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

S Liu; J.Y Park; S.P Schantz; J.C Stern; P Lazarus

doi:10.1016/S1368-8375(00)00099-3

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

Journal article

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

S Liu, J.Y Park, S.P Schantz, J.C Stern and P Lazarus

Oral oncology, Vol.37(5), pp.437-445

2001

DOI: https://doi.org/10.1016/S1368-8375(00)00099-3

Handle:

https://hdl.handle.net/2376/115325

PMCID: PMC3715306

PMID: 11377232

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https://doi.org/10.1016/S1368-8375(00)00099-3View

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Abstract

Oral cancer risk

CYP2E1

Genetic susceptibility

Polymorphisms

Cytochrome P450

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.

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Title: Elucidation of CYP2E1 5′ regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer
Creators: S Liu - Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA
J.Y Park - H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA
S.P Schantz - Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
J.C Stern - Department of Otolaryngology, The New York Eye and Ear Infirmary, New York, NY 10003, USA
P Lazarus - H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA
Publication Details: Oral oncology, Vol.37(5), pp.437-445
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: Elsevier Ltd
Identifiers: 99900548078501842
Language: English
Resource Type: Journal article