Association of Glutathione S-transferase Gene Polymorphisms With Hepatocellular Carcinoma in Patients From Maharashtra, India

Background: Hepatocellular carcinoma (HCC) is a major global health burden with high mortality. Genetic variations in detoxification enzymes, particularly glutathione S-transferases (GSTs), may influence predisposition to HCC. This population-specific study investigates the relationship between GST gene polymorphisms and the occurrence of HCC in India. Methods: A case-control study was conducted involving 380 individuals (190 confirmed HCC patients and 190 age- and gender-matched healthy controls) from India. Genotyping for GSTM1 (625 bp and 215 bp) and GSTT1 variants was performed using polymerase chain reaction (PCR), while the GSTP1 Ile105Val (A→G) polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Associations between genotypes and the occurrence of HCC were evaluated using the chi-square test and odds ratio (OR) with a 95% confidence interval (CI); a p-value of ≤0.05 was considered statistically significant. Results: The GSTT1 (480 bp) null genotype exhibited a statistically significant positive association with the occurrence of HCC (OR=2.681, 95% CI=1.73-4.14; p<0.0001). In contrast, the GSTM1 (215 bp) null genotype demonstrated a significant negative association with the occurrence of HCC (OR=0.135, 95% CI=0.072-0.25; p<0.0001). Similarly, the GSTM1 (625 bp) null genotype also showed a significant negative association with the occurrence of HCC (OR=0.5476, 95% CI=0.364-0.825; p=0.004). GSTP1 heterozygous (adjusted OR=0.517; 95% CI: 0.124-2.15; p=0.364) and variant (adjusted OR=1.28; 95% CI: 0.3-5.49; p=0.737) genotypes showed no significant association with HCC risk after adjustment for confounding factors. Conclusion: The findings indicate that the GSTT1 (480 bp) null genotype is significantly associated with increased susceptibility to HCC in the Maharashtrian population. In contrast, GSTM1 null genotypes (215 bp and 625 bp) appear to confer a protective effect. GSTP1 polymorphism was not significantly associated with HCC risk after adjustment.