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

陈坤; 金明娟; 范春红; 宋亮; 蒋沁婷; 俞维萍; 马新源; 姚开颜

文章摘要

陈坤,金明娟,范春红,宋亮,蒋沁婷,俞维萍,马新源,姚开颜.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[J].中华流行病学杂志,2005,26(9):659-664

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

收稿日期:2004-09-09 出版日期:2014-09-15

DOI：

中文关键词: 肿瘤,结直肠基因多态性细胞色素P450 谷胱甘肽S-转移酶 N-乙酰化转移酶

英文关键词: Colorectal neoplasms Genetic polymorphisms Cytochrome P450 Glutathione S- iransferase N - acetyltransferase

基金项目:国家自然科学基金资助项目(30170828)

作者	单位
陈坤	浙江大学公共卫生学院流行病学与卫生统计学教研室, 杭州 310031
金明娟	浙江大学公共卫生学院流行病学与卫生统计学教研室, 杭州 310031
范春红	浙江大学公共卫生学院流行病学与卫生统计学教研室, 杭州 310031
宋亮	浙江大学公共卫生学院流行病学与卫生统计学教研室, 杭州 310031
蒋沁婷	浙江大学公共卫生学院流行病学与卫生统计学教研室, 杭州 310031
俞维萍	浙江大学公共卫生学院流行病学与卫生统计学教研室, 杭州 310031
马新源	浙江省嘉善县肿瘤防治所, 杭州 310031
姚开颜	浙江省嘉善县肿瘤防治所, 杭州 310031

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中文摘要:

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。

英文摘要:

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 CYPlAl 6235T/C, CYPIA2 734C/A,CYP2E1 -1259G/C, CYP2EI - 1019C/T, GSTM1 and T1 null type,NATl and NAT2 alleles among 140 cases and 343 cancer-free controls. Results The allele frequencies of CYPlAl 6235C,CYP1A2 734A,CYP2EI -1259CXYP2EI -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 CYPiAl 6235CC homozygote was associated with the significant reduction of CRC risk(OR = 0.79,95% Cl： 0 -63-0.99) and in individuals with CYPIA2 734A allele. CYP1A1 62345C allele had the same effect(OR = 0. 53,95 % C/:0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk(OJ? = 4.41,95% Cl ： 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.

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