Translational Genetics in Hereditary Cancers for Personalized Medicine Practice

Abstract

Elucidation of the molecular and cellular basis of disease has ushered in the era of personalized medicine. Current data indicate that 5–10% of cancers are hereditary, that is, caused by germline mutations in cancer predisposition genes. Examples include hereditary breast and ovarian cancers, von Hippel-Lindau syndrome, Cowden syndrome, and Lynch syndrome. The discoveries of causative genetic mutations have been possible due to the identification of families with a preponderance of cancers. After identifying patients with hereditary cancers through accurate family history, the next step is to identify the causative mutation(s) in these high-risk patients and individuals. Such detection can inform treatment; for instance, BRCA1/2 mutation carriers have now the option of intervention with Poly-ADP Ribose Polymerase (PARP) inhibitors such as olaparib and niraparib. It is important to emphasize that the study of hereditary forms of cancers has led to better treatment options not only for these cancers but also for the nonhereditary forms, which are more common. As next-generation sequencing becomes more affordable, it is likely that more causative mutations will be identified. This information can be translated for the development of either preventive or more suitable treatment strategies in cancers.