On the other hand, the presence of an E2F binding site within the p18INK4C promoter (Blais et al., 2002) raised the possibility of a regulatory loop, where inactivation of p16INK4A in nascent cancer cells triggers a compensatory upregulation of p18INK4C via E2F, leading to genetic pressure for its concomitant or subsequent deletion. This evidence concerns the gene CDKN2A and cancer.