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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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.
참고문헌 (27)
- "Combined influence of genetic and dietary factors oncolorectal cancer incidence in japanese Americans", 26, pp.101~5 (1999)
- "A pharmacogenetic study to investigate the role of dietary carcinogensin the etiology of colorectal cancer", 23, pp.1839~49 (2002)
- "Glutathione S-transferase polymorphisms and risk of colorectaladenomas", 163, pp.201~6 (2001)
- "A multiplexPCR procedure for polymorphic analysis of GSTM1 and GSTT1 genesin population studies", 107, pp.229~33 (1996)
- "The glutathione S-transferase supergenefamily:regulation of GST and the contribution of the isoenzyme tocancer chemoprotection and drug resistance", 30, pp.445~600 (1995)
- "The human glutathione S-transferase supergene family,its polymorphism,and its effects on susceptibility to lung cancer", 98, pp.87~94 (1992)
- "Relationshipbetween the GSTM1 genetic polymorphism and susceptibility tobladder,breast and colon cancer", 14, pp.1821~4 (1993)
- "Glutathione S-transferase GSTT1 genotypes and susceptibilityto cancer:studies of interactions with GSTM1 in lung,oral,gastricand colorectal cancers", 17, pp.881~4 (1996)
- "and susceptibility to prostate cancer in Northern India", pp.170~3
- "Effects of N-acetyl transferase1 and 2 polymorphisms on bladder cancer risk in Caucasians", 581, pp.97~104 (2005)
- "Molecular genetics and function of NAT1 and NAT2:rolein aromatic amine metabolism and carcinogenesis", 507(6), pp.65~77 (2002)
- "Acetylation genotype and the genetic susceptibility to prostatecancer in a southern European population", 64, pp.246~52 (2005)
- "NAT2 slow acetylator genotype as an important modifierof breast cancer risk", 114, pp.579~84 (2005)
- "Acetylationphenotype in colorectal carcinoma", 47, pp.1466~9 (1987)
- "Polymorphisms of glutathione-S-transferase and arylamine N-acetyltransferaseenzymes and susceptibility to colorectal cancer", 24, pp.3965~70 (2004)
- "Diet,acetylator phenotype,and risk of colorectal neoplasia", 347, pp.1372~4 (1996)
- "Ethnicdistribution of the glutathione transferase Mu 1-1(GSTM1)null genotypein 1473 individuals and application to baldder cancer susceptibility", 15, pp.1077~81 (1994)
- "Ethnic differences in the prevalence of the homozygous deletedgenotype of glutathione S-transferase theta", 16, pp.1243~5 (1995)
- "^Glutathione S-transferasepolymorphisms", pp.7~32 (2000)
- "Slow acetylator mutations in thehuman polymorphic N-acetyltransferase gene in 786 Asians application to metabolic epidemiology", pp.827~34 (1993)
- "Ethnic distribution of slow acetylatormutations in the polymorphic N-acetyltransferase(NAT-2)gene", 4, pp.125~34 (1994)
- "Polymorphismsin GSTP1,GSTM1,and GSTT1 and susceptibility to colorectalcancer", 8, pp.289~92 (1999)
- "Glutathione S-transferase GSTM1 and GSTT1 polymorphismsand colorectal cancer risk:a prospective study", 7, pp.1001~5 (1998)
- "Polymorphism of glutathione S-transferase lociGSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt", 142, pp.97~104 (1999)
- "Analysisof CYP 2E1 and GSTM1 polymorphisms for the determination ofgenetic susceptibility to Korean patients with colon cancer 한국인 대장암 환자의 유전적 감수성 결정을 위한CYP2E1 및 GSTM1 다형성 분석", pp.600 600~10 10
- "Glutathione S-transferase T1 and M1 genotypes innormal mucosa,transitional mucosa and colorectal adenocarcinoma", 84, pp.135~8 (1999)
- "Polyadenylation polymorphism in the acetyltransferase 1gene(NAT1)increases risk of colorectal cancer", 55, pp.3537~42 (1995)
