Effect of the Genetic Polymorphism of N-acetyltransferase 2 and Diet on the Carcinogenesis of Gastric Cancer in Koreans

PURPOSE: According to the recent studies on the carcinogenic factors of gastric cancer in Koreans, dietary factors, such as stew, roasted fish, and fish boiled in soy with spices, salted foods, as well as smoking, might be risk factors of gastric cancer. N-acetyltransferase 2 (NAT2) is an enzyme that plays a role in the reduction of the toxicity of various carcinogens. There is a possibility that the genetic polymorphism of NAT2 might change a subject's susceptibility to gastric cancer. The aim of this study was to examine the effects of diet, the genetic polymorphism of NAT2 and their interaction on the risk of gastric cancer in Koreans. METHODS: The subjects of this case-control study were 214 gastric cancer patients, and 214 controls, who were admitted at the Chungbuk National or Eulji University Hospitals. Each subject was directly interview, by an experienced interviewer, with a structured questionnaire. A NAT2 genetic polymorphism analysis was performed, with a PCR-RFLP technique, and the data analyzed using the PC-SAS software package. RESULTS: Increased intakes of makkoli, soybean paste stew, kimchi and ggakdugi, soy milk, chicken boiled with rice and boiled chicken were all associated with an increased risk of gastric cancer, whereas those of fermented soybean stew, Welsh onion or leek, onions, peaches, chestnuts or gingko nuts, fatsia shoots, raw fish, salted seafood and laver were all associated with a decreased risk of gastric cancer. The odds ratio (95% confidence interval) for gastric cancer for the rapid acetylators was 1.64 (1.12, 2.41), which was statistically significant. With respect to the rapid acetylators, makkoli, kimchi and soy milk were significant risk factors, and Welsh onion/leek and onions were protective factors for gastric cancer. Whereas, soybean paste stew was a risk factor of gastric cancer with the slow or intermediate acetylators. CONCLUSION: These results suggest the genotype of a rapid acetylation is a risk factor of gastric cancer, and the effects of diet on the risk of gastric cancer vary according to the genotype of the NAT2 enzyme.

A case-control study on the effects of the genetic polymorphisms of N-acetyltransferase 2 and glutathione S-transferase mu and theta on the risk of bladder cancer / 예방의학회지

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which reduce the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTM1) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% for the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity(x(2) trend=l.18, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls (x(2)=5.21, P-value<0.05), and the odds ratio (95% CI) was 2.23 (l.12 - 4.56). GSTT1 deletion, the rate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history, turned out to be insignificant as a risk factor of bladder cancer (OR=l.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: l.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may, be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.