[Show abstract][Hide abstract] ABSTRACT: Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations
for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known
or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive
interactions; specifically, the GSTM1 deletion polymorphism (Pinteraction ≤ .001), rs11892031 (UGT1A, Pinteraction = .01), and
rs798766 (TMEM129-TACC3-FGFR3, Pinteraction = .03). There was limited evidence for multiplicative interactions. When we
examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight
metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3,
Pinteraction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical
tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight
metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor
marker data to provide insight into the mechanisms of bladder carcinogenesis.
JNCI Journal of the National Cancer Institute 11/2015; 107(11). DOI:10.1093/jnci/djv223 · 12.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic and animal data indicate that night shift work might increase the risk for breast cancer. We evaluated the association of night work with different clinical types of breast cancer in a population based case-control study (MCC-Spain study) taking into account chronotype, an individual characteristic that may relate to night shift work adaptation. Lifetime occupational history was assessed by face-to-face interviews and shift work information was available for 1708 breast cancer cases and 1778 population controls from 10 Spanish regions, enrolled from 2008 to 2013. We evaluated three shift work domains, including shift work type (permanent vs rotating), lifetime cumulative duration and frequency. We estimated odds ratios (OR) for night work compared to day work using unconditional logistic regression models adjusting for confounders. Having ever worked permanent or rotating night shift was associated with an increased risk for breast cancer compared to day workers [odds ratio (OR) 1.18; 95 % CI 0.97, 1.43]. Chronotype was differentially associated with breast cancer depending on the duration of night shift work. Risk was higher in women with invasive tumors (OR 1.23; 95 % CI 1.00, 1.51) and for estrogen and progestagen positive tumors among premenopausal women (OR 1.44; 95 % CI 1.05, 1.99). Having ever performed night shift was associated with a small increased risk for breast cancer and especially in subgroups of women with particular hormone related characteristics.
European Journal of Epidemiology 07/2015; DOI:10.1007/s10654-015-0073-y · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To quantify serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds in former phenoxy herbicide production plant workers and firefighters, 20 years after 2,4,5-T production ceased.
Of 1025 workers employed any time during 1969-1984, 430 were randomly selected and invited to take part in a morbidity survey and provide a blood sample; 244 (57 %) participated. Firefighters stationed in close proximity of the plant and/or engaged in call-outs to the plant between 1962 and 1987 also participated (39 of 70 invited). Reported here are the serum concentrations of TCDD and other chlorinated dibenzo-dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs). Determinants of the serum concentrations were assessed using linear regression.
The 60 men who had worked in the phenoxy/TCP production area had a mean TCDD serum concentration of 19.1 pg/g lipid, three times the mean concentration of the 141 men and 43 women employed in other parts of the plant (6.3 and 6.0 pg/g respectively), and more than 10 times the mean for the firefighters (1.6 pg/g). Duration of employment in phenoxy herbicide synthesis, maintenance work, and work as a boilerman, chemist, and packer were associated with increased serum concentrations of TCDD and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD). Employment as a boilerman was also associated with elevated serum concentrations of PCBs.
Occupations in the plant associated with phenoxy herbicide synthesis had elevated levels of TCDD and PeCDD. Most other people working within the plant, and the local firefighters, had serum concentrations of dioxin-like compounds comparable to those of the general population.
International Archives of Occupational and Environmental Health 07/2015; DOI:10.1007/s00420-015-1074-6 · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aims to describe time trends in and patterns of use of hormonal contraception and postmenopausal hormone therapy and to identify factors associated with their use among Spanish women.
We performed a cross-sectional analysis using data from 1,954 population controls (aged 24-85 y) in 12 provinces of Spain who were enrolled in the Multi Case-Control Spain study (2007-2013). Data were collected from a questionnaire conducted face-to-face by trained personnel. We collected information on sociodemographic factors, lifestyle, sleep patterns, reproductive history, and occupational history.
Overall, 48.5% of Spanish women reported ever use of hormonal contraception, and 9.8% of women in the postmenopausal group reported use of postmenopausal hormone therapy. Younger cohorts used hormonal contraception for a longer period, whereas postmenopausal hormone therapy use dramatically dropped in the 2000s. Women with higher education levels (including education of partners) and smoking history were the most probable users of hormonal contraception, whereas inverse associations were observed among housewives, obese women, and nulliparous women. Postmenopausal hormone therapy use was associated with a surgical or therapeutic cause of menopause and with occupational history of rotating shifts.
In this Spanish population, several demographic, lifestyle, occupational, and reproductive factors are associated with use of hormonal compounds. Characterizing hormonal users and monitoring trends in the use of these hormonal compounds are essential from a public health perspective.
Menopause (New York, N.Y.) 06/2015; 72. DOI:10.1097/GME.0000000000000487 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The determination of dietary patterns in children examines the effects of the overall diet at early ages, instead of looking at individual foods or energy providing nutrients. The present analysis aims to identify the dietary patterns of preschool children and to examine their associations with multiple socio-economic and lifestyle characteristics.
Dietary data were collected for 1081 children participating in the Rhea mother-child cohort in Crete, Greece. Diet was assessed using a validated food frequency questionnaire, and dietary patterns were identified with principal component analysis. Multivariable linear regression models were used to examine factors associated with each dietary pattern.
