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

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MTHFR C677T、A1298C及MS A2756G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-677 CT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MTHFR 1298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MS A2756G多态与胰腺癌的发生之间存在统计学的显著关联.结论 MTHFR C677T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.

Objective To 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 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-restfiction fragment length polymorphism methods. Results 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. Conclusion These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.