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目的以自然随访人群为研究对象,研究Ⅰ、Ⅱ相代谢酶基因多态性与结直肠癌(CRC) 易感性的关系。方法采用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)、等位基因特异性PCR(AS-PCR)和多重PCR分析技术,检测140例CRC患者和343名健康对照细胞色素P450氧化酶CYP1A1 6235T/C、CYP1A2 734C/A、CYP2E1-1259G/C和-1019C/T各位点多态性,谷胱甘肽转移酶GST Mu(GSTM1)和GST Theta(GSTT1)缺陷型,以及N-乙酰基转移酶基因NAT1和NAT2各等位基因型分布频率,分析其对CRC易感性的影响。结果等位基因CYP1A1 6235C、CYP1A2 734A、CYP2E1-1259C、CYP2E1-1019T、GSTM1缺陷型、GSTT1缺陷型、NAT1*10和NAT2 Mx (x=1,2,3)的分布频率在病例组依次为31.65%、63.77%、23.02%、32.61%、57.25%、17.39%、26.45%和39.21%,对照组依次为39.85%、66.62%、20.27%、28.61%、55.46%、20.35%、25.22%和39.36%,所有基因型分布均符合Hardy-Weinberg平衡定律。单基因、多基因联合分层分析表明, CYP1A1 6235CC突变纯合型可显著降低CRC风险(OR=0.79,95%CI:0.63～0.99);在携带CYP1A2 734A等位基因个体,CYP1A1 6235C等位基因也可显著降低CRC风险(OR=0.53,95% CI:0.34～0.83);在GSTT1缺陷型个体,GSTM1缺陷型可使机体罹患CRC的风险显著升高(OR= 4.41.95%CI:1.21～16.10)。结论CYP1A1 6235C等位基因、GSTM1和T1缺陷基因型可影响机体对CRC的遗传易感性,前者是CRC的保护因素,后两者可使机体罹患CRC的风险增高。
Objective To investigate the relationship between polymorphisms of Ⅰ and Ⅱ metabolic enzymes and colorectal cancer (CRC) susceptibility in natural follow-up population. Methods Polymerase chain reaction-restriction fragment length polymorphism (RFLP), allele-specific PCR (AS-PCR) and multiplex PCR analysis were used to detect 140 CRC patients and 343 healthy control cytochromes CYP1A2 734C / A, CYP2E1-1259G / C and -1019C / T polymorphisms at the P450 oxidases CYP1A1 6235T / C, glutathione transferase GST Mu (GSTM1) and GST Theta (GSTT1) deficiencies, and N-acetyltransferase gene NAT1 and NAT2 allele distribution frequency, analysis of its impact on susceptibility to CRC. Results The frequencies of alleles CYP1A1 6235C, CYP1A2 734A, CYP2E1-1259C, CYP2E1-1019T, GSTM1 deficiency, GSTT1 deficiency, NAT1 * 10 and NAT2 Mx (x = 1,2,3) were 31.65 %, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the control group, followed by 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% All genotype distributions were in accordance with Hardy-Weinberg equilibrium law. Hierarchical analysis of single gene and multiple genes showed that CYP1A1 6235CC homozygous mutation could significantly reduce the risk of CRC (OR = 0.79, 95% CI: 0.63-0.99); in individuals carrying CYP1A2 734A allele, CYP1A1 6235C allele (OR = 0.53, 95% CI: 0.34-0.83). In GSTT1-deficient individuals, GSTM1 deficiency significantly increased the risk of CRC (OR = 4.41.95% CI: 1.21 ~ 16.10). Conclusion CYP1A1 6235C allele, GSTM1 and T1 defective genotypes may affect the genetic susceptibility of CRC to CRC. The former is a protective factor of CRC. The latter two may increase the risk of CRC.