Genetic polymorphisms of phase I and phase II xenobiotic enzymes in human papillomavirus related lesion and cancer of the uterine cervix

Objective: Other than a major role of human papillomavirus (HPV) infection, exposure to cigarette smoke, estrogen and possibly other carcinogens may be related to the development of cancer. The aim of this study was to investigate whether the polymorphism of CYP1A1, CYP2E1, mEH, and GSTM1 contributes to the risk of invasive cervical cancer (ICC) and the low-grade squamous intraepithelial lesions (LSIL) of the uterine cervix. Materials and Methods: In this study, genetic polymorphisms of xenobiotic metabolizing enzymes CYP1A1, CYP2E1, mEH, and GSTM1, as well as the status of HPV infection were determined in 113 cases with invasive cervical cancer (ICC), 80 cases of low grade squamous intraepithelial lesion (LSIL, the early lesion of HPV infection), as well as in 1:1 age-matched control subjects. Results: As expected, subjects with results positive for HPV had significant risks for LSIL and ICC, with OR (95% CI) of 19.6 (6.9-55.3) and 61.1 (25.3-147.9), respectively. In comparison with the A/A genotype, A/ G or GIG genotype of the CYP1A1 gene showed a protection for ICC, but not for LSIL, with an OR of 0.3 (95% CI of 0.1 -0.9) after adjustment with HPV status. Subjects carrying GSTM1 null genotype were at risk for LSEL (OR=2.5; 95% CI: 1.0-6.3) and ICC (OR: 2.4; 95% CI: 1.0-6.0) after HPV adjustment. The combination of CYP1A1 A/A and GSTM1 null genotype showed a higher risk for ICC (OR of 4.2, 95% CI of 1.4-12.3; p