MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

• Published in: Genes 2021-04, Vol.12 (4), p.587
• Main Authors: Petrone, Igor, Bernardo, Paula Sabbo, Dos Santos, Everton Cruz, Abdelhay, Eliana
• Format: Article
• Language: English
• Subjects: Acids; Brain Neoplasms - ethnology; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Breast cancer; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Carbon; Cell division; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA Methylation; Enzymatic activity; Enzymes; Esophageal cancer; Female; Folic acid; Folic Acid - metabolism; Gastric cancer; Gene expression; Genetic Predisposition to Disease; Glioma - ethnology; Glioma - genetics; Glioma - metabolism; Homocysteine; Humans; Male; Metabolism; Methionine; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Mortality; Plasma; Polymorphism; Polymorphism, Single Nucleotide; Population studies; Proteins; Review; Reviews; Stomach Neoplasms - ethnology; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Tetrahydrofolic acid; Tumors; Vitamin B
• ISSN: 2073-4425; 2073-4425
• 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.