修复基因ERCC1多态性与肝癌易感性的关系
摘要
目的
探讨修复基因ERCC1多态性与肝癌易感性的关系,及ERCC1基因多态和环境因素的交互作用对肝癌发生的影响。
方法
采用1∶1配对的病例对照研究,病例来自福州市各大医院经病理组织切片确诊为肝癌的新发病例(283例),对照选择与病例在性别、年龄、民族和居住地相匹配的同期入院的非肿瘤患者(283例)。采用统一编制的调查表进行问卷调查。采用PCR-RFLP法对调查对象的血标本进行ERCC1基因多态检测。采用条件Logistic回归方法分析基因、环境、基因-环境在肝癌发生中的作用,计算相对危险度(OR)及其95%CI。全部数据分析采用SPSS13.0软件。
结果
1、1∶1配对的病例对照研究结果显示:肝癌的主要危险因素:吸烟总量>248200支(OR=3.543,95%CI=1.605～7.819),喜食猪油(OR=4.499,95%CI=1.629～12.424),喜食腌制食品(OR=9.006,95%CI=3.047～26.622),食用霉变食物史(OR=6.356,95%CI=1.128～35.803),一级亲属肝癌史(OR=3.088,95%CI=1.114～8.562),乙肝肝炎史(OR=19.069,95%CI=5.496～66.164),家庭生活不和谐(OR=2.000, 95%CI=1.346～2.970)。其中有乙肝肝炎史为肝癌的第一危险因素。肝癌的保护因素:月茶消费量>300g(OR=0.229, 95%CI=0.068～0.766)。
2、ERCC1基因多态性与肝癌易感性的研究结果显示:病例组和对照组ERCC1-4533野生型纯合子(G/G)、杂合子(G/A)、突变型纯合子(A/A)分布有统计学意义(χ2=19.537, P<0.05),其杂合型与突变型与肝癌易感性显著相关,OR杂=1.675(95%CI:1.165～2.408),OR突=5.218(95%CI:1.949～13.956)。病例组和对照组ERCC1-8092野生型纯合子(C/C)、杂合子(C/A)、突变型纯合子(A/A)分布有统计学意义(χ2=55.334,P<0.05),其杂合型与突变型与肝癌易感性显著相关,OR杂=2.625(95%CI:1.727～3.990),OR突=8.254(95%CI:3.819～17.837)。
3、基因-环境因素之间交互作用研究结果显示:ERCC1-8092基因多态性与吸烟存在交互作用(OR=99.699,95%CI =5.239～297.133),未发现ERCC1-4533基因多态性与环境因素存在交互作用。
结论
ERCC1基因4533位点和8092位点多态可能与肝癌遗传易感有关。吸烟总量,喜食猪油,喜食腌制食品,食用霉变食物史,一级亲属肝癌史,乙肝肝炎史,家庭生活不和谐是肝癌的危险因素,有乙肝肝炎史为肝癌的第一危险因素。饮茶是肝癌的保护因素。ERCC1-8092基因多态性与吸烟存在交互作用,使得肝癌发生风险明显增加。
Objective
The study intended to investigate the association between genetic polymorphism of repair gene ERCC1 and susceptibility to hepatoma, and the gene-environmental interaction in etiology of hepatoma.
Materials & methods
Using 1:1 matched case-control study, we have identified 283 hepatoma patients with pathology diagnosis from big hospitals during the periods in Fuzhou city. A total of 283 controls without history of malignant tumor were selected during the same period and matched to each case by gender, age, nationality and inhabited areas. The constructed questionnaires were administered, and the geneotyping of ERCC1 was examined with PCR-RFLP analysis.Conditional logistic regression was used to analyze the role of environmental factors, gene, gene-environmental interaction in the progress of hepatoma, and to calculate odds ratios and 95% confidence intervals. All the calculations and statistics were performed with the computer program, SPSS Version 13.0.
