APP and cancer: This article reviews the pathophysiology and clinical conditions of AT as a serine protease inhibitor with a case history of inherited AT deficiency: Arg393His in AT-Hanoi [16], and discusses the conditions of acquired risk factors such as cancer or genetic disorders via epigenetic modifications in gene-gene (epistasis) and/or gene-environment interactions such as in Lesch-Nyhan disease (LND), in which the β-amyloid precursor protein (APP) that may interact to predispose a patient to thrombosis and cancer as well, and finally, concludes with some future perspectives.