家族史在预测患胰腺癌的种系致病变异携带者中的作用：多中心合作的结果。
The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration.
发表日期：2024 May 29
作者：
Eve Karloski, Beth Dudley, Brenda Diergaarde, Amie Blanco, Jessica N Everett, Elana Levinson, Tara Rangarajan, Peter P Stanich, Kimberly Childers, Sandra Brown, Christine Drogan, Giulia Martina Cavestro, Kelly Gordon, Aparajita Singh, Diane M Simeone, Hannah Reich, Fay Kastrinos, Dana Zakalik, Heather Hampel, Rachel Pearlman, Ora K Gordon, Sonia S Kupfer, Marta Puzzono, Raffaella Alessia Zuppardo, Randall E Brand
来源：
CANCER
摘要：
建议对 PDAC 易感基因中存在致病性或可能致病性变异 (PV/LPV) 的某些个体进行胰腺导管腺癌 (PDAC) 监测；该建议通常取决于 PDAC 家族史。本研究旨在描述接受基因检测的 PDAC 个体的 PDAC 家族史，以确定在这些建议中纳入家族史要求的适当性。 ATM、BRCA1、BRCA2、EPCAM、MLH1 中具有种系杂合 PV/LPV 的 PDAC 个体、MSH2、MSH6、PALB2 或 PMS2（PV/LPV 携带者）对来自 9 个机构的一级亲属 (FDR) 或二级亲属 (SDR) 的 PDAC 家族史进行了评估。还对没有种系 PV/LPV 的 PDAC 个体对照组进行了评估。该研究包括 196 名 PV/LPV 携带者和 1184 名对照者。在 PV/LPV 携带者中，25.5% 的 FDR 和/或 SDR 受影响，而对照组为 16.9% (p = .004)。与对照组相比，PV/LPV 携带者更有可能出现受影响的 FDR (p = .003)，但仅评估受影响的 SDR 时不存在统计差异 (p = .344)。大多数发生 PDAC 的 PV/LPV 携带者没有有密切的 PDAC 家族史，并且不符合当前大多数专业协会关于诊断前考虑进行 PDAC 监测的建议。然而，PV/LPV 携带者更有可能有 PDAC 家族史，尤其是受影响的 FDR。这些发现支持家族史作为 PV/LPV 携带者的风险修正因素，并强调需要确定其他风险因素。© 2024 作者。 《癌症》由 Wiley periodicals LLC 代表美国癌症协会出版。
Pancreatic ductal adenocarcinoma (PDAC) surveillance is recommended for some individuals with a pathogenic or likely pathogenic variant (PV/LPV) in a PDAC susceptibility gene; the recommendation is often dependent on family history of PDAC. This study aimed to describe PDAC family history in individuals with PDAC who underwent genetic testing to determine the appropriateness of including a family history requirement in these recommendations.Individuals with PDAC with a germline heterozygous PV/LPV in ATM, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PALB2, or PMS2 (PV/LPV carriers) were assessed for family history of PDAC in first-degree relatives (FDRs) or second-degree relatives (SDRs) from nine institutions. A control group of individuals with PDAC without a germline PV/LPV was also assessed.The study included 196 PV/LPV carriers and 1184 controls. In the PV/LPV carriers, 25.5% had an affected FDR and/or SDR compared to 16.9% in the control group (p = .004). PV/LPV carriers were more likely to have an affected FDR compared to the controls (p = .003) but there was no statistical difference when assessing only affected SDRs (p = .344).Most PV/LPV carriers who developed PDAC did not have a close family history of PDAC and would not have met most current professional societies' recommendations for consideration of PDAC surveillance before diagnosis. However, PV/LPV carriers were significantly more likely to have a family history of PDAC, particularly an affected FDR. These findings support family history as a risk modifier in PV/LPV carriers, and highlight the need to identify other risk factors.© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.