[Show abstract][Hide abstract] ABSTRACT: Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p'-DDE) can impair fetal growth; however, the exposure-response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure-response relationship between PCB-153 and p-p'-DDE and birth outcomes; to evaluate whether any no exposure-effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother-child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure-response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194g (95% CI -314, -74) per 1μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure-response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association.
Environment international 10/2014; · 6.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of biomarkers of early genetic effects, predictive for cancer, such as micronuclei (MN) in lymphocytes, may help to investigate the association between diet and cancer. We hypothesised that the presence of mutagens in the diet may increase MN formation. A 'pooled' standardised analysis was performed by applying the same experimental protocol for the cytokinesis block micronucleus assay in 625 young healthy women after delivery from five European study populations (Greece, Denmark, UK, Spain and Norway). We assessed MN frequencies in mono- and binucleated T-lymphocytes (MNMONO and MNBN) and the cytokinesis blocked proliferation index using a semi-automated image analysis system. Food frequency questionnaires (FFQs) were used to estimate intake of fatty acids and a broad range of immunotoxic and genotoxic/carcinogenic compounds through the diet. Pooled difference based on delivery type revealed higher MNMONO frequencies in caesarean than in vaginal delivery (P = 0.002). Statistical analysis showed a decrease in MNMONO frequencies with increasing calculated omega-6 PUFA concentrations and a decrease in MNBN frequencies with increasing calculated omega-3 PUFA concentrations. The expected toxic compounds estimated by FFQs were not associated with MN formation in mothers after delivery. In pregnant women, an omega-3 and -6 rich diet estimated by FFQ is associated with lower MN formation during pregnancy and delivery.
[Show abstract][Hide abstract] ABSTRACT: Background: Green spaces have been associated with both health benefits and risks in children; however, available evidence simultaneously investigating these conflicting influences, especially in association with different types of greenness, is scarce. Objectives: To simultaneously evaluate health benefits and risks associated with different types of greenness in children, in terms of sedentary behavior (represented by excessive screen time), obesity, current asthma, and allergic rhinoconjunctivitis. Methods: We conducted a cross-sectional study of a population-based sample of 3,178 schoolchildren (9-12 years old) in Sabadell, Spain (2006). Information on outcomes and covariates was obtained by questionnaire. We measured residential surrounding greenness as the average of satellite-derived Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, 500 m, and 1000 m around each home address. Residential proximity to green spaces was defined as living within 300 m of a forest or a park, as separate variables. We utilized logistic regression models to estimate associations separately for each exposure-outcome pair, adjusted for relevant covariates. Results: An inter-quartile range increase in residential surrounding greenness was associated with 11-19% lower relative prevalence of overweight/obesity and excessive screen time, but was not associated with current asthma and allergic rhinoconjunctivitis. Similarly, residential proximity to forests was associated with 39% and 25% lower relative prevalence of excessive screen time and overweight/obesity, respectively, but was not associated with current asthma. In contrast, living close to parks was associated with a 60% higher relative prevalence of current asthma, but had only weak negative associations with obesity/overweight or excessive screen time. Conclusion: We observed two separable patterns of estimated health benefits and risks associated with different types of greenness.
Environmental Health Perspectives 08/2014; · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the associations of individual maternal social capital and social capital dimensions (Participation in the Community, Feelings of Safety, Value of Life and Social Agency, Tolerance of Diversity) with adherence to the Mediterranean diet during pregnancy.
[Show abstract][Hide abstract] ABSTRACT: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
[Show abstract][Hide abstract] ABSTRACT: We assessed the association between occupational exposures and symptoms of chronic bronchitis and pulmonary ventilatory defects in a general population-based study of five areas in Spain. This study forms part of the European Community Respiratory Health Study (ECRHS). Subjects (n 5 1,735; age range, 20-44 yr; 52.4% of those initially selected) completed a respiratory questionnaire on symptoms and occupation and underwent baseline spirometry. Occupation was translated with an ad hoc developed job-exposure matrix (JEM) into none, low, and high exposure to biological dust, mineral dust, and gases and fumes. Exposure to high levels of biological dust was associated with cough for more than 3 mo (odds ratio (OR), 1.9; p 5 0.07), a reduction in FEF 25-75 to 478 ml/s (SD 178), and a reduction in FEV 1 to 151 mL (SD 71). These associations remained after excluding sub- jects with asthma symptoms or bronchial responsiveness. Smokers tended to have a higher risk for respiratory symptoms, but smoking did not modify the association of occupation with pulmonary function. Exposure to mineral dust and gases/fumes was less consistently related to pulmonary func- tion or to respiratory symptoms and this association further decreased after excluding subjects with asthma. In conclusion, exposure to high levels of biological dust in young adults is associated with symptoms of chronic bronchitis and pulmonary ventilatory defects, independently of asthma and smoking. Sunyer J, Kogevinas M, Kromhout H, Antó JM, Roca J, Tobias A, Vermeulen R, Payo F, Maldonado JA, Martinez-Moratalla J, Muniozguren N, and the Spanish Group of the Euro- pean Community Respiratory Health Survey. Pulmonary ventilatory defects and occupa- tional exposures in a population-based study in Spain. AM J RESPIR CRIT CARE MED 1998;157:512-517.
