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Abstract Background Emissions from refineries include a wide range of substances, such as chrome, lead, nickel, zinc, arsenic, cadmium, benzene, dioxins and furans, all of which are recognized by the International Agency for Research on Cancer (IARC) as carcinogens. Various studies have shown an association between non-Hodgkin lymphoma (NHL) and residence in the vicinity of industrial areas; however, evidence of specific association between refineries and residence in the vicinity has been suggested but not yet established. The aim of this study is to investigate potential links between environmental exposure to emissions from refineries and non-Hodgkin lymphoma mortality in Spain. The spatial distribution of NHL in Spain has an unusual pattern with regions some showing higher risk than others. Methods We designed an analysis of matched geographical areas to examine non-Hodgkin lymphoma mortality in the vicinity of the 10 refineries sited in Spain over the period 1997-2006. Population exposure to refineries was estimated on the basis of distance from town of residence to the facility in a 10 km buffer. We defined 10 km radius areas to perform the matching, accounting for population density, level of industrialization and socio-demographic factors of the area using principal components analysis. For the matched towns we evaluated the risk of NHL mortality associated with residence in the vicinity of the refineries and with different regions using mixed Poisson models. Then we study the residuals to assess a possible risk trend with distance. Results Relative risks (RRs) associated with exposure showed similar values for women and for men, 1.09 (0.97-1.24) and 1.12 (0.99-1.27). RRs for two regions were statistically significant: Canary Islands showed an excess of risk of 1.35 (1.05-1.72) for women and 1.50 (1.18-1.92) for men, whilst Galicia showed an excess of risk of 1.35 (1.04-1.75) for men, but not significant excess for women. Conclusions The results suggest a possible increased risk of NHL mortality among populations residing in the vicinity of refineries; however, a potential distance trend has not been shown. Regional effects in the Canary Islands and Galicia are significantly greater than the regional average.

Abstract Background Three IL-10 gene promoter single nucleotide polymorphisms -1082G > A, -819C > T and -592C > A and the haplotypes they define in Caucasians, GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of the IL-10 gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population. Methods 241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for -1082G > A and -592C > A SNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease. Results The -1082A allele (p = 0.027), A/A (p = 0.008) and ATA/ATA (p = 0.003) genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population. Conclusions Our results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia.

Background: Colorectal cancer (CRC) is the most frequently diagnosed cancer in Spain. Socioeconomic inequalities in cancer survival are not documented in Spain. We aim to study the association of socioeconomic inequalities with overall mortality and survival among CRC patients in southern Spain. Methods: We conducted a multilevel population-based cohort study, including CRC cases for the period 2011– 2013. The study time-to-event outcome was death, and the primary exposure was CRC patients' socioeconomic status assessed by the Spanish deprivation index at the census tract level. We used a mixed-effects flexible hazard model, including census tract as a random intercept, to derive overall survival estimates by deprivation. Results: Among 3589 CRC patients and 12,148 person-years at risk (pyr), 964 patients died before the end of the follow-up. Mortality by deprivation showed the highest mortality rate for the most deprived group (96.2 per 1000 pyr, 95% CI: 84.0– 110.2). After adjusting for sex, age, cancer stage, and the area of residence, the most deprived had a 60% higher excess mortality risk than the less deprived group (excess mortality risk ratio: 1.6, 95% CI: 1.1– 2.3). Conclusions: We found a consistent association between deprivation and CRC excess mortality and survival. The reasons behind these inequalities need further investigation in order to improve equality cancer outcomes in all social groups. [ABSTRACT FROM AUTHOR]

