Elucidation of CYP2E1 5′ regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer

• Published in: Oral oncology Vol. 37; no. 5; pp. 437 - 445
• Main Authors: Liu, S, Park, J.Y, Schantz, S.P, Stern, J.C, Lazarus, P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2001; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Alcohol Drinking - adverse effects; Alleles; Biological and medical sciences; Black People - genetics; Case-Control Studies; CYP2E1; CYP2E1 protein; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P450; Deoxyribonucleases, Type II Site-Specific - genetics; Epidemiologic Methods; Female; Genetic Predisposition to Disease; Genetic susceptibility; Haplotypes - genetics; Humans; Male; Medical sciences; Middle Aged; Mouth Neoplasms - genetics; Oral cancer risk; Otorhinolaryngology. Stomatology; Polymorphism, Genetic; Polymorphisms; PstI gene; Risk Factors; RsaI gene; Sialyltransferases - genetics; Smoking - adverse effects; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; White People - genetics; Oral cancer risk; CYP2E1; Genetic susceptibility; Polymorphisms; Cytochrome P450; Human; Squamous cell carcinoma; Stomatology; Etiopathogenesis; Malignant tumor; Polymerase chain reaction; Oral cavity; Restriction fragment length polymorphism; Pstl restriction enzyme; Genetics; Oral cavity disease; Molecular biology; RsaI restriction enzyme; Polymorphism
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/S1368-8375(00)00099-3

The CYP2E1 gene, whose protein product plays an important role in the metabolism of various carcinogens, exhibits two polymorphisms recognized by the restriction enzymes RsaI and PstI in its transcriptional regulatory region that have been previously implicated in cancer susceptibility. In this study, we have examined these polymorphisms to elucidate CYP2E1 allelic haplotype, examining the prevalence of these CYP2E1 alleles in Caucasians and African Americans and their potential role in risk for oral cancer. In addition to the c1 ( RsaI[+]/ PstI[−]) and c2 ( RsaI[−]/ PstI[+]) alleles reported in previous studies, we have identified two new alleles, c3 ( RsaI[+]/ PstI[+]) and c4 ( RsaI[−]/ PstI[−]). The prevalence of the c2 and c3 alleles differs between racial groups, with African Americans exhibiting a lower prevalence of the c2 allele (0.003) but a higher prevalence of the c3 allele (0.049) than Caucasians (0.031 for c2 and 0.004 for c3). Of the 570 subjects screened in this study, the c4 allele was observed in one subject, a Caucasian case with the (c4/c4) genotype. A significant increase in the CYP2E1 (c1/c1) genotype was observed in oral cancer cases as compared to frequency-matched controls in subjects who smoked ⩽24 pack-years ( P=0.033). No association was observed between CYP2E1 genotype and risk for oral cancer in the heavy-smoking group (i.e. > 24 pack-years). Similar trends were observed for both Caucasians and African Americans. These data suggest that the c1 allele may contribute to increased risk for oral cancer.