Results
1.Multivariate conditional logistic regression analysis showed that tobacco smoking amount (OR=3.543,95%CI=1.605～7.819),eating lard (OR=4.499, 95%CI= 1.629～12.424),eating pickled food (OR=9.006,95%CI=3.047～26.622),eating moldy food(OR=6.356,95%CI=1.128～35.803),hepatoma history of first degree relative(OR=3.088,95%CI=1.114～8.562),hepatitis B (OR=19.069,95%CI=5.496～66.164),disharmony of family life(OR=2.000, 95%CI=1.346～2.970) were the risk factors of hepatoma cancer; while drinking tea (OR=0.229, 95%CI=0.068～0.766) was the protective factor of hepatoma.Hepatitis B was the greatest risk factor of hepatoma.
2. The distribution of ERCC1-4533 wild-type homozygote(G/G)、heterozygote(G/A)and mutant homozygote(A/A)in hepatoma cases and controls was significant difference(χ2=19.537, P<0.05), heterozygote and mutant homozygote had a increased risk of hepatoma (OR杂=1.675,95%CI:1.165～2.408;OR突=5.218,95%CI:1.949～13.956) compared to wild-type homozygote.
The distribution of ERCC1-8092 wild-type homozygote(C/C)、heterozygote(C/A)and mutant homozygote(A/A)in hepatoma cases and controls was significant difference(χ2=55.334 , P<0.05), heterozygote and mutant homozygote had a significant increased risk of hepatoma (OR杂=2.625,95%CI:1.727～3.990;OR突=8.254,95%CI:3.819～17.837) compared to wild-type homozygote.
3.The analysis of gene-environment interaction showed that tobacco smoking amount appeared interaction with genetic polymorphism of ERCC1-8092.No obvious interaction was observed between genetic polymorphism of ERCC1-4533 and the risk factors of hepatoma. Conclusion
The gene polymorphism of ERCC1-4533,ERCC1-8092 was possibly susceptible to hepatoma. Tobacco smoking amount, eating lard, eating pickled food, eating moldy food , hepatoma history of first degree relative, hepatitis B, disharmony of family life were the risk factors for hepatoma; while drinking tea was regarded as the protective factor to hepatoma.Hepatitis B was the greatest risk factor of hepatoma.There was interaction between tobacco smoking amount and genetic polymorphism of ERCC1-8092,that would aggravate the risk of suffering from hepatoma.
探讨修复基因ERCC1多态性与肝癌易感性的关系,及ERCC1基因多态和环境因素的交互作用对肝癌发生的影响。
方法
采用1∶1配对的病例对照研究,病例来自福州市各大医院经病理组织切片确诊为肝癌的新发病例(283例),对照选择与病例在性别、年龄、民族和居住地相匹配的同期入院的非肿瘤患者(283例)。采用统一编制的调查表进行问卷调查。采用PCR-RFLP法对调查对象的血标本进行ERCC1基因多态检测。采用条件Logistic回归方法分析基因、环境、基因-环境在肝癌发生中的作用,计算相对危险度(OR)及其95%CI。全部数据分析采用SPSS13.0软件。
结果
1、1∶1配对的病例对照研究结果显示:肝癌的主要危险因素:吸烟总量>248200支(OR=3.543,95%CI=1.605～7.819),喜食猪油(OR=4.499,95%CI=1.629～12.424),喜食腌制食品(OR=9.006,95%CI=3.047～26.622),食用霉变食物史(OR=6.356,95%CI=1.128～35.803),一级亲属肝癌史(OR=3.088,95%CI=1.114～8.562),乙肝肝炎史(OR=19.069,95%CI=5.496～66.164),家庭生活不和谐(OR=2.000, 95%CI=1.346～2.970)。其中有乙肝肝炎史为肝癌的第一危险因素。肝癌的保护因素:月茶消费量>300g(OR=0.229, 95%CI=0.068～0.766)。
2、ERCC1基因多态性与肝癌易感性的研究结果显示:病例组和对照组ERCC1-4533野生型纯合子(G/G)、杂合子(G/A)、突变型纯合子(A/A)分布有统计学意义(χ2=19.537, P<0.05),其杂合型与突变型与肝癌易感性显著相关,OR杂=1.675(95%CI:1.165～2.408),OR突=5.218(95%CI:1.949～13.956)。病例组和对照组ERCC1-8092野生型纯合子(C/C)、杂合子(C/A)、突变型纯合子(A/A)分布有统计学意义(χ2=55.334,P<0.05),其杂合型与突变型与肝癌易感性显著相关,OR杂=2.625(95%CI:1.727～3.990),OR突=8.254(95%CI:3.819～17.837)。
3、基因-环境因素之间交互作用研究结果显示:ERCC1-8092基因多态性与吸烟存在交互作用(OR=99.699,95%CI =5.239～297.133),未发现ERCC1-4533基因多态性与环境因素存在交互作用。
结论
ERCC1基因4533位点和8092位点多态可能与肝癌遗传易感有关。吸烟总量,喜食猪油,喜食腌制食品,食用霉变食物史,一级亲属肝癌史,乙肝肝炎史,家庭生活不和谐是肝癌的危险因素,有乙肝肝炎史为肝癌的第一危险因素。饮茶是肝癌的保护因素。ERCC1-8092基因多态性与吸烟存在交互作用,使得肝癌发生风险明显增加。
Objective
The study intended to investigate the association between genetic polymorphism of repair gene ERCC1 and susceptibility to hepatoma, and the gene-environmental interaction in etiology of hepatoma.
