Contribution of MTHFR C677T and A1298C Variants to Retinoblastoma Risk in Mexican Children

Background: Retinoblastoma (RB) is the most common malignant intraocular tumor in childhood. Although germline and somatic alterations in RB1 contribute to RB development, additional genetic factors may influence susceptibility. Methylenetetrahydrofolate reductase (MTHFR) participates in folate metabolism and DNA synthesis and repair. This study evaluated the association of MTHFR C677T and A1298C polymorphisms with RB susceptibility in Mexican children. Methods: A case–control study included 58 Mexican children with clinically diagnosed RB and 301 healthy controls matched for sex and ethnicity. Genomic DNA was extracted from peripheral blood, and MTHFR C677T (rs1801133) and A1298C (rs1801131) were genotyped using TaqMan allelic discrimination assays. Allele and genotype frequencies were compared using chi-square and Fisher’s exact tests. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A recessive genetic model was applied to both polymorphisms. Results: The MTHFR 677TT genotype was associated with significantly reduced odds of RB under the recessive genetic model (TT vs. CC + CT), using Firth’s penalized logistic regression (OR = 0.066; 95% CI: 0.007–0.250, p < 0.001). The T allele was also less frequent among cases, supporting a potential protective association. No significant association was observed between MTHFR A1298C and RB susceptibility (p = 0.262). Conclusions: The MTHFR C677T polymorphism was associated with RB susceptibility in this Mexican cohort, with the TT genotype showing a potential protective association. No significant association was identified for A1298C. Further studies are warranted to investigate the role of MTHFR variation and folate-dependent DNA metabolism in RB susceptibility.