Polymorphism at GSTM1 and CYP2D6 gene loci and modulation of oral cancer risk

Abstract

In this study, the link between polymorphisms at GSTMI and CYP2D6 gene loci and individual susceptibility to oral cancer was analysed using blood samples from 150 patients with cancer of the buccal mucosa and 200 controls matched for age and sex. DNA extracted from white blood cells was subjected to polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis for detection of GSTM1 and CYP2D6 genotypes. The percentage of GSTM1 null individuals was significantly higher in oral cancer patients than in controls (42% vs 23%; p<0.001, odds ratio 2.11, 95% C.I 1.34 - 3.33). Comparative analysis of the CYP2D6 intron 3 - exon 4 polymorphism revealed that the frequencies of the homozygous normal (+/+), heterozygous (+/-), and homozygous mutant (-/-) genotypes were similar in oral cancer patients and controls. However, in combinational analysis the frequency of the GSTM1 null and CYP2D6 +/+ genotype was found to be higher in the cancer patients than in controls (38% vs 16%). The findings shown that individuals with the GSTM1 null allele and those with the combined GSTM1 null and CYP2D6 +/+ genotype are at a higher risk of developing tobacco related oral cancer.