Abstract
Microsomal epoxide hydrolase (EPHX1) is involved in the activation and detoxification of exogenous chemicals. Genetic polymorphisms in EPHX1 have been associated with the development of leukemia. To investigate an association between single-nucleotide polymorphisms (SNPs) of EPHX1 and risk factors for childhood acute lymphoblastic leukemia (ALL) in Korean children, we genotyped two SNPs, Tyr113His (rs1051740) and His139Arg (rs2234922) in 185 childhood ALL cases and 536 healthy controls. Genotyping for these two SNPs was performed by simplex pyrosequencing assay and high-resolution melt analysis, respectively. We found that the Tyr113His genotype was associated with a decreased risk of childhood ALL (odds ratio, OR = 0.64, 95% confidence interval, CI = 0.43 - 0.93; p = 0.02). There was no association between His139Arg and the combined genotypes and the risk of childhood ALL. These results suggest that the EPHX1 113TyrHis genotype may protect against leukemogenesis in childhood.
Highlights
Childhood acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, representing nearly one-third of all pediatric cancers [1]
EPHX1 113Tyr/His and the combined Tyr/His and His/His genotypes were associated with a decreased risk for childhood ALL (ORTC = 0.64, p = 0.02; ORTC+CC = 0.68, p = 0.03)
No association was found between the His139Arg polymorphism and the risk of childhood ALL
Summary
Childhood acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, representing nearly one-third of all pediatric cancers [1]. Childhood ALL is caused by multiple factors, including genetic disorders, exposure to radiation, and immune dysfunction [2] [3] Environmental factors, such as pesticides, household chemical exposure, and parental smoking and alcohol use, have been associated with childhood cancers, including childhood ALL [3]-[5]. These factors are detoxified by drug-metabolizing enzymes, through phase I and II metabolism. Many studies have suggested that genetic polymorphisms in the drug-metabolizing enzymes play a role in susceptibility to childhood ALL [6]-[9]. The 113His allele in exon 3 decreases enzyme activity by 40% and is called the “slow” allele, whereas the 139Arg allele in exon 4 increases enzyme activity in vitro by 25% and is referred to as the “fast” allele [16]
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