Influences of Genetic Polymorphisms of Glutathione S-transferase M1 and T1, and N-acetyltransferase 2 on Colorectal Cancer Risk / 대한진단검사의학회지

ABSTRACT

BACKGROUND: Inherited polymorphisms that affect carcinogen metabolism may influence the risk for the development of colorectal cancer. This study was performed to evaluate the potential association between glutathione S-transferase M1 (GSTM1), GSTT1 and N-acetyltransferase 2 (NAT2) polymorphisms and colorectal cancer in Korea. METHODS: The frequencies of GSTM1, GSTT1, and NAT2 polymorphisms were compared between 98 patients with colorectal cancer and age and sex matched 98 healthy controls. GSTM1 and GSTT1 polymorphisms were simultaneously determined by multiplex polymerase chain reaction (PCR) and NAT2 polymorphisms were analyzed by real-time PCR with melting curve analysis. GSTM1 null, GSTT1 null and NAT2 rapid type were considered as risk genotypes. RESULTS: The prevalence of GSTM1 null genotype was 44.9% in the controls, and 58.2% in the cases (odds ratio, OR=1.706, P=0.086). The prevalence of GSTT1 null genotype in the controls and the cases was 48.0% and 54.1%, respectively (OR=1.278, P=0.475). NAT2 rapid type were found in 45.9% of healthy controls and 51.0% of cancer patients (OR=1.227, P=0.568). Relative risk for colorectal cancer increased significantly (P=0.032) as the number of risk genotypes increased. CONCLUSIONS: These results suggest that genetic polymorphisms of GSTM1, GSTT1 and NAT2 have no independent effect on colorectal cancer risk individually, but there exists a dose-response relationship between a combined number of the risk genotypes of GSTM1, GSTT1 and NAT2 and colorectal cancer risk.