Furthermore, it is well known that the risk for developing lung cancer in smokers is 8 to 13 times higher than that in nonsmokers, while the risk of p16INK4α hypermethylation in lung cancer patients with smoking habits was only 2.2 times increased than that in nonsmoker patients, we speculate that many other aberrant epigenetic modifications, together with the genetic damage are involved in lung cancer development, which needs to be addressed in further investigation. This evidence concerns the gene CDKN2A and lung cancer.