Contribution to decreased susceptibility to liver cancer in thais

Abstract

Glutathione S-transferases (GSTs) play important roles in carcinogenic biotransformation processes, which vary among individuals. Polymorphisms of the encoding genes are associated with alteration of detoxification capacity, resulting in a variable risk of cancer development. The present study was performed to determine the effects of polymorphisms in GST (M1, P1, and T1) genes on susceptibility to liver cancer in Thais. We recruited 140 hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients and 280 healthy volunteers for our unmatched case-control based association study. GSTM1 deletion and heterozygous deletion were determined and discriminated by semi-quantitative denaturing high performance liquid chromatography (DHPLC). A polymerase chain reaction - restriction fragment length polymorphisms (PCR-RFLPs) approach was utilized to detect the GSTP1 Ile105Val variant, while the GSTT1 null allele was detected by multiplex PCR. With results for single locus associations, only GSTP1 Ile/Val showed a significant decrease in the risk of liver cancer (OR=0.58; 95% CI: 0.36-0.90; p-value=0.016). GSTP1 (Ile/Val) interacted with the GSTT1 wild type to further decrease susceptibility to liver cancer (OR=0.41; 95% CI: 0.18-0.93; p-value=0.029). Moreover, three locus interactions of GSTP1 (Ile/Val or Val/Val) with either wild type or null alleles of both GSTM1 and GSTT1 decreased risk of liver cancer. In conclusion the GSTP1 null genotype apparently causes decreased risk of liver cancer in Thais. The findings point to GSTP1 Ile105Val as a possible protective allele against liver cancer risk.