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Background  The study aimed to explore the associations between the interactions of serum vitamin B 2  or B 12  levels, aberrant DNA methylation of p16 or p53 and MTHFR C677T polymorphism and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal precancerous lesion (EPL).    Methods  200 ESCC cases, 200 EPL cases and 200 normal controls were matched by age (± 2 years) and gender. Serum vitamin B 2  and B 12  levels, MTHFR C677T genetic polymorphisms and the methylation status of genes were assessed. Chi square test, one-way analysis of variance and binary logistic regression were performed.    Results  The lowest quartile of both serum vitamin B 2  and B 12  with TT genotype showed significant increased EPL risk (OR = 4.91, 95% CI 1.31–18.35; OR = 6.88, 95% CI 1.10–42.80). The highest quartile of both serum vitamin B 2  and B 12  with CC genotype showed significant decreased ESCC risk (OR = 0.16, 95% CI 0.04–0.60; OR = 0.10, 95% CI 0.02–0.46). The ORs of p16 methylation for genotype CT and TT were 1.98 (95% CI 1.01–3.89) and 17.79 (95% CI 2.26–140.22) in EPL, 4.86 (95% CI 2.48–9.50) and 20.40 (95% CI 2.53–164.81) in ESCC, respectively. Similarly, p53 methylation with genotype TT was associated with increased EPL and ESCC risks (OR = 13.28, 95% CI 1.67–105.70; OR = 15.24, 95% CI 1.90–122.62).    Conclusions  The MTHFR C677T genotype and serum vitamin B 2  or B 12  levels may interact in ways which associated with the EPL and ESCC risks. The gene–gene interaction suggested that aberrant DNA methyaltion of either p16 or p53 combined with T alleles of MTHFR was associated with increased risks of both EPL and ESCC.

cancer cell international

MTHFR C677T genetic polymorphism in combination with serum vitamin B2, B12 and aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and esophageal precancerous lesions: a case–control study