The
glutathione S-transferase (
GSTs) are polymorphic supergene family of detoxification
enzymes that are involved in the metabolism of numerous potential
carcinogens. Several allelic variants of polymorphic
GSTs show impaired
enzyme activity and are suspected to increase the susceptibility to various
cancers. To find out the association of GST variants with risk of
gallbladder cancer, the distribution of polymorphisms in the GST family of genes (GSTT1, GSTM1, GSTP1, and GSTM3) were studied in 106
cancer patients and 201 healthy controls. Genotypes were analysed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). The frequencies of GSTM1 null and GSTM3*BB genotypes did not differ between patients and controls. The overall frequency of GSTT1 null was lower in cases as compared with controls (p=0.003, Odds ratio (OR) = 0.2, 95% confidence interval (CI), 0.1-0.6). After sex stratification, the GSTT1 null frequency was reduced only in female patients (p=0.008, OR = 0.2, 95% CI = 0.1-0.6). However, the GSTP1,
ile/val genotype and the val allele were significantly higher in cases than controls (p=0.013, OR = 1.9, 95% CI = 1.1-3.1; p=0.027, OR = 1.5, 95% CI = 1.0-2.1), respectively. To study gene-gene interactions, a combined risk of
gallbladder cancer due to
ile/val or
val/val were calculated in combination with null alleles of GSTM1 and GSTT1 or the *B allele of GSTM3, but there was no enhancement of risk.
Gallstones were present in 57.5% of patients with
gallbladder cancer, but there were no significant differences between allelic/genotype frequencies of the studied GST genes polymorphisms between patients with or without
gallstones. To best of our knowledge, this is the first paper showing
ile/val genotypes and val allele of GSTP1 to be associated with higher risk of
gallbladder cancer.