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
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
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