Three dietary patterns were identified explaining 45.8% of the total diet variation. The 'Mediterranean' pattern was based on pulses, olive oil, vegetables, fish and fruits; the 'Snacky' pattern included potatoes and other starchy roots, salty snacks, sugar products and eggs; the 'Western' pattern contained cereals, cheese, added lipids, beverages and meat. Preschool attendance and increased time spent with the mother (⩾2 h/day) were positively associated with the 'Mediterranean' pattern, whereas watching TV was inversely associated with this pattern. Lower parental education, maternal age and earlier introduction to solid foods were positively associated with the 'Snacky' pattern. Higher scores on the 'Western' type diet were associated with exposure to passive smoking and watching TV. No variation in energy providing nutrient intake was observed across tertiles of the identified dietary patterns.
The results from this analysis indicate the important role of socio-demographic factors on children's dietary preferences in early age.European Journal of Clinical Nutrition advance online publication, 17 June 2015; doi:10.1038/ejcn.2015.93.
European journal of clinical nutrition 06/2015; DOI:10.1038/ejcn.2015.93 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The health effects of suspended particulate matter (PM) may depend on its chemical composition. Associations between maternal exposure to chemical constituents of PM and newborn's size have been little examined.
We aimed to investigate the associations of exposure to elemental constituents of PM with term low birth weight (LBW, weight<2,500 g among births after 37 weeks of gestation), mean birth weight and head circumference, relying on standardised fine-scale exposure assessment and with extensive control for potential confounders.
We pooled data from eight European cohorts comprising 34,923 singleton births in 1994-2008. Annual average concentrations of elemental constituents of PM smaller than 2.5 and 10 µm (PM2.5 and PM10) at maternal home addresses during pregnancy were estimated using land-use regression models. Adjusted associations between each birth measurement and concentrations of eight elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc) were calculated using random-effects regression on pooled data.
A 200 ng/m(3) increase in sulfur in PM2.5 was associated with an increased risk of LBW (adjusted odds ratio, 1.36, 95% confidence interval: 1.17, 1.58). Increased nickel and zinc in PM2.5 concentrations were also associated with an increased risk of LBW. Head circumference was reduced at higher exposure to all elements except potassium. All associations with sulfur were most robust to adjustment for PM2.5 mass concentration. All results were similar for PM10.
Sulfur, reflecting secondary combustion particles in this study, may adversely affect LBW and head circumference, independently of particle mass.
Environmental Health Perspectives 06/2015; DOI:10.1289/ehp.1409546 · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a case-control study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels ≤85 μg/L vs. >85 μg/L (N=68 and N=70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 μg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Δβ|≥0.05) located in eleven genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required.
[Show abstract][Hide abstract] ABSTRACT: Background
Evidence relating childhood cancer to high birthweight is derived primarily from registry and case–control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.Methods
We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥4.0 vs. <4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.ResultsA linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].Conclusion
Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.
[Show abstract][Hide abstract] ABSTRACT: Maternal pre-pregnancy obesity may increase the risk of childhood obesity but it is unknown whether other metabolic factors in early pregnancy such as lipid profile and hypertension are associated with offspring cardiometabolic traits.
Our objective was to investigate whether fasting lipid, glucose, and insulin levels during early pregnancy and maternal pre-pregnancy weight status, are associated with offspring adiposity measures, lipid levels and blood pressure at preschool age.
The study included 618 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. Pregnant women were recruited at the first prenatal visit (mean: 12weeks, SD: 0.7). A subset of 348 women provided fasting serum samples for glucose and lipid measurements. Outcomes measures were body mass index, abdominal circumference, sum of skinfold thickness, and blood pressure measurements at 4 years of age. A subsample of 525 children provided non-fasting blood samples for lipid measurements.
Pre-pregnancy overweight/obesity was associated with greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81), central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10mmHg in diastolic blood pressure in early pregnancy was associated with increased risk of offspring overweight/obesity (RR: 1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71mm (95% CI: 0.57, 2.86) at 4 years of age.
Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.
PLoS ONE 05/2015; 10(5):e0126327. DOI:10.1371/journal.pone.0126327 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed whether maternal employment during pregnancy - overall and in selected occupational sectors - is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design.
We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity.
Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (OR adj) 0.86, 95% confidence interval (95% CI) 0.81-0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (OR adj0.91, 95% CI 0.84-0.99) whereas food industry workers had an increased risk of preterm delivery (OR adj1.50, 95% CI 1.12-2.02). There was little evidence for heterogeneity between cohorts.
This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development.
Scandinavian Journal of Work, Environment & Health 05/2015; 41(4). DOI:10.5271/sjweh.3500 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Asthma, rhinitis, and eczema often co-occur in children but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis, and eczema using unsupervised statistical techniques.
We included 17,209 children at 4 years and 14,585 at 8 years from seven European-population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms "ever" and "in the last 12 months", doctor diagnosis, age of onset, and treatments of asthma, rhinitis, and eczema, IgE sensitisation, weight, and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organising maps.
Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70 and 79% of children, respectively) was characterised by a low prevalence of symptoms and sensitisation, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitisation. 99% children with comorbidities (co-occurrence of asthma, rhinitis, and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses.
At 4 and 8 years, at the population level, asthma, rhinitis, and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.