Glutathione S-transferases M1, T1 genotypes and the risk of gastric cancer: a case-control study

Abstract

Aim: Glutathione S-transferases (GSTs) are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione S-transferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTT1 and GSTT1 and gastric cancer.

Methods: A population based case-control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTT1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis.

Results: An increase in risk for gastric cancer was found among carriers of GSTT1 null genotype. The adjusted odds ratio (OR) was 2.63 95% Confidence Interval (95% CI) 1.17-5.88, after controlling for age, gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTT1 null and GSTT1 non-null genotype was significantly higher than in those with both GSTT1 and GSTT1 non-null genotype (OR = 2.77, 95% CI 1.15-6.77). Compared with those subjects who never smoked and had normal GSTT1 genotype, ORs were 1.60 (95% CI:0.62-4.19) for never smokers with GSTT1 null type, 2.33 (95% CI 0.88-6.28) for smokers with normal GSTT1, and 8.06 (95% CI 2.83-23.67) for smokers with GSTT1 null type.

Conclusions: GSTT1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related carcinogenesis of gastric cancer.

Figure 1

Agarose gel electrophoresis of PCR products. 157 bp fragment: GSTM1; 268 bp fragment: β-globin. Lane M: marker; Lanes 4 and 5: GSTM1 null; Lanes 1, 2, 3, 6 and 7: GSTM1 non null.

Figure 2

Agarose gel electrophoresis of PCR products. 480 bp fragment: GSTT1; 268 bp fragment: β-globin. Lane M: marker; Lanes 1, 4, and 6: nun-null; Lanes 2, 3, 5 and 7: GSTT1 null.