Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations.

BRCA mutations are well established in breast and ovarian cancers and increasingly recognized in colorectal cancer (CRC), particularly BRCA1. Dual BRCA1/2 pathogenic variants in CRC remain exceptionally rare. We report a case of early-onset CRC in a young male harboring pathogenic variants in BRCA1, BRCA2, and POLE, with no personal or familial cancer history. This mutational triad suggests convergence of homologous recombination deficiency and impaired DNA proofreading, resulting in a hypermutated phenotype. The case may represent a novel molecular CRC subtype and underscores the importance of broad-panel germline testing in young patients, with implications for poly (ADP‑ribose) polymerase and immune checkpoint inhibitor therapy.