Center for Cancer Prevention and Detection, National Cancer Center, Goyang, Korea.
Targeted Therapy Branch, Center for Rare Cancers, National Cancer Center, Goyang, Korea.
Cancer Res Treat. 2023 Oct;55(4):1303-1312. doi: 10.4143/crt.2023.291. Epub 2023 Apr 3.
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.
胰腺导管腺癌（PDAC）的遗传归因率为 5%-10%。然而，韩国 PDAC 患者种系致病性变异（PV）的发生率尚未得到彻底研究。因此，我们研究了 PDAC 患者的风险因素和 PV 患病率，以制定未来的治疗策略。
共纳入 300 名（155 名男性）中位年龄为 65 岁（范围 33-90 岁）的韩国国家癌症中心患者。分析了癌症易感性基因、临床病理特征和癌症家族史。
在 20 名患者（6.7%，中位年龄 65 岁）中检测到 PV，分别为 ATM（n=7，31.8%）、BRCA1（n=3，13.6%）、BRCA2（n=3）和 RAD51D（n=3）。每位患者均存在 TP53、PALB2、PMS2、RAD50、MSH3 和 SPINK1 的 PV。其中，ATM 和 RAD51D 各有 1 个疑似 PV。12 名患者有各种类型癌症（包括胰腺癌）的家族史。3 名携带 ATM PV 的患者和 1 名携带 BRCA2、MSH3 和 RAD51D 三种种系 PV 的患者，其一级亲属患有胰腺癌。家族性胰腺癌史和 PV 检测有显著关联（4/20，20% vs. 16/264，5.7%；p=0.035）。
本研究表明，ATM、BRCA1、BRCA2 和 RAD51D 的种系 PV 在韩国 PDAC 患者中最为常见，与不同种族群体相当。尽管本研究未为韩国 PDAC 患者制定种系易感性基因检测指南，但它强调了对所有 PDAC 患者进行种系检测的必要性。
