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.

摘要

背景：已发现MTHFR基因中的单核苷酸多态性 (SNP) 与癌症幸存者的认知结果之间存在关联。先前的研究表明，急性淋巴细胞白血病 (ALL) 幸存者中MTHFR SNP（rs1801131 和 rs1801133）的存在对应于注意力和执行功能的损害。目前的研究检查了 rs1801131 和/或 rs1801133 SNP 与髓母细胞瘤长期幸存者的认知能力之间的关联。程序： 18 名小儿髓母细胞瘤幸存者，平均在诊断后 12.42 年完成了数字跨度向前、数字跨度向后、加利福尼亚语言学习测试试验 1 和听觉辅音三元组测试。使用全基因组测序数据和 R 软件中的自定义脚本检测MTHFR SNP。结果：具有 rs1801131 SNP 的幸存者在向后数字跨度上的表现明显低于没有此 SNP 的幸存者表现出大的影响（p = 0.049；d = 0.95）。具有 rs1801131 SNP 的幸存者在数字跨度前向 ( d = 0.478) 和 CVLT 试验 1 ( d = 0.417) 中表现更差，效果中等。与 rs1801131 相比，未确定 rs1801133 SNP 与这些性能测量之间的关系。结论：我们的研究结果证明了MTHFR之间的潜在联系脑肿瘤幸存者治疗后的 SNP 和认知结果。目前的研究结果在髓母细胞瘤中建立了 rs1801131 与工作记忆之间的新关系。同型半胱氨酸水平升高和辐射造成的氧化损伤可能导致不良的长期结果。这确立了超越白血病和甲氨蝶呤治疗的需要，以考虑髓母细胞瘤幸存者的MTHFR SNP 风险。