Genetic medicine of familial and hereditary pancreatic cancer: Recent update in the era of precision cancer medicine.

In Japan, 5 years have passed since the initiation of precision cancer medicine, and recent data accumulation in familial pancreatic cancer (FPC) and hereditary pancreatic cancer is outstanding. Multigene germline panel tests (MGPTs) have revealed that 7%-18% of patients with pancreatic cancer (PC) harbor pathogenic germline variants (PGVs), almost equal to the levels of breast, ovarian, endometrial, and colorectal cancers, with a higher incidence in FPC (14%-26%). The majority of PGVs seen in PC patients are clinically actionable and associated with homologous recombination (HR) pathways (6%-10%, particularly BRCA1/2 in 5%-6%), and the clinical guidelines recommend or propose genetic testing for all PC patients. Consensus guidelines have been established for most of the hereditary syndromes associated with PC risks, and surveillances of the pancreas and other at-risk organs are recommended for PGV carriers. Hereditary breast and ovarian cancer (HBOC) is the commonest hereditary cancer syndrome that has moderately increasing life-time risks of PC (3%-7% in Western countries); however, recent Japanese research demonstrated a higher risk level (BRCA1: 16%, BRCA2: 14%). Moreover, recent evidence has suggested a risk linkage between PC and ovarian cancer in HBOC pedigrees. High scores of homologous recombination deficiency suggest biallelic dysfunction of BRCA or other HR-related genes, and the likely effectiveness of platinum agents and PARP inhibitors against PCs. Remote counseling and testing are possible option in the future genetic medicine. As PC ranks in the second commonest target of precision cancer medicine in Japan, we must treat the patients and manage their at-risk relatives efficiently.