Our aims were to describe physical activity (PA) behaviour in Spain and to examine its association with the prevalence of some of the major non-communicable diseases and with the use of prescription medication. Individualized secondary data retrieved from the 2014 European Health Interview Survey (EHIS) for Spain were used to conduct a cross-sectional epidemiological study (n = 18926). PA was assessed by two different measures: a specific designed variable for EHIS and a leisure time PA frequency-based query of the national survey. Diseases analyzed were hypertension, diabetes, hypercholesterolemia, depression and anxiety. The use of prescription medication was also included in the study. Weighted percentages were computed and contingency tables were calculated to describe PA by levels of the traits and sociodemographic characteristics. Chi-square test was used to compare percentages between groups and weighted logistic regression models were used to assess the relationship between PA and the prevalence of the disease. About 73% of the Spanish population performs no PA at all or only occasionally during their leisure time, and only one third meets minimum PA international guidelines (≥ 150min/week). Men are considerably more active than women and less PA is observed as the education level decreases and as age increases. The risk of the diseases evaluated was up to three times higher among inactive individuals. This study provides national population-based estimations highlighting the impact of PA in Spain, not only in the prevalence of some of the major non-communicable diseases but also in reducing prescription medication, and the potential sex and socioeconomic influence. [ABSTRACT FROM AUTHOR]

Background Individual differences in breast size are a conspicuous feature of variation in human females and have been associated with fecundity and advantage in selection of mates. To identify common variants that are associated with breast size, we conducted a large-scale genotyping association meta-analysis in 7169 women of European descent across three independent sample collections with digital or screen film mammograms. Methods The samples consisted of the Swedish KARMA, LIBRO-1 and SASBAC studies genotyped on iCOGS, a custom illumina iSelect genotyping array comprising of 211 155 single nucleotide polymorphisms (SNPs) designed for replication and fine mapping of common and rare variants with relevance to breast, ovary and prostate cancer. Breast size of each subject was ascertained by measuring total breast area (mm2) on a mammogram. Results We confirm genome-wide significant associations at 8p11.23 (rs10086016, p=1.3×10−14) and report a new locus at 22q13 (rs5995871, p=3.2×10−8). The latter region contains the MKL1 gene, which has been shown to impact endogenous oestrogen receptor α transcriptional activity and is recruited on oestradiol sensitive genes. We also replicated previous genome-wide association study findings for breast size at four other loci. Conclusions A new locus at 22q13 may be associated with female breast size. [ABSTRACT FROM AUTHOR]

The article offers information on a research report related to the maintenance of attention and pathological gambling. It mentions that attentional bias between drug-related cues, craving, and relapse and was based on their reaction times (RTs) to probes replacing neutral and gambling-related cues. It revealed that pathological gamblers had attentional bias for gambling-related cues with exposure times that assess maintenance of attention.

Abstract: Background: Mammographic density (MD) is regarded as an intermediate phenotype in breast cancer development. This association study investigated the influence of 14 breast cancer susceptibility loci identified through previous genome-wide association studies on MD among the participants in the “Determinants of Density in Mammographies in Spain” (DDM-Spain) study. Methods: Our study covered a total of 3348 Caucasian women aged 45–68years, recruited from seven Spanish breast cancer screening centres having DNA available. Mammographic density was blindly assessed by a single reader using a semiquantitative scale. Ordinal logistic models, adjusted for age, body mass index and menopausal status, were used to estimate the association between each genotype and MD. Results: Evidence of association with MD was found for variant rs3803662 (TOX3) (Odds Ratio (OR)=1.13, 95% Confidence Interval (CI)=1.03–1.25), and marginal evidence of association for susceptibility loci rs3817198 (LSP1) (OR=1.09, 95% CI=1.00–1.20) and rs2981582 (FGFR2) (OR=0.92, 95% CI=0.84–1.01). Two other loci were associated with MD solely among pre-menopausal women, namely, rs4973768 (SLC4A7) (OR=0.83, 95% CI=0.70–1.00) and rs4415084 (MEPS30) (OR=1.22, 95% CI=1.00–1.49). Conclusions: Our findings lend some support to the hypothesis which links these susceptibility loci to MD. [Copyright &y& Elsevier]

