Contribution of Methylenetetrahydrofolate Reductase Genotypes to Brain Tumor Risk Determination in Taiwan

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism, playing a critical role in DNA methylation and nucleotide synthesis. Variants of the MTHFR gene have been associated with varying susceptibility to brain tumors, particularly gliomas. This study aimed to investigate the role of MTHFR genotypes in determining brain tumor risk in Taiwan.

In this hospital-based case-control study, we assessed the contribution of MTHFR C677T (rs1801133) and A1298C (rs1801131) genotypes to brain tumor risk. A total of 52 patients with brain tumor and 520 age- and sex-matched non-cancer healthy controls were included. Genotyping of MTHFR rs1801133 and rs1801131 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Our findings revealed a significant difference in the genotypic distribution of MTHFR rs1801131 between brain tumor cases and non-cancer controls (p for trend=0.0099). Specifically, individuals with the MTHFR rs1801131 homozygous CC genotype demonstrated a 3.69-fold increased risk of brain tumors [95% confidence interval (95%CI)=1.52-9.00, p=0.0062]. In contrast, the AC genotype did not show a statistically significantly increased risk [odds ratio (OR)=1.54, 95%CI=0.83-2.85, p=0.2278]. Allelic frequency analysis revealed that the C allele of MTHFR rs1801131 was associated with an elevated risk of brain tumors (OR=1.83, 95%CI=1.20-2.80, p=0.0071). No significant association was found for MTHFR rs1801133. Stratified analysis showed that the MTHFR rs1801131 CC genotype particularly increased the risk in individuals older than 60 years (OR=4.68, 95%CI=1.42-15.42, p=0.0202) and in females (OR=3.79, 95%CI=1.22-11.77, p=0.0410).

The CC genotype of MTHFR rs1801131 may serve as a valuable marker for brain tumor susceptibility. Stratifying patients with brain tumors based on their MTHFR genotypes could help identify individuals at high risk, enabling more frequent monitoring and preventive measures to reduce the occurrence of brain tumors in Taiwan.