Homocysteine-driven oxidative stress in pediatric lymphoma: a cross-sectional study of metabolic and genetic modulators

Hyperhomocysteinemia and oxidative stress are increasingly recognized in pediatric malignancies, but their interplay remains unclear. We evaluated homocysteine metabolism, vitamin cofactor status, and oxidative stress in 90 children with newly diagnosed lymphoma before chemotherapy. Plasma homocysteine, folate, vitamins B₁₂ and B₆, and oxidative stress markers (8-OHdG, nitrotyrosine, protein carbonyls, NO, iNOS) were measured, alongside MTHFR C677T genotyping. Hyperhomocysteinemia (>15 μmol/L) was present in 96% (n = 87), with low folate (median 2.6 ng/mL) and B₁₂ deficiency (B₁₂<200 pg/mL in 84%, n = 76). Homocysteine correlated inversely with folate and B₆, and positively with 8-OHdG (p < 0.05). MTHFR 677CT carriers had markedly elevated nitrotyrosine and higher 8-OHdG (p < 0.05), independent of homocysteine levels. In multivariate analysis, the T-allele predicted nitrotyrosine (p < 0.05), while homocysteine did not. These findings demonstrate profound disruption of one-carbon metabolism and oxidative stress in pediatric lymphoma at diagnosis, with genetic and micronutrient factors modulating the oxidative burden, emphasizing the value of early metabolic assessment.