Stem Cell Laboratory, Center for Bone Marrow Transplants, Brazilian National Cancer Institute-INCA, Rio de Janeiro 20230-240, Brazil.
Stricto Sensu Graduate Program in Oncology, INCA, Rio de Janeiro 20230-240, Brazil.
Genes (Basel). 2021 Apr 17;12(4):587. doi: 10.3390/genes12040587.
Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning polymorphisms.
叶酸(维生素 B9)存在于一些水溶性食物中或作为合成叶酸的形式,参与许多重要的生化过程。膳食叶酸转化为四氢叶酸,是大多数甲基化反应的重要甲基供体,包括 DNA 甲基化。5,10-亚甲基四氢叶酸还原酶(MTHFR)是叶酸代谢途径中的关键酶,将 5,10-亚甲基四氢叶酸转化为 5-甲基四氢叶酸,为同型半胱氨酸向蛋氨酸的再甲基化提供甲基供体。 多态性导致酶活性降低和 DNA 甲基化和合成水平改变。 多态性与多种病理的风险增加有关,包括癌症。乳腺癌、神经胶质瘤和胃癌是高度异质性和侵袭性疾病,与高死亡率相关。 多态性对这些肿瘤的影响在文献中仍存在争议。这篇综述讨论了 C677T 和 A1298C 多态性与乳腺癌、神经胶质瘤和胃癌风险增加之间的关系。此外,我们强调了人群为基础的研究的种族和饮食方面以及高度异质性肿瘤的组织学分层的相关性。最后,这篇综述讨论了这些方面作为导致有关 多态性的文献存在争议的潜在因素。