Wang Li, Lin Dong-xin, Lu Xing-hua, Miao Xiao-ping, Li Hui
Department of Epidemiology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2006 Jan;27(1):50-4.
To determine whether genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G) were associated with the risks of pancreatic cancer.
A hospital-based, case-control study consisting of 101 incident pancreatic cancer cases and 337 controls 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 reasction-restriction fragment length polymorphism methods.
It was found that multivariate-adjusted odds ratio (ORs; 95% confidence interval) for MTHFR-677CT and 677TT compared with 677CC were 2.17 (1.26 - 3.85) and 3.53 (1.85 - 6.84) respectively, which was in a manner of allele-dose 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 gene-environment interaction was observed between C677T polymorphism and cigarette smoking or alcohol intake. Subjects with variant genotypes who smoked > 17 pack-years had highest risk for developing the cancer, with the OR of 5.58 (2.53 - 12.30). Similarly, the OR (3.27, 1.51 - 7.23) 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 A2756G polymorphism and risk of pancreatic cancer in the study.
These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.
确定亚甲基四氢叶酸还原酶（MTHFR C677T和A1298C）、甲硫氨酸合成酶（MS A2756G）的基因多态性是否与胰腺癌风险相关。
开展一项基于医院的病例对照研究，纳入101例新发胰腺癌病例和337例年龄、性别和种族相匹配的对照，以调查MTHFR和MS基因多态性与胰腺癌易感性之间的关联。采用聚合酶链反应-限制性片段长度多态性方法分析MTHFR C677T、A1298C和MS A2756G的基因型。
发现MTHFR - 677CT和677TT与677CC相比，多因素调整后的比值比（OR；95%置信区间）分别为2.17（1.26 - 3.85）和3.53（1.85 - 6.84），呈等位基因剂量关系。然而，未观察到单独的A1298C基因型与癌症风险之间存在显著关联，似乎该多态性与C677T多态性存在联合效应。观察到C677T多态性与吸烟或饮酒之间存在显著的基因-环境相互作用。吸烟超过17包年的变异基因型受试者患癌风险最高，OR为5.58（2.53 - 12.30）。同样，饮酒者变异基因型受试者的OR（3.27，1.51 - 7.23）显著高于变异基因型或饮酒者。本研究未发现MS A2756G多态性与胰腺癌风险之间存在关联。
这些发现支持了MTHFR C677T基因多态性可能导致胰腺癌发生风险增加的假说。
