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

Abstract

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].Chinese journal of Epidemiology,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

Received:September 09, 2004

DOI：

KeyWord: 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

English Key Word: Colorectal neoplasms Genetic polymorphisms Cytochrome P450 Glutathione S- iransferase N - acetyltransferase

FundProject:国家自然科学基金资助项目(30170828)

Author Name	Affiliation
CHEN Kun	Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health,Hangzhou 310031,China
JIN Ming-juan	Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health,Hangzhou 310031,China
FAN Chun-hong	Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health,Hangzhou 310031,China
SONG Liang	Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health,Hangzhou 310031,China
JIANG Qin-ting	Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health,Hangzhou 310031,China
YU Wei-ping	Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health,Hangzhou 310031,China
MA Xin-yuan	浙江省嘉善县肿瘤防治所, 杭州 310031
YAO Kai-yan	浙江省嘉善县肿瘤防治所, 杭州 310031

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Abstract:

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。

English Abstract:

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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