Spatial aggregation of different industrial facilities leads to simultaneous release of pollutant emissions. Our objective is to study cancer mortality risk associated with residence in the vicinity of pollutant factories. We used data on industries for year 2007 (3458 facilities). For the 8,098 Spanish towns, we defined a factor with 4 levels based on the number of factories in a radius of 2.5 km from the centroid of each town (industrial factor).We also used data of land cover use to approximate the percentage of municipal land used for industrial activities in each Spanish town (land-used variable). For both variables we fitted Poisson models with random terms to account for spatial variation. We estimated risk trends related with increasing number of factories or percentage of land used for industrial activities. We studied 33 cancer causes. For the industrial factor, 11 causes showed trend associated with increasing factor level. For the land use variable, 8 causes showed statistically significant risks. Almost all tumours related to the digestive system and the respiratory system showed increased risks. Thus mortality by these tumours could be associated to residence in towns nearby industrial areas with positive trend linked to increasing levels of industrial activity. [ABSTRACT FROM AUTHOR]

Background: Three IL-10 gene promoter single nucleotide polymorphisms -1082G > A, -819C > T and -592C > A and the haplotypes they define in Caucasians, GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sexdependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of the IL-10 gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population. Methods: 241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for -1082G > A and -592C > A SNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease. Results: The -1082A allele (p = 0.027), A/A (p = 0.008) and ATA/ATA (p = 0.003) genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population. Conclusions: Our results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci.

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model.

Objectives: To investigate the trends and correlations of gross domestic product (GDP) adjusted for purchasing power parity (PPP) per capita on suicide rates in 10 WHO regions during the past 30 years., Design: Analyses of databases of PPP-adjusted GDP per capita and suicide rates. Countries were grouped according to the Global Burden of Disease regional classification system., Data Sources: World Bank's official website and WHO's mortality database., Statistical Analyses: After graphically displaying PPP-adjusted GDP per capita and suicide rates, mixed effect models were used for representing and analysing clustered data., Results: Three different groups of countries, based on the correlation between the PPP-adjusted GDP per capita and suicide rates, are reported: (1) positive correlation: developing (lower middle and upper middle income) Latin-American and Caribbean countries, developing countries in the South East Asian Region including India, some countries in the Western Pacific Region (such as China and South Korea) and high-income Asian countries, including Japan; (2) negative correlation: high-income and developing European countries, Canada, Australia and New Zealand and (3) no correlation was found in an African country., Conclusions: PPP-adjusted GDP per capita may offer a simple measure for designing the type of preventive interventions aimed at lowering suicide rates that can be used across countries. Public health interventions might be more suitable for developing countries. In high-income countries, however, preventive measures based on the medical model might prove more useful.

Despite marked morbidity and mortality associated with suicidal behavior, accurate identification of individuals at risk remains elusive. The goal of this study is to identify a model based on single nucleotide polymorphisms (SNPs) that discriminates between suicide attempters and non-attempters using data mining strategies. We examined functional SNPs (n = 840) of 312 brain function and development genes using data mining techniques. Two hundred seventy-seven male psychiatric patients aged 18 years or older were recruited at a University hospital psychiatric emergency room or psychiatric short stay unit. The main outcome measure was history of suicide attempts. Three SNPs of three genes (rs10944288, HTR1E; hCV8953491, GABRP; and rs707216, ACTN2) correctly classified 67% of male suicide attempters and non-attempters (0.50 sensitivity, 0.82 specificity, positive likelihood ratio = 2.80, negative likelihood ratio = 1.64). The OR for the combined three SNPs was 4.60 (95% CI: 1.31-16.10). The model's accuracy suggests that in the future similar methodologies may generate simple genetic tests with diagnostic utility in identification of suicide attempters. This strategy may uncover new pathophysiological pathways regarding the neurobiology of suicidal acts., ((c) 2009 Wiley-Liss, Inc.)