Matsubayashi Hiroyuki, Kiyozumi Yoshimi, Ono Hiroyuki
Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan.
Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.
J Hepatobiliary Pancreat Sci. 2025 Mar;32(3):212-227. doi: 10.1002/jhbp.12112. Epub 2025 Jan 15.
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.
在日本，精准癌症医学开展至今已有5年，近期在家族性胰腺癌（FPC）和遗传性胰腺癌方面的数据积累颇为显著。多基因种系检测板测试（MGPTs）显示，7%-18%的胰腺癌（PC）患者携带致病性种系变异（PGV），这一比例与乳腺癌、卵巢癌、子宫内膜癌和结直肠癌的水平相近，在FPC中发病率更高（14%-26%）。PC患者中所见的大多数PGV在临床上具有可操作性，且与同源重组（HR）途径相关（6%-10%，特别是BRCA1/2占5%-6%），临床指南建议或提议对所有PC患者进行基因检测。针对与PC风险相关的大多数遗传性综合征，已制定了共识指南，建议对PGV携带者的胰腺和其他风险器官进行监测。遗传性乳腺癌和卵巢癌（HBOC）是最常见的遗传性癌症综合征，其一生中患PC的风险呈适度上升趋势（西方国家为3%-7%）；然而，近期日本的研究显示风险水平更高（BRCA1：16%，BRCA2：14%）。此外，近期证据表明HBOC家系中PC与卵巢癌之间存在风险关联。同源重组缺陷高分提示BRCA或其他HR相关基因的双等位基因功能障碍，以及铂类药物和PARP抑制剂对PC可能有效。远程咨询和检测是未来遗传医学中可行的选择。由于PC在日本是精准癌症医学的第二大常见靶点，我们必须有效地治疗患者并管理其有风险的亲属。
