Genetic and epigenetic variants in the MTHFR gene are not associated with non-Hodgkin lymphoma

The methylenetetrahydrofolate reductase (MTHFR) gene codes for the MTHFR enzyme which plays a key role in the pathway of folate andmethioninemetabolism. Polymorphisms of genes in this pathway affect its regulation and have been linked to lymphoma. In this studywe examinedwhether we could detect an association between two common non-synonymous MTHFR polymorphisms, 677C > T (rs1801133) and 1298A > C (rs1801131), and susceptibility to non-Hodgkin lymphoma (NHL) in an Australian case-control cohort. We found no significant differences between genotype or allele frequencies for either polymorphisms between lymphoma cases and controls. We also explored whether epigeneticmodification of MTHFR, specifically DNA methylation of a CpG island in the MTHFR promoter region, is associatedwith NHL using blood samples frompatients. No difference in methylation levelswas detected between the case and control samples suggesting that although hypermethylation of MTHFR has been reported in tumour tissues, particularly in the diffuse large B-cell lymphoma subtype of NHL, methylation of thisMTHFR promoter CpG island is not a suitable epigenetic biomarker for NHL diagnosis or prognosis in peripheral blood samples. Further studies into epigenetic variants could focus on genes that are robustly associated with NHL susceptibility. (C) 2015 The Authors. Published by Elsevier B.V.