Am. J. Respir. Crit. Care Med. 157 (1998) 512-517. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.
European Respiratory Journal 07/2014; · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood.
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
Human Molecular Genetics 07/2014; · 7.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiological cancer studies on shift work have focused on breast cancer while evidence on other tumours is limited. We evaluated colorectal cancer risk in relation to night and rotating shift work and genetic variation, in a population based case-control study in Spain.
Occupational and environmental medicine. 06/2014; 71 Suppl 1:A5-6.
[Show abstract][Hide abstract] ABSTRACT: Established risk factors for leukaemia do not explain the majority of leukaemia. Previous studies have suggested the importance of occupation in leukaemogenesis. To evaluate associations between job title and leukaemia in the population the MCC-Spain We studied occupational variation of the risk of chronic lymphocytic leukaemia
Occupational and environmental medicine. 06/2014; 71 Suppl 1:A117-8.
[Show abstract][Hide abstract] ABSTRACT: Background: Light-at-night has been shown in experimental studies to disrupt melatonin production but this has only partly been confirmed in studies of night shift workers. In this cross-sectional study we examined the circadian variation of melatonin in relation to shift status, individual levels of light-at-night exposure and diurnal preference, an attribute reflecting personal preference for activity in the morning or evening. Methods: 117 workers (75 night and 42 day) of both sexes, aged 22-64 years, were recruited from four companies. Participants collected urine samples from all voids over 24 hours and wore a data logger continuously recording their light exposure. Socio-demographic, occupational, lifestyle and diurnal preference information were collected by interview. Urinary 6-sulfatoxymelatonin, the main melatonin metabolite, concentrations were measured. Results: Mean 6-sulfatoxymelatonin levels were lower in night (10.9 ng/mg creatinine/h; 95% CI, 9.5-12.6) compared to day workers (15.4; 95% CI, 12.3-19.3). The lowest 6-sulfatoxymelatonin levels were observed in night workers with morning preference (6.4; 95% CI, 3.0-13.6). Peak time of 6-sulfatoxymelatonin production occurred 3 hours later in night (08:42 h, 95% CI 07:48-09:42) compared to day workers (05:36 h, 95% CI 05:06-06:12). Phase delay was stronger among subjects with higher light-at-night exposure and number of nights worked. Conclusions: Night shift workers had lower levels and a delay in peak time of 6-sulfatoxymelatonin production over a 24 hour period. Differences were modified by diurnal preference and intensity of light-at-night exposure. Impact: Night shift work affects levels and timing of melatonin production and both parameters may relate to future cancer risk.
Cancer Epidemiology Biomarkers & Prevention 05/2014; · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Health benefits of swimming in pools may outweigh adverse health outcomes in children, but evidence from epidemiological studies is scarce or inconclusive for different health outcomes. We evaluated the association between indoor swimming pool attendance during childhood and respiratory and dermal conditions and symptoms in Catalan schoolchildren.
[Show abstract][Hide abstract] ABSTRACT: To build a predictive model for urothelial carcinoma of the bladder (UCB) risk combining both genomic and nongenomic data, 1,127 cases and 1,090 controls from the Spanish Bladder Cancer/EPICURO study were genotyped using the HumanHap 1M SNP array. After quality control filters, genotypes from 475,290 variants were available. Nongenomic information comprised age, gender, region, and smoking status. Three Bayesian threshold models were implemented including: (1) only genomic information, (2) only nongenomic data, and (3) both sources of information. The three models were applied to the whole population, to only nonsmokers, to male smokers, and to extreme phenotypes to potentiate the UCB genetic component. The area under the ROC curve allowed evaluating the predictive ability of each model in a 10-fold cross-validation scenario. Smoking status showed the highest predictive ability of UCB risk (AUCtest = 0.62). On the other hand, the AUC of all genetic variants was poorer (0.53). When the extreme phenotype approach was applied, the predictive ability of the genomic model improved 15%. This study represents a first attempt to build a predictive model for UCB risk combining both genomic and nongenomic data and applying state-of-the-art statistical approaches. However, the lack of genetic relatedness among individuals, the complexity of UCB etiology, as well as a relatively small statistical power, may explain the low predictive ability for UCB risk. The study confirms the difficulty of predicting complex diseases using genetic data, and suggests the limited translational potential of findings from this type of data into public health interventions.
