An exploratory case-only analysis of gene-hazardous air pollutant interactions and the risk of childhood medulloblastoma

Lupo, PJ; Lee, LJ; Okcu, MF; Bondy, ML; Scheurer, ME

HERO ID

2128169

Reference Type

Journal Article

Year

2012

Language

English

PMID

22389292

HERO ID 2128169
In Press No
Year 2012
Title An exploratory case-only analysis of gene-hazardous air pollutant interactions and the risk of childhood medulloblastoma
Authors Lupo, PJ; Lee, LJ; Okcu, MF; Bondy, ML; Scheurer, ME
Journal Pediatric Blood & Cancer
Volume 59
Issue 4
Page Numbers 605-610
Abstract <strong>BACKGROUND: </strong>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.<br /><br /><strong>PROCEDURE: </strong>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).<br /><br /><strong>RESULTS: </strong>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).<br /><br /><strong>CONCLUSIONS: </strong>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.
Doi 10.1002/pbc.24105
Pmid 22389292
Wosid WOS:000307386300003
Url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864960881&doi=10.1002%2fpbc.24105&partnerID=40&md5=170766dff39f775b8b3c1793869b92bd
Is Certified Translation No
Dupe Override No
Comments Journal: Pediatric blood & cancer ISSN: 1545-5017
Is Public Yes
Language Text English
Keyword childhood medulloblastoma and primitive neuroectodermal tumor; chlorinated solvents; detoxification genes; DNA repair genes; hazardous air pollutants