Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: A case–control study in an Indian population

Abstract

Background: Susceptibility to sporadic colorectal cancer is multifactorial and arises from interactive combinations of allelic variants in low-penetrance genes and relevant environmental risk factors. Genetic polymorphisms in metabolic enzymes as gene susceptibility factors may modify colorectal cancer risk. We evaluated the risk of colorectal cancer associated with respective or combined glutathione S-transferase (GST) polymorphisms and assessed the interactions between genes and environmental factors in a case–control study in an Indian population. Methods: The study included 59 colon and 243 rectal cancer cases, and 291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR-based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms was estimated by calculation of odds ratios (ORs) and confidence intervals (95% CIs) using unconditional logistic regression. Results: The GSTM1 null genotype was found to be associated with a significantly increased rectal cancer risk (OR = 1.55; 95% CI, 1.05–2.30), while the GSTT1 null genotype with a greater risk of colon cancer (OR = 2.15; 95% CI, 1.04–4.32). A substantial increase of both colon (OR = 10.81; 95% CI, 1.11–107.22) and rectal (OR = 4.80; 95% CI, 0.94–35.91) cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1 105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an increased risk for either colon cancer (OR = 4.69; 95% CI, 0.84–23.87) or rectal cancer (OR = 5.68; 95% CI, 1.79–22.16). Furthermore, the combination of GSTM1 null, GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases. Conclusion: Our results suggest that co-exist of GSTM1 null, GSTT1 null and the variant GSTP1 105Val or 114Val allele may be predisposing risk factors for colorectal cancer in Indian population.