the individual cardiovascular risk in the Spanish population. METHODS: Seven Spanish population-based cohorts including middle-aged and elderly participants were assembled. There were 11800 people (6387 women) representing 107915 person-years of follow-up. A total of 1214 cardiovascular events were identified, of which 633 were fatal. Cox regression analyses were conducted to examine the contributions of the different variables to the 10-year total cardiovascular risk. RESULTS: Age was the strongest cardiovascular risk factor. High systolic blood pressure, diabetes mellitus and smoking were strong predictive factors. The contribution of serum total cholesterol was small. Antihypertensive treatment also had a significant impact on cardiovascular risk, greater in men than in women. The model showed a good discriminative power (C-statistic=0.789 in men and C=0.816 in women). Ten-year risk estimations are displayed graphically in risk charts separately for men and women. CONCLUSIONS: The ERICE is a new native cardiovascular risk score for the Spanish population derived from the background and contemporaneous risk of several Spanish cohorts. The ERICE score offers the direct and reliable estimation of total cardiovascular risk, taking in consideration the effect of diabetes mellitus and cardiovascular risk factor management. The ERICE score is a practical and useful tool for clinicians to estimate the total individual cardiovascular risk in Spain.

Prevalence of Mental Disorders in the South-East of Spain, One of the European Regions Most Affected by the Economic Crisis: The Cross-Sectional PEGASUS-Murcia Project.

BACKGROUND: To describe the lifetime and 12-month prevalence, severity and age of onset distribution of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) disorders and to explore the association between socio-demographic variables and economic stressors with mental disorders during the economic crisis in the general population of Murcia (Spain). METHODS AND FINDINGS: The PEGASUS-Murcia Project is a cross-sectional face-to-face interview survey of a representative sample of non-institutionalized adults in Murcia administered between June 2010 and May 2012. DSM-IV disorders were assessed by the Composite International Diagnostic Interview (CIDI 3.0). Main outcome measures were lifetime and 12-month prevalence of Anxiety, Mood, Impulse and Substance Disorders, Severity and Age of Onset. Sociodemographic variables and stressful economic life events during the preceding 12 months were entered as independent variables in a logistic regression analysis. A total of 2,621 participants (67.4% response rate) were interviewed, 54.5% female, mean age 48.6 years. Twelve-month prevalence (95%CI) of disorders: anxiety 9.7% (7.6-12.2), mood 6.6% (5.5-8.1), impulse 0.3% (0.1-1.2) and substance use 1.0% (0.4-2.4) disorders. Lifetime prevalence: anxiety 15.0% (12.3-18.1), mood 15.6% (13.5-18.1), impulse 2.4% (1.4-4.0) and substance use 8.3% (6.2-11.0) disorders. Severity among 12-month cases: serious 29.2% (20.8-39.4), moderate 35.6% (24.0-49.1) and mild severity 35.2% (29.5-41.5). Women were 3.7 and 2.5 times more likely than men to suffer 12-month anxiety and mood disorders, respectively. Substance use was more frequent among men. Younger age and lower income were associated with higher prevalence. Respondents exposed to multiple and recent economic stressors had the highest risk of anxiety disorders. CONCLUSIONS: Mental disorders in the adult population of Murcia during the economic crisis were more prevalent and serious than those in previous estimates for Spain. Prevalence was strongly associated with exposure to stressors related to the economic crisis.

Changes in smoking habits in adults: results from a prospective study in Spain.

PURPOSE: We assessed changes in smoking behavior and its related factors among healthy adults from five regions in Spain. METHODS: The smoking status at recruitment and after 3 years was compared in 14,288 men and 23,983 women aged 35 to 64 years. The pattern of smoking and several lifestyle factors were investigated as potential predictors of subsequent changes in smoking habits. RESULTS: Among current smokers at baseline the age-adjusted rates of cessation per 1000 person-years were 57.4 for men and 43.2 for women. Among former smokers at baseline the relapse rates were 37.6 and 48.8 per 1000 person-years for men and women, respectively. The initiation rate per 1000 person-years among men who had never smoked was 12.5 and 2.7 for women. Higher amount currently smoked and longer time since quitting were strong predictors of lower rates of cessation and relapse, respectively, while age was associated with lower initiation rates in women. Increased alcohol consumption was related to low cessation and high relapse and initiation rates, mainly among men, while more educated women had higher cessation and initiation rates. CONCLUSIONS: The current pattern of changes in smoking behavior in Spanish populations aged 35 to 64 years results in rather small prevalence reduction. Additional efforts should be made to promote successful cessation and prevent initiation to reduce the tobacco burden in Spain.