[Show abstract][Hide abstract] ABSTRACT: Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study of smoking and bladder cancer risk based on primary scan data from 3,002 cases and 4,411 controls from the NCI Bladder Cancer Genome- Wide Association Study (GWAS). Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P-values <5x10(-5) were evaluated further in an independent dataset of 2,422 bladder cancer cases and 5,751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial data set and in the combined data set, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers (combined OR=1.34, 95% CI=1.20-1.50, P-value=5.18x10(-7)); and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR=0.75, 95% CI=0.67-0.84, P-value=6.35x10(-7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, while the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
[Show abstract][Hide abstract] ABSTRACT: Increased bronchial responsiveness is characteristic of asthma. Gas cooking, which is a major indoor source of the highly oxidant nitrogen dioxide, has been associated with respiratory symptoms and reduced lung function. However, little is known about the effect of gas cooking on bronchial responsiveness and on how this relationship may be modified by variants in the genes GSTM1, GSTT1 and GSTP1, which influence antioxidant defences.
The study was performed in subjects with forced expiratory volume in one second at least 70% of predicted who took part in the multicentre European Community Respiratory Health Survey, had bronchial responsiveness assessed by methacholine challenge and had been genotyped for GSTM1, GSTT1 and GSTP1-rs1695. Information on the use of gas for cooking was obtained from interviewer-led questionnaires. Effect modification by genotype on the association between the use of gas for cooking and bronchial responsiveness was assessed within each participating country, and estimates combined using meta-analysis.
Overall, gas cooking, as compared with cooking with electricity, was not associated with bronchial responsiveness (β=-0.08, 95% CI -0.40 to 0.25, p=0.648). However, GSTM1 significantly modified this effect (β for interaction=-0.75, 95% CI -1.16 to -0.33, p=4×10(-4)), with GSTM1 null subjects showing more responsiveness if they cooked with gas. No effect modification by GSTT1 or GSTP1-rs1695 genotypes was observed.
Increased bronchial responsiveness was associated with gas cooking among subjects with the GSTM1 null genotype. This may reflect the oxidant effects on the bronchi of exposure to nitrogen dioxide.
[Show abstract][Hide abstract] ABSTRACT: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onwards, complementing the genome.
The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterise early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "Early-Life Exposome". Here we describe the general design of the project.
In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totalling 32,000 mother-child pairs and biomarkers will be measured in a subset of 1,200. Nested repeat-sampling panel studies (N = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures.
HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step towards the life-course exposome.
Environmental Health Perspectives 03/2014; · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. Methods: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. Results: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). Conclusions: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.
British Journal of Cancer 03/2014; · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maternal exposure to dioxins and dioxin-like compounds may affect fetal growth and development. We evaluated the association between in utero dioxin-like activity and birth outcomes in a prospective European mother-child study.
We measured dioxin-like activity in maternal and cord blood plasma samples collected at delivery using the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX) bioassay in 967 mother-child pairs, in Denmark, Greece, Norway, Spain, and England. Multiple linear regression models were used to investigate the associations with birth weight, gestational age, and head circumference.
Plasma dioxin-like activity was higher in maternal sample than in cord samples. Birth weight was lower with medium (-58 g [95% confidence interval (CI) = -176 to 62]) and high (-82 g [-216 to 53]) tertiles of exposure (cord blood) compared with the lowest tertile. Gestational age was shorter by approximately half a week in the highest compared with the lowest (-0.4 weeks [95% CI = -0.8 to -0.1]). This association was stronger in boys than in girls, although the statistical evidence for interaction was weak (P = 0.22). Analysis based on CALUX-toxic equivalents expressed per milliliter of plasma showed similar trends. We found no association between dioxin-like activity in maternal plasma and birth outcomes.
Results from this international general population study suggest an association between low-level prenatal dioxin-like activity and shorter gestational age, particularly in boys, with weaker associations for birth weight.