mEH is a critical biotransformation enzyme that catalyzes the conversion of xenobiotic epoxide substrates into more polar diol metabolites: it is also capable of inactivating a large number of structurally different molecules. Two polymorphisms affecting enzyme activity have been described in the exon 3 and 4 of the mEH gene. The hypothesis of this study is that inherent genetic susceptibility to a primary brain tumor is associated with mEH gene polymorphisms. The polymorphisms of the mEH gene were determined with PCR-RFLP techniques and 255 Turkish individuals. Our results indicate that the frequency of the mEH exon 4 polymorphism (in controls) is significantly higher than that of primary brain tumor patients (OR = 1.8, 95% CI = 1.0–3.4). This report, however, failed to demonstrate a significant association between mEH exon 3 polymorphism and primary brain tumor susceptibility in this population. Analysis of patients by both histological types of primary brain tumor and gene variants showed no association, although analysis of family history of cancer between cases and controls showed a statistically significant association ( , ). Our results marginally support the hypothesis that genetic susceptibility to brain tumors may be associated with mEPHX gene polymorphisms. 1. Introduction In recent years, genetic polymorphism in a variety of xenobiotic-metabolizing enzymes (phase I and II enzymes) has been studied extensively. In general, these polymorphisms do not always lead to changes in protein expression and catalytic activities. However, the gene mutations cause alterations in expression and function of the enzymes. For this reason, several polymorphic genes, encoded for enzymes involved in phase I and II reactions, partially explain individual susceptibility to cancer. One of the enzymes is mEH, which catalyzes xenobiotic biotransformation in mammalian tissues and supports detoxification capability of the organism [1]. The mEH (EPHX1 EC 3.3.2.3) is a smooth endoplasmic reticulum enzyme that catalyzes the hydrolysis of epoxides into trans-dihydrodiols and is responsible for the detoxification of PAH [2, 3]. Two variant EPHX1 alleles have been associated with altered mEH activity, which is a substitution of histidine for tyrosine at residue 113 (exon 3 polymorphism); this decreases mEH activity by approximately 40%, whereas substitution of arginine for histidine at residue 139 (exon 4 polymorphism) increases enzyme activity by approximately 25% [4]. These polymorphisms also tend to affect the stability of the mEH protein. An epoxide is a three-membered
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