叶酸代谢相关基因MTHFR、MS基因多态与胰腺癌风险关联

王丽; 林东昕; 陆星华; 缪小平; 李辉

Abstract

王丽,林东昕,陆星华,缪小平,李辉.叶酸代谢相关基因MTHFR、MS基因多态与胰腺癌风险关联[J].Chinese journal of Epidemiology,2006,27(1):50-54

叶酸代谢相关基因MTHFR、MS基因多态与胰腺癌风险关联

Study on the relations between genetic polymorphisms in methylenetetrahydrofolate reductase,methionine synthase and the risk of pancreatic cancer

Received:April 05, 2005

DOI：

KeyWord: 胰腺癌亚甲基四氢叶酸还原酶甲硫氨酸合成酶遗传易感性

English Key Word: Pancreatic cancer Methylenetetrahydrofolate reductase Methionine synthase Genetic susceptibility

FundProject:卫生部临床重点学科资助项目(20010102)

Author Name	Affiliation
Wang Li	Department of Epidemiology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
Lin Dongxin	中国医学科学院肿瘤研究所病因与癌变研究室
Lu Xinghua	北京协和医院消化内科
Miao Xiaoping	中国医学科学院肿瘤研究所病因与癌变研究室
Li Hui	Department of Epidemiology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China

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Abstract:

目的探讨亚甲基四氢叶酸还原酶(MTHFR)及甲硫氨酸合成酶(MS)基因多态与胰腺癌风险的关系。方法采用以医院为基础的病例对照研究(胰腺癌新发病例101例,对照337人)方法,进行MTHFRC677T、A1298C及MSA2756G基因多态与胰腺癌风险关联分析,采用PCR-RFLP方法进行两候选基因分型。结果携带MTHFR-677CT及TT基因型者发生胰腺癌风险是CC基因型个体的2.17(95%CI:1.26~3.85)及3.53(95%CI:1.85~6.84)倍,呈明显的等位基因-效应关系;未观察到MTHFR1298多态单独对胰腺癌发生的影响,但发现它与C677T有联合作用。MTHFR677CT与TT基因型与吸烟、饮酒有明显的正向交互,产生交互作用的ORint值分别为1.78(P=0.0010)和2.10(P=0.0051)。未发现MSA2756G多态与胰腺癌的发生之间存在统计学的显著关联。结论MTHFRC677T多态与胰腺癌发生风险显著关联,且与吸烟、饮酒存在正向交互作用。

English Abstract:

ObjectiveTo determine whether genetic polymorphisms in methylenetetrahydrofolate reductase(MTHFR C677T and A1298C),methionine synthase (MS A2756G) were associated with the risks of pancreatic cancer. Methods　A hospital2based,case2control study consisting of 101 incident pancreatic cancer cases and 337controls matched on age, sex and race was conducted to investigate the association between polymorphism in MTHFR and MS,and susceptibility to pancreatic cancer. Genotypes of MTHFR C677T,A1298C and MS A2756G were analyzed by polymerase chain reasction2restriction fragment length polymorphism methods.Results　It wasfound that multivariate2adjusted odds ratio ( ORs ; 95 % confidence interval ) for MTHFR2677CT and 677TT compared with 677CC were 2. 17 (1. 2623. 85) and 3. 53 (1. 8526. 84) respectively,which was in a manner ofallele2dose relationship. However,no significant association between the A1298C genotype alone and the risk of cancer was observed which seemed that this polymorphism had a combined effect with the C677T polymorphism. A significant gene2environment interaction was observed between C677T polymorphism and cigarette smoking oralcohol intake. Subjects with variant genotypes who smoked > 17 pack2years had highest risk for developing the cancer,with the OR of 5. 58 (2. 53212. 30). Similarly, the OR (3. 27, 1. 5127. 23) for subjects with variant genotypes of alcohol drinker was significantly higher than that for subjects either having the variant genotype or being drinkers. No association was found between MS A2756Gpolymorphism and risk of pancreatic cancer in the study. Conclusion　These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.

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