Mt. Goodman et al., CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population, GYNECOL ONC, 81(2), 2001, pp. 263-269
Objective. In this investigation, we explored the hypothesis that genetic p
olymorphisms in the cytochrome P4501A1 (T3801C) and glutathione S-transfera
se classes mu and theta (GSTM1 and GSTT1) gene deletions promote the develo
pment of cervical dysplasia by moderating the activation and detoxification
of polycyclic hydrocarbons and other compounds that influence oxidative st
ress and DNA adduct formation,
Methods. A multiethnic, case-control study of 131 women with biopsy-confirm
ed cervical squamous intraepithelial lesions (SIL) and 180 controls with cy
tologically normal cervical (Pap) smears was conducted between 1992 and 199
6 in Honolulu, Hawaii. We collected in-person interviews, a blood sample to
extract genomic DNA, and an exfoliated cervical cell sample to determine t
he presence and type of human papillomavirus (HPV) using PCR dot-blot hybri
dization, Genotyping for the CYP1A1 MspI allelic variant and deletion of th
e GSTM1 and GSTT1 gene loci followed a PCR method.
Results. Women who were homozygous, but not heterozygous, for the CYP1A1 Ms
pI variant allele were at significantly increased risk of cervical SIL (odd
s ratio (OR) = 3.4; 95% confidence interval (CI) = 1.1-10.7) compared to wo
men who were homozygous for the wild-type allele, Subjects with the GSTM1 n
ull genotype had a nonsignificant elevated risk of cervical SIL (OR = 1.6;
95% CI = 0.8-3.0) compared to women with the gene present. No difference in
the risk of cervical disease was associated with the GSTT1 null genotype,
The combination of the CYP1A1 homozygous variant and the GSTM1 null genotyp
es increased the odds ratio for cervical SIL to 5.1 (95% CI = 1.3-20.7). Th
ere was no evidence for an interaction between genotype and exposure to tob
acco smoke, alcohol drinking, or HPV DNA positivity.
Conclusions. These findings, although based on a small number of subjects,
suggest that the CYP1A1 MspI polymorphism may be a susceptibility factor fo
r early, premalignant changes in the cervical epithelium. (C) 2001 Academic
Press.