Genetic Polymorphisms of ADH1C and CYP2E1 and Risk of Oral Squamous Cell Carcinoma

Abstract

Several studies have suggested that the metabolism of alcohol is modulated by the polymorphisms in genes encoding ethanol-metabolizing enzymes, including alcohol dehydrogenase 1C, ADH1C, and cytochrome P450-dependent monooxygenase, CYP2E1. Genetic polymorphisms of ethanol-metabolizing enzymes may affect individual susceptibility to oral cancer. The purpose of this study was to investigate the associations between ADH1C and CYP2E1 gene polymorphisms with oral squamous cell carcinoma in an ethnically homogeneous Caucasian population. Case-control study. Serbian national general hospital. The study was conducted on 123 oral cancer patients and a control group of 177 individuals of the Caucasian race and the same ethnicity, matched in age and gender, without previous cancer history. The control group consisted of 120 population-based and 57 hospital-based controls of heavy-drinking individuals. Genetic polymorphisms of ADH1C SspI, ADH1C HaeIII, CYP2E1 RsaI, and CYP2E1 Ins were determined by the polymerase chain reaction and restriction fragment length polymorphisms. After adjustment by potential confounders, the significant increase of oral cancer risk, independent of alcohol drinking, was observed in individuals with the variant ADH1C SspI*2/*2 genotype (odds ratio, 3.029; P = .014) and in combined ADH1C SspI*1/*2 and ADH1C SspI*2/*2 genotypes (odds ratio, 2.605; P = .002), compared to the ADH1C*1/1* wild type. The association of other polymorphisms under study was not observed. This study suggested that the ADH1C SspI polymorphism could play a significant role in the etiology of oral cancer, whereas ADH1C HaeIII, CYP2E1 RsaI, and CYP2E1 Ins could have minor influence.