Figure 1.

Proposed model of cancer genetic predisposition through a micro-evolutionary perspective. Pathogenic germline variants of cancer predisposition genes (CPGs) affecting a host of cellular pathways including DNA repair, oncogenic signaling, metabolism, and cell cycle, among others, can predispose to human cancer on a spectrum from increasing mutation acquisition and cellular proliferation. While the cancer predisposition field has traditionally focused on dysfunctional DNA repair as a mechanism of carcinogenesis largely through increasing clonal diversity, we propose that additional pathways that might also confer clonal fitness advantages that are important to consider in a cancer predisposition model.