As compared with healthy individuals, DNA methylation of the tumor suppressor genes APC and RASSF1A was altered in circulating cell-free DNA of patients with breast or gastric cancer.39–42 DNA methylation of cell cycle-related genes such as P16INK4, 14-3-3δ, GSTP1, p15, p16, RAR-β, and SEPT9 was reported in bladder, lung, prostate, and colorectal cancer and in head and neck squamous cell carcinoma.43–48 However, almost all these studies failed to adjust for confounding factors, including well-known cancer risk factors. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.