MTHFR single nucleotide polymorphism associated with working memory in pediatric medulloblastoma survivors

Abstract

ABSTRACT Background: Associations have been found between single nucleotide polymorphisms (SNPs) in the MTHFR gene and cognitive outcomes in cancer survivors. Prior research has demonstrated that the presence of MTHFR SNPs (rs1801131 and rs1801133) in survivors of acute lymphoblastic leukemia (ALL) corresponds to impairments in attention and executive functioning. The current study examines the associations between rs1801131 and/or rs1801133 SNPs and cognitive performance in long-term survivors of medulloblastoma. Procedure: Eighteen pediatric medulloblastoma survivors, on average 12.42 years post-diagnosis, completed the Digit Span Forward, Digit Span Backward, California Verbal Learning Test Trial 1, and Auditory Consonant Trigrams tests. MTHFR SNPs were detected using whole genome sequencing data and custom scripts within R software. Results: Survivors with a rs1801131 SNP performed significantly worse on Digit Span Backward than survivors without this SNP exhibiting a large effect (p = 0.049; d = 0.95). Survivors with a rs1801131 SNP performed worse on Digit Span Forward (d = 0.478) and the CVLT Trial 1 (d = 0.417) with medium effect sizes. In contrast to rs1801131, relationships were not identified between a rs1801133 SNP and these performance measures. Conclusions: Our findings demonstrate the potential links between MTHFR SNPs and cognitive outcomes following treatment in brain tumor survivors. The current findings establish a novel relationship between rs1801131 and working memory in medulloblastoma. Increases in homocysteine levels and oxidative damage from radiation may lead to adverse long-term outcomes. This establishes the need to look beyond leukemia and methotrexate treatment to consider the risk of MTHFR SNPs for medulloblastoma survivors.