亚甲基四氢叶酸还原酶基因多态性、饮酒与结直肠癌关系的病例对照研究

蒋沁婷; 陈坤; 俞维萍; 李凌云; 朱益民; 周海光; 马新源; 姚开颜; 缪小平

Abstract

蒋沁婷,陈坤,俞维萍,李凌云,朱益民,周海光,马新源,姚开颜,缪小平.亚甲基四氢叶酸还原酶基因多态性、饮酒与结直肠癌关系的病例对照研究[J].Chinese journal of Epidemiology,2004,25(7):612-616

亚甲基四氢叶酸还原酶基因多态性、饮酒与结直肠癌关系的病例对照研究

A case-control study on the polymorphisms of methylenetetrahydrofolate reductases.drinking interaction and susceptibility in colorectal cancer

Received:May 15, 2003

DOI：

KeyWord: 亚甲基四氢叶酸还原酶结直肠肿瘤基因多态性易感性

English Key Word: Methylenetetrahydrof0late reductases Colorectal neoplasms Genetic polymorphisms Tumor susceptibility

FundProject:国家自然科学基金(30170828)

Author Name	Affiliation
JIANG Qin-ting	Department of Epidemiology and Statistical, School of Medicine, Zhejiang University Hangzhou 310031 China
CHEN Kun	Department of Epidemiology and Statistical, School of Medicine, Zhejiang University Hangzhou 310031 China
MA Xin-yuan	Department of Epidemiology and Statistical, School of Medicine, Zhejiang University Hangzhou 310031 China
MIAO Xiao-ping	Department of Epidemiology and Statistical, School of Medicine, Zhejiang University Hangzhou 310031 China
YAO Kai-yan	Department of Epidemiology and Statistical, School of Medicine, Zhejiang University Hangzhou 310031 China
YU Wei-ping	Department of Epidemiology and Statistical, School of Medicine, Zhejiang University Hangzhou 310031 China
LI Ling-yun	浙江省嘉善县肿瘤防制所
ZHU Yi-min	浙江省嘉善县肿瘤防制所
ZHOU Hai-guang	中国协和医科大学肿瘤研究所病因及癌变研究室

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Abstract:

目的研究亚甲基四氢叶酸还原酶(MTHFR)基因多态与结直肠癌(包括结肠癌、直肠癌)易感性的关系.方法应用聚合酶链反应(PCR)和限制性片段长度多态性方法(RFLP)，检测了126例结直肠癌患者和343名正常对照的MTHFR C677T和A1298C两个位点基因多态，并比较不同基因型单独、联合时与结直肠癌风险的关系，以及两个多态位点与饮酒的联合作用.结果MTHFR677T和1298C突变基因在对照组中的频率分别为39.7%和17.1%.1298C突变基因携带者与野生型相比，患结直肠癌的风险均降低;在携带677C和1298C等位基因组合个体中，结直肠癌的风险略有降低(0R=0.718，95%CI:0.367～1.407)，同时含677T和1298A等位基因者，结直肠癌的风险降低1倍;同时含有677T和1298C等位基因者，结直肠癌的风险降低4倍，直肠癌的风险降低7倍(0R=0.304，95%CI:0.108～0.852).在过去饮酒者中，1298A等位基因携带者结直肠癌风险性增加2倍(0R=3.307，95%CI:0.521～17.698).结论 MTHFR C667T和A1298C位点多态性在结直肠癌发生过程中起着-定作用，携带MTHFR 1298AC基因多态型者过去饮酒是结直肠癌的危险因素.

English Abstract:

Objective to investigate the relationship between methylenetetrahydrofolate reductases(MTHFR)polymorphisms and colorectal cancer susceptibility.Methods A case-control study of 126 patients and 343 healthy controls was conducted to investigate the roles of MTHFR C677T and A1298C polymorphisms in colorectal cancer development.Genotypes of C677T and A1298C polymorphisms were analyzed by polymerase chain resction-restriction fragment length polymorphism (PCR-RFLP)methods.Results The frequencies of MTHFR 677T and 1298C allele were 39.7% and 17.1%.respectively.After adjustment for age and sex,the MTHFR 1298C alleles seemed to have reduced association on the risk of colorectal cancer comparing to wild types.Among those with 677T and 1298A alleles.a decreased risk of colorectal cancer was observed:a 4-fold decrease in colorectal cancer risk(0R=0.552.95%CI:0.265-1150) in those with 677T and 1298C alleles.Men who were ex-drinkers and with MTHFR 1298C allele had a 2-fold increase in risk of colorectal cancer(0R=3.307,95%CI:0.521-17.698)while no increased risk was seen among those current-drinkers. Conclusions This study suggested that certain MTHFR C677T and A1298C might be associated with the risk of colorectal cancer development.The interaction between MTHFR 1298AC polymorphisms and ex-drinking might also serve as a risk factor of colorectal Cancer.

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