Wang Li, Miao Xiaoping, Tan Wen, Lu Xinghua, Zhao Ping, Zhao Xiaohang, Shan Yi, Li Hui, Lin Dongxin
Department of Epidemiology, Institute of Basic Medical Sciences, Cancer Institute & Hospital, Beijing, China.
Clin Gastroenterol Hepatol. 2005 Aug;3(8):743-51. doi: 10.1016/s1542-3565(05)00156-4.
BACKGROUND & AIMS: Human pancreatic cancer might be associated with folate deficiency and impaired metabolism. We tested this hypothesis by examining the contribution of functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) to risk of cancer.
DNA from 163 pancreatic cancer patients and 337 control subjects was genotyped for MTHFR (677C > T and 1298A > C) and TS (5'-untranslated region tandem repeat and G/C). Association with risk of pancreatic cancer was estimated by logistic regression. All statistical tests were two-sided.
We observed an increased risk of pancreatic cancer associated with the MTHFR 677CT (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.61-4.29; P = .0005) or 677TT (OR, 5.12; 95% CI, 2.94-9.10; P < .0001) genotype compared with the MTHFR CC genotype. An increased risk of pancreatic cancer was also associated with the TS 3Rc/3Rc genotype (OR, 2.19, 95% CI, 1.13-4.31; P = .022) compared with the TS 3Rg/3Rg genotype. Joint effect between MTHFR C677T polymorphism and smoking or drinking increased risk of pancreatic cancer in a super-multiplicative manner. The ORs for smoking, the polymorphism, and both factors combined were 0.70 (95% CI, 0.30-1.63), 2.17 (95% CI, 1.17-4.21), and 3.10 (95% CI, 1.54-6.51), respectively. This joint effect was much stronger in heavy smokers (OR, 6.69; 95% CI, 3.39-13.63; P < .0001). The ORs for drinking, the polymorphism, and both factors combined were 0.98 (95% CI, 0.40-2.30), 2.81 (95% CI, 1.65-4.98), and 4.39 (95% CI, 2.25-8.78), respectively.
The MTHFR and TS polymorphisms are genetic determinants for developing pancreatic cancer.
人类胰腺癌可能与叶酸缺乏及代谢受损有关。我们通过研究亚甲基四氢叶酸还原酶（MTHFR）和胸苷酸合成酶（TS）的功能多态性对癌症风险的影响来验证这一假设。
对163例胰腺癌患者和337例对照者的DNA进行MTHFR（677C>T和1298A>C）及TS（5'-非翻译区串联重复序列和G/C）基因分型。通过逻辑回归评估与胰腺癌风险的相关性。所有统计检验均为双侧检验。
与MTHFR CC基因型相比，我们观察到携带MTHFR 677CT（优势比[OR]，2.60；95%置信区间[CI]，1.61 - 4.29；P = 0.0005）或677TT（OR，5.12；95% CI，2.94 - 9.10；P < 0.0001）基因型的患者患胰腺癌的风险增加。与TS 3Rg/3Rg基因型相比，TS 3Rc/3Rc基因型也与胰腺癌风险增加相关（OR，2.19，95% CI，1.13 - 4.31；P = 0.022）。MTHFR C677T多态性与吸烟或饮酒之间的联合效应以超相乘方式增加了胰腺癌风险。吸烟、该多态性以及两者共同作用的OR分别为0.70（95% CI，0.30 - 1.63）、2.17（95% CI，1.17 - 4.21）和3.10（95% CI，1.54 - 6.51）。这种联合效应在重度吸烟者中更强（OR，6.69；95% CI，3.39 - 13.63；P < 0.0001）。饮酒、该多态性以及两者共同作用的OR分别为0.98（95% CI，0.40 - 2.30）、2.81（95% CI，1.65 - 4.98）和4.39（95% CI，2.25 - 8.78）。
MTHFR和TS多态性是胰腺癌发生的遗传决定因素。
