Clinical Significance of MTHFR C677T and A1298C Polymorphisms in Adult Patients with ALL and NHL

<b>Background/Objectives:</b> Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms may influence folate metabolism and DNA synthesis, potentially affecting disease characteristics and clinical outcomes in hematologic malignancies. This study investigated the associations of MTHFR C677T and A1298C polymorphisms with clinical features and survival outcomes in adult patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). <b>Methods:</b> A total of 92 adult patients with ALL or NHL treated with standard chemotherapy were retrospectively analyzed. MTHFR C677T and A1298C genotypes were determined using real-time polymerase chain reaction. Associations between genotypes and baseline clinical features, treatment response, toxicity, overall survival (OS), and progression-free survival (PFS) were examined. <b>Results:</b> The C677T heterozygous genotype was significantly associated with the presence of B symptoms (<i>p</i> = 0.027). No significant differences were observed across genotypes with respect to other baseline clinical features, treatment response, or treatment-related toxicity. In the overall cohort (ALL + NHL), OS and PFS did not differ significantly by C677T or A1298C genotypes. However, in the NHL cohort, carriers of the C677T variant demonstrated significantly shorter PFS (<i>p</i> = 0.048) and a non-significant trend toward lower OS. This association was also observed in the DLBCL subgroup for PFS (<i>p</i> = 0.043), with a similar non-significant trend observed for OS. <b>Conclusions:</b> Although MTHFR genotyping appears to have limited value for broad clinical stratification, the observed association between the C677T polymorphism and PFS in NHL-particularly in the DLBCL subgroup-suggests a potential subtype-specific relevance that warrants further validation in larger, disease-specific cohorts.