title: Maternal variation in EPHX1, a xenobiotic metabolism gene, is associated with childhood medulloblastoma: an exploratory case-parent triad study.
abstract: Common epidemiologic study designs used for evaluating germline genetic determinants of childhood medulloblastoma are often subject to population stratification bias and do not account for maternal genetic effects, a proxy for the intrauterine environment, which may be important in determining etiologic factors for this outcome. The case-parent triad design overcomes these limitations. Therefore, we conducted an exploratory study among 27 childhood medulloblastoma case-parent triads recruited from the Childhood Cancer Epidemiology and Prevention Center at Texas Children's Hospital (Houston, USA) between 2003 and 2010. We assessed 13 single nucleotide polymorphisms (SNPs) in nine xenobiotic detoxification genes, as deficiencies in this pathway may induce brain tumorigenesis. Log-linear modeling was used to assess the association between medulloblastoma and both the offspring (i.e., case) and maternal genotypes of each SNP. In our population, there were no offspring genotypes that were significantly associated with disease risk. However, the maternal EPHX1 rs1051740 genotype (RR = 3.26, P = .01) was associated with medulloblastoma risk. This exploratory study highlights the utility of the case-parent triad design, but these results should be interpreted cautiously due to the limited sample size.
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX.
authors.forename: Darryl
authors.initials: D
authors.lastname: Nousome
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Okcu
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Scheurer
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D009363:Neoplasm Proteins; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human