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Glutathione S-Transferase M1 및 T1과 N-Acetyltransferase 2다형성이 대장암 발생에 미치는 영향

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

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주제분류병리학

초록

목적 : 발암물질의 대사에 관여하는 유전적 다형성은 대장암발생 위험도에 영향을 미친다. 본 연구에서는 한국인에서 glutathioneS-transferase M1 (GSTM1), GSTT1, N-acetyltransferase 2(NAT2)의 다형성과 대장암과의 잠재적인 관련성을 알아보고자하였다.방법 : 대장암이 판정된 환자 98명과 환자군에 성과 연령을 짝지어 무작위로 뽑은 98명의 정상 대조군을 대상으로 GSTM1,GSTT1, NAT2 다형성의 빈도에 관하여 비교하였다. multiplexpolymerase chain reaction (PCR)을 시행함으로써 GSTM1과GST1 다형성을 동시에 분석하였고, NAT2 유전자형을 분석하기 위해 real-time PCR 시스템의 melting curve 분석법을 시행하였다. GSTM1 null genotype, GSTT1 null genotype 그리고NAT2 rapid type을 risk genotype으로 간주하였다. 결과 : 대장암 환자의 58.2%와 정상 대조군의 4 4.9%에서GSTM1 null genotype을 나타냈으며(odds ratio, OR=1.706,P=0.086), 대장암 환자의 54.1%와 정상 대조군의 48.0%에서GSTT1 null genotype을 보였다(OR=1.278, P=0.475). NAT2rapid type은 대장암 환자의 51.0%와 정상 대조군의 45.9%에서나타났다(OR=1.227, P=0.568). Risk genotype의 개수가 증가할수록 대장암 발생 위험도가 증가하는 것으로 나타났다(P=0.032). 결론 : GSTM1, GSTT1, NAT2 유전자의 다형성은 개별적으로는 대장암의 위험도를 높이는데 기여하지 않았지만, GSTM1, GSTT1, NAT2 위험유전형의 개수와 대장암 위험도간에는 양-반응 관계가 성립된다고 볼 수 있다.

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.

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