Drinking Water Contaminants, Gene Polymorphisms, and Fetal Growth

There are still many uncertainties regarding the risk of adverse pregnancy outcomes associated with exposure to drinking water disinfection by-products. In Montréal, Québec, Canada, we carried out a hospital-based case–control study including 493 cases of intrauterine growth restriction defined as birth weight below the 10th percentile for gestational age and sex, according to Canadian standards. Controls were babies (n = 472) delivered at the same hospital whose birth weight was at or above the 10th percentile, matched for gestational age, race, and sex. Exposure to total and specific trihalomethanes was measured using regulatory data collected by municipalities and the provincial Ministry of Environment. Residential history, water drinking, and shower habits during pregnancy, as well as known risk factors for intrauterine growth restriction, were measured with a face-to-face interview with all mothers. Mothers and newborns were characterized for two genetic polymorphisms, one in the CYP2E1 gene (G1259C), and another in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T). Exposure to specific and total trihalomethanes from drinking water, determined for 458 cases and 426 controls, did not result in an increased risk of intrauterine growth restriction. However, significant effect modification was observed between newborns with and without the CYP2E1 variant; among newborns with the variant, the adjusted odds ratio for intrauterine growth restriction associated with exposure to average total trihalomethanes above the 90th percentile (corresponding to 29.4 μg/L) was 13.20 (95% confidence interval, 1.19–146.72). These findings suggest that exposure to trihalomethanes at the highest levels can affect fetal growth but only in genetically susceptible newborns

Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies

Exploration and comparison of methods for combining population- and family-based genetic association using the Genetic Analysis Workshop 17 mini-exome

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive rates for three existing methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare relative performance. We use knowledge of the underlying data simulation model to make these assessments

La relation chômage-santé : une étude prospective. Présentation sommaire et premiers résultats d’une recherche

Les auteurs ont entrepris en 1984 une importante étude sur les multiples interrelations entre le chômage et la santé. La méthodologie retenue est prospective, longitudinale, avec groupe contrôle. Ils présentent d'abord une synthèse des travaux effectués puis exposent les résultats obtenus jusqu'à maintenant. Ces résultats vont dans le sens des quatre hypothèses posées a priori. Cependant, ces résultats ne sont pas définitifs. L'analyse se poursuit.In 1984, the authors undertook a major study on the multiple interrelations between unemployment and health. Tlie methodology in use is prospective, longitudinal, with a control group. Their presentation consists of a synthesis of work carried out so far followed by corresponding results. These results are in compliance with the four hypotheses developed through a priori reasoning. However, these results are not definitive. The analysis continues

Maternal Exposure to Occupational Solvents and Childhood Leukemia

Many organic solvents are considered probable carcinogens. We carried out a population-based case–control study including 790 incident cases of childhood acute lymphoblastic leukemia and as many healthy controls, matched on age and sex. Maternal occupational exposure to solvents before and during pregnancy was estimated using the expert method, which involves chemists coding each individual’s job for specific contaminants. Home exposure to solvents was also evaluated. The frequency of exposure to specific agents or mixtures was generally low. Results were generally similar for the period ranging from 2 years before pregnancy up to birth and for the pregnancy period alone. For the former period, the odds ratio (OR), adjusted for maternal age and sex, for any exposure to all solvents together was 1.11 [95% confidence interval (CI), 0.88–1.40]. Increased risks were observed for specific exposures, such as to 1,1,1-trichloroethane (OR = 7.55; 95% CI, 0.92–61.97), toluene (OR = 1.88; 95% CI, 1.01–3.47), and mineral spirits (OR = 1.82; 95% CI, 1.05–3.14). There were stronger indications of moderately increased risks associated with exposure to alkanes (C5–C17; OR = 1.78; 95% CI, 1.11–2.86) and mononuclear aromatic hydrocarbons (OR = 1.64; 95% CI, 1.12–2.41). Risk did not increase with increasing exposure, except for alkanes, where a significant trend (p = 0.04) was observed. Home exposure was not associated with increased risk. Using an elaborate exposure coding method, this study shows that maternal exposure to solvents in the workplace does not seem to play a major role in childhood leukemia

Breastfeeding and risk of childhood brain tumors : a report from the Childhood Cancer and Leukemia International Consortium

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT

Nonchromosomal birth defects and risk of childhood acute leukemia : An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations

STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement

Julian Little and colleagues present the STREGA recommendations, which are aimed at improving the reporting of genetic association studies

Prévalence, incidence et facteurs de risque de la carie dentaire dans une cohorte d'âge scolaire élémentaire

A cohort of 2037 first year elementary school children was established in 1978 and examined annually on two other occasions to study the epidemiology of dental caries. Data on risk factors were collected from the parents through a questionnaire at the same time as the last two dental examinations. Some information on risk factors was also collected from the child at the time of dental examination. Prevalence of caries initially was high and the evolution of prevalence indices over the 24 month period is described. The incidence of caries for deciduous and permanent dentition is given by the relative increment of decay among teeth at risk at the beginning of the interval and those becoming at risk during the interval. Treatment level initially was low but increased between the second and third year of observation. Oral hygiene and nutritional habits did not conform to generally acceptable good preventive practices. Moreover, these behaviors are not stable. Whether by univariate (analyses of variance) or multivariate (multiple linear regression) analyses, certain factors consistently show an influence on dental caries. They are: father's schooling, presence of prostheses in parents, number of visits to the dentist, voluntary consumption of fluoride, number of years of this fluoride consumption, brushing, consumption of soft drinks, candies and vegetables, and eating before bed. These findings lend credence to the belief that despite continuing controversies about risk factors for dental caries, programs aimed at modifying behavior pertaining to the aforementioned factors are justified