Maternal Variation inEPHX1, 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, TX) 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=0.01) 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.

Assessment of interaction between maternal polycyclic aromatic hydrocarbons exposure and genetic polymorphisms on the risk of congenital heart diseases

“…One previous study did not find an association between the maternal CYP1A1 rs1048943 polymorphism and the risk of non-syndromic oral cleft 49 . Another study did not find an association between the maternal CYP1B1 rs1056836 polymorphism and childhood medulloblastoma 50 . One study in 2006 showed that the maternal CYP1B1 rs1048943 polymorphism was associated with first-trimester miscarriage and that it might also modify the risk of first-trimester miscarriage among coffee drinkers 51 .…”

Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

“…In spite of the potential importance of this mechanism in the etiology of CBTs, few assessments of maternal genetic effects have been performed. To our knowledge, there is only one small report that used a case parent triad study design (33) of the role maternal variation in xenobiotic detoxification genes and the risk of childhood MB (34) where it was reported that the maternal EPHX1 rs1051740 genotype was associated with MB risk (RR=3.26; 95% CI 1.12–9.53). Larger studies are needed to explore the role of maternal genetic effects in CBT susceptibility.…”

LncRNA CDKN2BAS rs2157719 genetic variant contributes to medulloblastoma predisposition

“…[5][6][7] Among these loci, a number of original and novel single nucleotide polymorphisms (SNPs) were found to be associated with glioma risk in Chinese populations, including 9p21.3 long non-coding RNA (lncRNA) CDKN2BAS rs2157719 genetic variant. 8 However, few studies focusing on revelation of medulloblastoma susceptibility SNPs have been reported, [9][10][11] which may be a result of difficulties in recruiting a sufficient number of medulloblastoma patients and collecting their DNA samples. Therefore, it is still largely unknown how genetic polymorphisms are involved in the etiology of medulloblastoma.…”