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BACKGROUND: Genetic polymorphisms of some metabolizing enzymes, such as glutathione S-transferase M1 ( GSTM1) and N-acetyltransferase 2 ( NAT2), have recently been shown to affect individual susceptibility to various types of cancers. However, the link between the GSTM1 polymorphism and gastric cancer is controversial and there are few studies focusing on the relation between a combination of the two enzyme genotypes and gastric cancer risk.METHODS: Genotypes of GSTM1 and NAT2 were determined by polymerase chain reaction (PCR) or restriction fragment length polymorphism (RFLP) following PCR in 147 Japanese patients with gastric cancer and 112 autopsied Japanese patients without stomach, lung, urinary bladder, or colon cancer.RESULTS: The frequency of the GSTM1 null genotype was significantly increased in the cancer patients (91 individuals; 61.9%) compared with the controls (55 individuals; 49.1%) ( P &lt; 0.05; odds ratio, 1.68). The incidence of patients with the homozygously wild genotype of NAT2 (rapid acetylator) was slightly lower in the cancer group (59 individuals; 40.1%) than in the control group (58 individuals; 51.8%). The proportion of patients with both the GSTM1 gene and homozygously wild genotype of NAT2 was significantly smaller in the cancer group (19 individuals; 12.9%) than in the control group (29 individuals; 25.9%) ( P &lt; 0.05). In addition, in a comparison of four subgroups of gastric cancer which were classified by both the genotype of GSTM1 and the predicted phenotype of NAT2, the number of subjects in the subgroup " GSTM1+/rapid" was significantly smaller than the expected numbers of the other three subgroups ( P &lt; 0.05).CONCLUSION: It is suggested that a combination of GSTM1 and NAT2 decreases the risk of gastric cancer in Japanese patients.

Genotypes of glutathione S-transferase M1 and N-acetyltransferase 2 in Japanese patients with gastric cancer