Association of GSTM1, GSTT1, and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population

Abstract

Objective: The objective of the study was to evaluate the influence of genetic polymorphisms of GSTM1, GSTT1, and GSTM3 on the susceptibility of cervical cancer.

Study design: Blood samples from 150 women with biopsy-confirmed cervical cancer and 168 healthy controls were analyzed by multiplex polymerase chain reaction (PCR) to detect the presence or absence of GSTM1 and GSTT1. Insertion/deletion polymorphism in intron 6 of GSTM3 was determined by PCR.

Results: The frequencies of homozygous GSTM1 null and GSTT1 null genotypes were found to be significantly higher in cancer patients as compared with healthy controls (P = .009, odds ratio [OR] 1.52, 95% confidence interval [CI], 1.1 to 2.0 and P = .0004, OR 2.4, 95% CI: 1.4 to 4.0, respectively). The AB genotype of GSTM3 also conferred higher risk of cancer (P = .053, OR 1.64, 95% CI, 1.0 to 2.6). However, no significant association of at-risk genotypes was observed with any stages of cervical cancer. Interactions among GSTM1 null, GSTT1 null, and AB genotype of GSTM3 resulted in additive predictive risks of cervical cancer. In case-only analysis, carriers of the AA genotype of GSTM3 among tobacco users were at elevated risk of cervical cancer (P = .024, OR 2.1, 95% CI, 1.0 to 4.1) as compared with AB and BB genotypes.

Conclusion: GSTM1 null, GSTT1 null, and GSTM3*AB genotypes may confer higher susceptibility to cervical cancer and cancer risk because at-risk genotypes are additive. Tobacco usage by carriers of GSTM3*AA has enhanced the risk of cervical cancer as compared with nonusers.