TP53 and esophageal squamous cell carcinoma: Our study suggested that: firstly, healthy controls were more likely to have higher levels of vitamin B2 and B12 than ESCC cases; secondly, variant genotype TT and the T allele were associated with significantly increased risk of EPL; thirdly, the MTHFR C677T genotype may modify association between serum vitamin B2 or B12 levels and the risks of EPL and ESCC; fourthly, gene–gene interaction was observed as there were strong association between the interaction of p16 and p53 methylations and MTHFR C677T polymorphism and the risks of EPL and ESCC.