ABSTRACT. Glutathione S-transferase (GST) is an important member of phase II metabolic enzymes; GSTM1, GSTT1, and GSTP1 belong to three subfamilies of the GST enzyme. Polymorphisms in GSTM1, GSTT1, and GSTP1 could affect detoxification processes, and increase individuals' susceptibility to cancers. We aimed to investigate the association between GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of gastric cancer in a Chinese population. In addition, we also examined the effect of gene-environmental interactions, and their effect on risk of this cancer. Between July 2013 and June 2015, we recruited 242 gastric cancer patients and 396 healthy controls for our study. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to characterize genetic polymorphisms in GSTM1, GSTT1, and GSTP1. We observed that the Val/Val genotype of GSTP1 was associated with increased risk of gastric cancer when compared with the Ile/Ile genotype (OR = 3.19, 95%CI = 1.84-5.56). Moreover, the Val allele of GSTP1 was associated with higher susceptibility to gastric cancer as compared with the Ile allele (OR = 1.52, 95%CI = 1.19-1.93). However, GSTM1 and GSTT1 polymorphisms did not affect the development of gastric cancer. In conclusion, our study indicated that GSTP1 Ile105Val, but not GSTM1 and GSTT1 polymorphisms, was associated with risk of gastric cancer.

Gastric cancer is the fourth commonly diagnosed cancer and the second most frequent cause of cancer death worldwide. Genetic variations in ADH1B and ALDH2 may alter the function and activity of the corresponding enzymes, leading to differences in acetaldehyde exposure between drinkers. Cytochrome P4502E1 (CYP4502E1) is a phase I enzyme that plays an important role in metabolizing nitrosamine compounds and the bioactivation of procarcinogens. During the period of July 2013 to July 2015, 246 patients and 274 controls were enrolled from the First Affiliated Hospital of Jinan University. In the codominant model, the AA genotype of ALDH2 Glu487Lys significantly elevated the risk of gastric cancer in comparison with the GG genotype of ALDH2 Glu487Lys. In the recessive model, the AA genotype of ALDH2 Glu487Lys significantly increased the risk of gastric cancer compared to the GG+GA genotype (OR = 2.34 95%CI = 1.02-5.70). We found in the codominant model that individuals harboring the C2/C2 genotype of CYP4502E1 had a higher risk of developing gastric cancer than those with the C1/C1 genotype. In addition, in the recessive model, we found that the C2/C2 genotype correlated with an elevated risk of gastric cancer in comparison with the C1/C1+C1/C2 genotype (OR = 4.90, 95%CI = 2.04-13.51). However, no significant relationship was measured between ADH1B Arg47His and gastric cancer risk. In summary, the results of our study indicate that ALDH2 Glu487Lys and CYP4502E1 polymorphisms could be risk factors for the development of gastric cancer in the Chinese population.