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Association of Germline Variants in Human DNA Damage Repair Genes and Response to Adjuvant Chemotherapy in Resected Pancreatic Ductal Adenocarcinoma.

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机构： [1]Department of Biliary Surgery, West China Hospital of Sichuan University, Sichuan, China [2]Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD [3]The Pancreatic Cancer Precision Medicine Center of Excellence, Baltimore, MD [4]Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China [5]Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD [6]Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD [7]Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD [8]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD [9]The Skip Viragh Center for Pancreas Cancer, Baltimore, MD [10]The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD

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关键词： Pancreatic ductal adenocarcinoma DNA damage repair chemotherapy

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The frequency and significance of the germline variants in DNA damage repair genes still need to be elucidated in patients with sporadic pancreatic ductal adenocarcinoma (PDAC). Our purpose was to determine whether germline variants in DNA damage repair genes were associated with survival of patients with sporadic PDAC. We retrospectively identified 854 patients with sporadic PDAC with germline DNA sequenced in targeted 22 DNA damage repair genes by next-generation sequencing. Outcomes were compared in terms of clinicopathologic features, disease-free survival (DFS) and overall survival (OS). Nineteen patients had deleterious mutations; 103 had variant(s) of unknown significance (VUS). Germline DNA damage repair deleterious variant carriers had superior DFS (median, 19.1 months vs. 11.9 months, p=0.012) and OS (median, 29.7 months vs. 20.2 months, p=0.034) as compared with wild-type patients. Germline DNA damage repair VUS variant carriers also had superior DFS when compared with wild-type patients. In subgroup analysis, this improved survival was limited to patients receiving adjuvant chemotherapy, deleterious variant carriers vs. wild-type patients DFS (median, 36.3 months vs. 13.1 months, p=0.006) and OS (median, 43.7 months vs. 24.3 months, p=0.045), VUS variant carriers vs. wild-type patients DFS (16.5 months vs. 13.1 months, p=0.007). Having a deleterious variant in a DNA damage repair gene is associated with improved survival after resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma. Copyright © 2020. Published by Elsevier Inc.

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出版当年[2020]版：

大类 | 1 区

医学

小类 | 1 区外科

最新[2023]版：

大类 | 2 区医学

小类 | 1 区外科

第一作者：

第一作者机构： [1]Department of Biliary Surgery, West China Hospital of Sichuan University, Sichuan, China [2]Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD [3]The Pancreatic Cancer Precision Medicine Center of Excellence, Baltimore, MD

通讯作者：

通讯机构： [2]Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD [3]The Pancreatic Cancer Precision Medicine Center of Excellence, Baltimore, MD [8]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD [*1]Department of Surgery, The Pancreatic Cancer Precision Medicine Center of Excellence, The Sidney Kimmel Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, 600 N. Wolfe

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Association of Germline Variants in Human DNA Damage Repair Genes and Response to Adjuvant Chemotherapy in Resected Pancreatic Ductal Adenocarcinoma.

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