代谢酶基因多态性与结直肠癌易感性关系的病例对照研究

A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer

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 association between metabolic enzymes polymorphisms and the risk of colorectal cancer（CRC）. Methods Methods of detection used were based on polymerase chain reaction（PCR） including PCR-restriction fragment length polymorphism （PCR-RFLP）, allele specific-PCR （AS-PCR） and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls. Results The allele frequencies of CYP1A 1 6235C, CYP1A2 734A, CYP2E1 -1259C,CYP2E1 -1019T,GSTM1 and T1 null type, NAT1 ＊ 10 and NAT2 Mx（x= 1,2,3） alleles were 31.65%,63.77%,23.02%,32.61%,57.25%,17.39%,26.45% and 39.21% in the case group and 39.85%,66.62%,20.27%,28.61%,55.46%,20.35%,25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk（ OR = 0.79,95 % CI ： 0.63-0.99） and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect（ OR = 0.53, 95 % CI ： 0.34-0.83 ）. However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk（OR=4.41,95% CI： 1.21-16.10）. Conclusion CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.