Kim Jin Kyeoung, Kim Sehyun, Han Jin Hee, Kim Hyo Jin, Chong So Young, Hong Seong Pyo, Hwang Seong Gyu, Ahn Jung Yong, Cha Kwang Yul, Oh Doyeun, Kim Nam Keun
Institute for Clinical Research, 2Graduate School of Life Science and Biotechnology, College of Medicine, Pochon CHA University, Seongnam 463-712, South Korea.
Anticancer Res. 2005 May-Jun;25(3B):2249-52.
Methylentetrahydrofolate reductase plays a central role in converting folate to methyl donor for DNA methylation. Genetic variations in folate metabolism are believed to contribute to the risk of acute lymphoblastic leukemia, colon, esophageal and stomach cancer, as well as cardiovascular and cerebrovascular diseases. MTHFR C677T and A1298C polymorphisms are known to be risk factors for gastric cancer in the Chinese population. Therefore, we hypothesized that the MTHFR polymorphisms are associated with the risk of stomach cancer in Korean subjects.
We conducted a Korean population-based case-control study to examine the relationship between genetic polymorphisms in MTHFR and risk of stomach cancer. The study subjects were 133 patients with stomach cancer and 445 population controls, matched according to sex and age. Genomic DNA was extracted from blood samples of the controls and from surgically resected "normal" tissues adjacent to the tumor of stomach cancer patients. MTHFR genotypes at the C677T and A1298C sites were analyzed by PCR-based RFLP methods.
We found no evidence for an association between the MTHFR C677T and A1298C polymorphisms and stomach cancer in any of the subjects. The adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 0.924 (0.581-1.469) for 677CT versus 677CC wild-type and 1.147 (0.850-1.549) for 677TT versus 677CC, and for MTHFR A1298C, they were 1.114 (0.695-1.783) for 1298AC versus 1298AA wild-type and 0.834 (0.284-2.450) for 1298CC versus 1298AA.
These results suggest that the MTHFR C677T and A1298C polymorphisms by themselves do not play an important role in the etiology of stomach cancer in the Korean population.
亚甲基四氢叶酸还原酶在将叶酸转化为DNA甲基化的甲基供体过程中发挥核心作用。叶酸代谢的基因变异被认为与急性淋巴细胞白血病、结肠癌、食管癌和胃癌以及心血管和脑血管疾病的风险有关。已知MTHFR C677T和A1298C多态性是中国人群胃癌的危险因素。因此，我们推测MTHFR多态性与韩国人患胃癌的风险有关。
我们进行了一项基于韩国人群的病例对照研究，以检验MTHFR基因多态性与胃癌风险之间的关系。研究对象为133例胃癌患者和445名根据性别和年龄匹配的人群对照。从对照的血液样本以及胃癌患者肿瘤旁手术切除的“正常”组织中提取基因组DNA。通过基于PCR的RFLP方法分析C677T和A1298C位点的MTHFR基因型。
我们在任何研究对象中均未发现MTHFR C677T和A1298C多态性与胃癌之间存在关联的证据。MTHFR C677T的校正比值比和95%置信区间，677CT与677CC野生型相比为0.924（0.581 - 1.469），677TT与677CC相比为1.147（0.850 - 1.549）；对于MTHFR A1298C，1298AC与1298AA野生型相比为1.114（0.695 - 1.783），1298CC与1298AA相比为0.834（0.284 - 2.450）。
这些结果表明，MTHFR C677T和A1298C多态性本身在韩国人群胃癌的病因学中并不起重要作用。
