Homologous recombination (HR) is a highly accurate DNA repair mechanism. Several HR genes are established cancer susceptibility genes with clinically actionable pathogenic variants (PVs). Classically, BRCA1 and BRCA2 germline PVs are associated with significant breast and ovarian cancer risks. Patients with BRCA1/BRCA2 PVs display worse clinical outcomes but respond better to platinum-based chemotherapies and PARP inhibitors, a trait termed as "BRCAness". With the advent of whole-exome sequencing and multigene panels, PVs in other HR genes are increasingly identified among familial cancers. As such, several genes such as PALB2 are reclassified as cancer predisposition genes. But, evidence for cancer risks remains unclear for many others. In this review, we will discuss the cancer predispositions and treatment implications beyond BRCA1/BRCA2, with a focus on 24 HR genes: 53BP1, ATM,
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