Accuracy of self-reported diabetes, hypertension and hyperlipidemia in the adult Spanish population. DINO study findings.

INTRODUCTION AND OBJECTIVES: The aim of this study was to determine the accuracy of self-reported diabetes, hypertension and hyperlipidemia in a representative sample of adults (719 men and 837 women) from the south of Spain. METHODS: Self-reported data were gathered using a structured questionnaire. Biometric data recorded included blood glucose, total cholesterol and triglyceride concentrations and arterial systolic and diastolic blood pressures. The sensitivity, specificity, and positive and negative predictive values of self-reported diagnoses were calculated using the biometric data as the reference standard. The degree of overall agreement was determined using Cohen's kappa coefficient. RESULTS: The kappa values obtained indicated good agreement for self-reported diabetes (kappa=0.78), moderate agreement for hypertension (kappa=0.51), and minimal agreement for hyperlipidemia (kappa=0.27). Using the information reported, around 70% of diabetic cases were detected, along with half of hypertensive cases and 35% of hyperlipidemic cases. The specificity was high overall (>96%). The factors associated with an accurate self-reported diagnosis in subjects with disease included female sex and obesity (for hypertension), older age (for hyperlipidemia), a family history of disease (for diabetes) and having undergone blood pressure measurement (for all three conditions) or blood lipid measurement (for hypertension and hyperlipidemia) in the past year. CONCLUSIONS: The accuracy of self-reported diabetes was high, whereas that of self-reported hypertension or hyperlipidemia was lower. Further efforts are needed to increase awareness of these conditions among the population.

Serum levels of organochlorine pesticides in healthy adults from five regions of Spain.

The aim of this study was to measure of serum levels of p,p'-dichlorodiphenyl trichloroethane (p,p'-DDT), p,p'-dichlorodiphenyl dichlorethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB) in healthy adults in Spain. Furthermore, we also analyzed these levels according to dietary, other lifestyle factors and anthropometric characteristics. We measured the concentrations of such organochlorine pesticides (OCPs) in serum samples collected during 1992-1996 from 953 subjects aged 35-64 years, they were residents of five Spanish regions, they were randomly selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. OCPs were determined by means of gas chromatography with electron-capture detection (GC-ECD). The most frequent compound found in serum was p,p'-DDE, present in 98% of the samples, followed by HCB and beta-HCH, found in 89% and 77% of samples, respectively, while p,p'-DDT could be measured only in 26% of subjects. The geometric means of serum concentrations (ng/g lipid) were 822 for p,p'-DDE, 167 for beta-HCH, and 379 for HCB. The concentrations of all OCPs were positively associated with age and body mass index, and decreased along the period of blood collection. No association was found between OCPs levels and dietary factors. The concentrations of p,p'-DDE and beta-HCB were higher in Murcia, one of southern regions, most likely associated with intensive past use of pesticides related to agricultural practices, while higher levels of HCB were found in Navarra, located in the north, maybe due to industrial use rather than agricultural application.

Amount of DNA in plasma and cancer risk: a prospective study.

Levels of plasma DNA concentrations in cancer patients have been shown to be higher than the plasma DNA concentrations found in healthy subjects. The value of plasma DNA levels for development of neoplastic or pulmonary disease was evaluated in a large prospective study. Plasma samples (n = 1,184) were analyzed from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx, larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease (COPD), including never smokers and ex-smokers, from 9 countries across Europe. The amount of plasma DNA was variable across the European Prospective Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations in some centers might be due to the type of population recruited and/or the treatment of the samples. An elevated and statistically significant odds ratio (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06-6.02), while nonsignificant increased ORs were present for oral cancers, cancers of the pharynx and larynx and leukemia. When the analyses were stratified by time since recruitment (below or above 36 months), the increased ORs were limited to the more recent period of recruitment, i.e., a time elapsed between blood drawing and disease onset lower than 36 months. This was particularly true for COPD deaths (OR = 12.7; 95% CI = 1.57-103) and leukemia (OR = 2.37; 95% CI = 1.20-4.67).