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An exploratory case‐only analysis of gene‐hazardous air pollutant interactions and the risk of childhood medulloblastoma
Author(s) -
Lupo Philip J.,
Lee Laura J.,
Okcu M. Fatih,
Bondy Melissa L.,
Scheurer Michael E.
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24105
Subject(s) - medicine , medulloblastoma , odds ratio , context (archaeology) , trichloroethylene , population , environmental health , genotype , confidence interval , toxicology , oncology , genetics , gene , environmental chemistry , biology , pathology , chemistry , paleontology
Background There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants; however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk. Procedure We conducted a case‐only study to evaluate census tract‐level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children's Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the US EPA's 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case‐only odds ratios and 95% confidence intervals (CIs). Results There were 11 significant gene–environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04). Conclusions This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies. Pediatr Blood Cancer 2012;59:605–610. © 2012 Wiley Periodicals, Inc.