Genetic Polymorphism of Xenobiotics Metabolizing Enzymes and Individual Susceptible Genes to Colorectal Cancer Patients in Korea

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 polymorphi(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.