Research Center for Gastroenterology and Liver Diseases, Taleghani Hospital, Shaheed Beheshti Medical University, Tehran, Iran.
Oncol Res. 2009;18(2-3):57-63. doi: 10.3727/096504009789954636.
The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) is linked to DNA methylation, synthesis, and repair. C677T is one of the most important polymorphisms in the MTHFR gene. The single nucleotide polymorphism C677T has been found to be associated with decreased enzyme activity and plasma folate, and thus may play a crucial role in the etiology of colorectal cancer. This decrease was observable in people with either high or low folate status. We aimed to test the hypothesis that the C677T genotype is involved in colorectal cancer. Using pyrosequencing, we analyzed the MTHFR genotypes in 234 colorectal cancer patients and 257 matched controls. We examined the polymorphisms in MTHFR and folate intake in relation to risk of colon cancer in an Iranian population-based case-control study. Our finding revealed that the CC, CT, and TT genotypes of MTHFR among the colorectal cancer patients were 50%, 29.1%, and 20.9%, respectively. On the other hand, we could find 29.5% of 677CC, 46% of 677CT and 24.5% of 677TT in the controls. A decreased risk of colon cancer for participants with wild-type genotype was observed. Interestingly, this association was stronger at higher levels of folate intake. Our study corroborates previous findings of an inverse association of the MTHFR 677TT genotype with colorectal cancer, in particular at high levels of folate.
酶 5,10-亚甲基四氢叶酸还原酶 (MTHFR) 与 DNA 甲基化、合成和修复有关。C677T 是 MTHFR 基因中最重要的多态性之一。单核苷酸多态性 C677T 与酶活性和血浆叶酸降低有关，因此可能在结直肠癌的病因中起关键作用。这种降低在叶酸水平高或低的人群中均可观察到。我们旨在检验 C677T 基因型是否与结直肠癌有关的假设。使用焦磷酸测序，我们分析了 234 例结直肠癌患者和 257 例匹配对照的 MTHFR 基因型。我们在伊朗基于人群的病例对照研究中研究了 MTHFR 中的多态性和叶酸摄入与结肠癌风险的关系。我们的研究结果表明，结直肠癌患者的 MTHFR CC、CT 和 TT 基因型分别为 50%、29.1%和 20.9%。另一方面，我们在对照组中发现了 677CC 的 29.5%、677CT 的 46%和 677TT 的 24.5%。具有野生型基因型的参与者患结肠癌的风险降低。有趣的是，这种关联在叶酸摄入量较高时更强。我们的研究证实了先前关于 MTHFR 677TT 基因型与结直肠癌呈负相关的发现，尤其是在叶酸水平较高时。
