However, systemically reducing p16Ink4a or p53-p21Cip1/Waf1 expression is likely to increase cancer risk since p53, p21Cip1/Waf1, and p16Ink4a global KO mice have a high prevalence of cancer and hence a shorter lifespan than control mice (250-253). The gene discussed is CDKN1A; the disease is cancer.