Materials & methods
Using 1:1 matched case-control study, we have identified 283 hepatoma patients with pathology diagnosis from big hospitals during the periods in Fuzhou city. A total of 283 controls without history of malignant tumor were selected during the same period and matched to each case by gender, age, nationality and inhabited areas. The constructed questionnaires were administered, and the geneotyping of ERCC1 was examined with PCR-RFLP analysis.Conditional logistic regression was used to analyze the role of environmental factors, gene, gene-environmental interaction in the progress of hepatoma, and to calculate odds ratios and 95% confidence intervals. All the calculations and statistics were performed with the computer program, SPSS Version 13.0.
Results
1.Multivariate conditional logistic regression analysis showed that tobacco smoking amount (OR=3.543,95%CI=1.605～7.819),eating lard (OR=4.499, 95%CI= 1.629～12.424),eating pickled food (OR=9.006,95%CI=3.047～26.622),eating moldy food(OR=6.356,95%CI=1.128～35.803),hepatoma history of first degree relative(OR=3.088,95%CI=1.114～8.562),hepatitis B (OR=19.069,95%CI=5.496～66.164),disharmony of family life(OR=2.000, 95%CI=1.346～2.970) were the risk factors of hepatoma cancer; while drinking tea (OR=0.229, 95%CI=0.068～0.766) was the protective factor of hepatoma.Hepatitis B was the greatest risk factor of hepatoma.
2. The distribution of ERCC1-4533 wild-type homozygote(G/G)、heterozygote(G/A)and mutant homozygote(A/A)in hepatoma cases and controls was significant difference(χ2=19.537, P<0.05), heterozygote and mutant homozygote had a increased risk of hepatoma (OR杂=1.675,95%CI:1.165～2.408;OR突=5.218,95%CI:1.949～13.956) compared to wild-type homozygote.
The distribution of ERCC1-8092 wild-type homozygote(C/C)、heterozygote(C/A)and mutant homozygote(A/A)in hepatoma cases and controls was significant difference(χ2=55.334 , P<0.05), heterozygote and mutant homozygote had a significant increased risk of hepatoma (OR杂=2.625,95%CI:1.727～3.990;OR突=8.254,95%CI:3.819～17.837) compared to wild-type homozygote.
3.The analysis of gene-environment interaction showed that tobacco smoking amount appeared interaction with genetic polymorphism of ERCC1-8092.No obvious interaction was observed between genetic polymorphism of ERCC1-4533 and the risk factors of hepatoma. Conclusion
The gene polymorphism of ERCC1-4533,ERCC1-8092 was possibly susceptible to hepatoma. Tobacco smoking amount, eating lard, eating pickled food, eating moldy food , hepatoma history of first degree relative, hepatitis B, disharmony of family life were the risk factors for hepatoma; while drinking tea was regarded as the protective factor to hepatoma.Hepatitis B was the greatest risk factor of hepatoma.There was interaction between tobacco smoking amount and genetic polymorphism of ERCC1-8092,that would aggravate the risk of suffering from hepatoma.
引文
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