CDKN2A and lung carcinoma: Furthermore, reduced expression of p16INK4a and aberrantly up-regulated methylation of p16INK4a promoter were also discovered in human workers with lung cancer and long-term (≥15 years) exposure to Cr(VI), suggesting that the hypermethylation of p16INK4a is involved in the Cr(VI) carcinogenesis [51].