CDKN2A and esophageal squamous cell carcinoma: In terms of the functional effect of the variant in CDKN2A (p16INK4A, D74A) on protein function, it is likely that this variant is significant, as mutation of aspartic acid 74, to asparagine has been identified in bladder carcinoma [31] and esophageal squamous cell carcinoma [32].