Xenobiotics 대사 효소의 다형성과 한국인 대장암 환자의 감수성 유전자에 대한 연구
Genetic Polymorphism of Xenobiotics Metabolizing Enzymes and Individual Susceptible Genes to Colorectal Cancer Patients in Korea
이흥우, 김민수, 정파종, 김현준, 공구, 전호경,
소속 상세정보
이흥우 ( Lee Heung-Woo )
한양대학교 의과대학 외과학교실
김민수 ( Kim Min-Soo )
한양대학교 의과대학 외과학교실
정파종 ( Jung Pa-Jong )
한양대학교 의과대학 외과학교실
김현준 ( Kim Hyun-Jun )
한양대학교 의과대학 병리학교실
공구 ( Kong Gu )
한양대학교 의과대학 병리학교실
전호경 ( Chun Ho-Kyung )
성균관대학교 의과대학 삼성서울병원 외과학교실
KMID : 0356720020180040205
Abstract
Individual susceptibility to cancers may result from several factors including differences in xenobiotics metabolism, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. To determine the frequencies of the genotypes of phase Ⅰ (CYP1A1 and CYP2E1) and phase Ⅱ (GSTM1 and NAT2) metabolizing enzymes and to identify the high-risk genotypes of these metabolic enzymes to colon cancer in Korean, we have analyzed 113 colorectal cancer patients and corresponding age and sex matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In analysis of phase I enzymes, m1/m2, m2/m2 and Val/Val genotypes in CYP1A1 enzyme polymorphisms and C1/C2 genotype in CYP2E1 polymorphism were associated with high relative risks to colorectal cancers (Odds ratio; 1.51, 1.59, 1.76 and 1.38, respectively). Among the phase Ⅱ enzymes polymorphisms, GSTM (-) genotype of GSTM1 enzyme and slow acetylator (S/S) of NAT2 enzyme had 1.48 and 1.34 times of relative risks to colorectal cancers, respectively. In combined genotyping of phase Ⅰ enzymes and GSTM1 polymorphisms, the patients with m1/m2 and GSTM (-), Val/Val and GSTM (-), and C1/C2 and GSTM (-) combined genotypes had
higher relative risk than the patients with each baseline of combined genotypes (Odds ratio; 2.15, 5.81 and 2.20, respectively). In combined genotyping of phase Ⅰ enzyme and NAT2 polymorphisms, the combined genotypes of m1/m2 with slow acetylator and C1/C2 with slow acetylator were more susceptible to colorectal cancer (Odds ratio; 3.5 and 4.5, respectively). These results suggest that the combined genotypes of Val/Val and GSTM (-), m1/m2 and slow acetylator, and C1/C2 and slow acetylator were more susceptible to colorectal cancer in Korean. And genotyping of xenobiotics metabolizing enzymes could be useful for predicting an individual susceptibility to colorectal cancer.
키워드
감수성 유전자;Phase Ⅰ과 Phase Ⅱ 대사효소;유전자분류 PCR-RFLP;대장암
Susceptible gene;Phase Ⅰ and Ⅱ metabolizing ensymes;Genotyping;PCR-RFLP;Colorectal cancer
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