Association of MTHFR variant A1298C and TYMS polymorphisms with Retinoblastoma

Introduction: Retinoblastoma is the most common intraocular tumor of children under 6-years-old that arises of uncontrolled proliferation and growth in the retina.Folate and methionine metabolisms are involved in DNA synthesis and methylation, and polymorphisms in genes of folate metabolizing enzymes have been associated with some forms of cancer . MTHFR is one of the most important genes of this pathway and the A1298C polymorphism of this gene and thymidylate synthase gene have been found to reduced the MTHFR and TYMS enzyme activity and it lead to lower folate levels. Low levels of folate during retinogenesis may haveincreased uracil misincorporation, hypomethylation and, as a consequence, be more likely to develop postzygotic mutationsin RB1 . The aim of the current study is to evaluate association between MTHFR A1298C polymorphism and TYMS genewith retinoblastoma. Methods: A case- control study of 96 retinoblastoma cases and 204 cancer-free children controls was performed to investigate whether the polymorphism of the MTHFR (A1298C) and thymidylate synthase altered the risk forretinoblastoma in Iranian population. MTHFR A1298C was evaluated using ARMS-PCR and Also TYMS 2R>3R Was investigated by PCR. The results were analyzed using Chi square test and SPSS software. Results: MTHFR A1298C allelic frequencies of A and C alleles were 0.604 and 0.396 in cases and 0.581and 0.419 in controls, respectively (P=0.474). Also 2R and 3R allelic frequencies of TYMS gene were 0.396 and 0.604 in cases and 0.365 and 0.635 in controls, respectively (P=0.181). Conclusion:No associations were found between MTHFR A1298C polymorphism and TYMS gene with retinoblastoma in Iranian population. Further studies in larger cohorts are needed to be performed

Keywords:

Retinoblastoma , polymorphism , MTHFR , TYMS