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

Citation
S. Liu et al., Elucidation of CYP2E1 5 ' regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer, ORAL ONCOL, 37(5), 2001, pp. 437-445
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ORAL ONCOLOGY
ISSN journal
1368-8375 → ACNP
Volume
37
Issue
5
Year of publication
2001
Pages
437 - 445
Database
ISI
SICI code
1368-8375(200107)37:5<437:EOC5'R>2.0.ZU;2-N
Abstract
The CYP2E1 gene, whose protein product plays an important role in the metab olism 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 stud y, we have examined these polymorphisms to elucidate CYP2E1 allelic haploty pe, examining the prevalence of these CYP2E1 alleles in Caucasians and Afri can Americans and their potential role in risk for oral cancer. In addition to the c1 (RsaI[+]/PstI[-]) and c2 (RsaI[-]/PstI[+]) alleles reported in p revious studies, we have identified two new alleles, c3 (RsaI/[+]/Pst[-]) a nd c4 (RsaI[-]/PstI[-]). The prevalence of the c2 and c3 alleles differs be tween racial groups, with African Americans exhibiting a lower prevalence o f the c2 allele (0.003) but a higher prevalence of the c3 allele (0.049) th an 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) ge notype was observed in oral cancer cases as compared to frequency-matched c ontrols in subjects who smoked less than or equal to 24 pack-years (P=0.033 ). No association was observed between CYP2E1 genotype and risk for oral ca ncer in the heavy-smoking group (i.e. > 24 pack-years). Similar trends were observed for both Caucasians and African Americans. These data suggest tha t the cl allele may contribute to increased risk for oral cancer. (C) 2001 Elsevier Science Ltd. All rights reserved.