Evidence map›Paper›PMID 29961768›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019

Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer.

Matthew B Yurgelun, Anu B Chittenden, Vicente Morales-Oyarvide, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Zhi Rong Qian, Marisa W Welch, Lauren K Brais, Annacarolina Da Silva and 28 more

Abstract read
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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 7 pooled it
10.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 7 syntheses or guidelines pooled it, 214 citations in OpenAlex.

  1. Guideline
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  5. Homologous Recombination Deficiency in Pancreatic Cancer: A Systematic Review and Prevalence Meta-Analysis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Pooled it
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  8. A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
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  15. Pancreatic cancer.Nature reviews. Disease primers · 2026
    Review
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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 8 institutions in 1 country.

Matthew B Yurgelun *Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu.
Anu B Chittenden *Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Vicente Morales-Oyarvide *Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Douglas A RubinsonDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Richard F DunneDepartment of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Margaret M KozakDepartment of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA.
Zhi Rong QianDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Marisa W WelchDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Lauren K BraisDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Annacarolina Da SilvaDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Justin L BuiDepartment of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA.
Chen YuanDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Tingting LiDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Wanwan LiDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Atsuhiro MasudaDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mancang GuDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Andrea J BullockDepartment of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Daniel T ChangDepartment of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA.
Thomas E ClancyDepartment of Surgery, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
David C LinehanDepartment of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
Jennifer J Findeis-HoseyDepartment of Pathology, University of Rochester Medical Center, Rochester, NY, USA.
Leona A DoyleDepartment of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
Aaron R ThornerDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Matthew D DucarCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
Bruce M WollisonCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
Natalia KhalafDepartment of Medicine, Brigham & Women's Hospital, Boston, MA, USA.
Kimberly PerezDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Sapna SyngalDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Andrew J AguirreDepartment of Medicine, Brigham & Women's Hospital, Boston, MA, USA.
William C HahnDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Matthew L MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Charles S FuchsDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Shuji OginoDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jason L HornickDepartment of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
Aram F HezelDepartment of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Albert C KoongDepartment of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA.
Jonathan A Nowak *Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Brian M Wolpin *Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Dana-Farber Cancer Institute · USBrigham and Women's Hospital · USHarvard University · USUniversity of Rochester Medical Center · USStanford Cancer InstituteBeth Israel Deaconess Medical Center · USMassachusetts Institute of Technology · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI MAYER, ROBERT J · 2007 to 2023
$33.2M
Circulating Biomarker Consortium for Pancreatic Cancer Early DetectionU01CA210171 · NCI · DANA-FARBER CANCER INST · PI Michael H. Rosenthal, Brian Matthew Wolpin · 2016 to 2026
$8.7M
Accelerating Transdisciplinary Epidemiology of Colorectal CancerR35CA197735 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2015 to 2021
$6.0M
Validation and extension of the PREMM Model for mismatch repair gene mutationsR01CA132829 · NCI · DANA-FARBER CANCER INST · PI SYNGAL, SAPNA · 2008 to 2022
$5.6M
Prospective Cohort Collaborative in Pancreatic Cancer Epidemiology & PathogenesisR01CA124908 · NCI · DANA-FARBER CANCER INST · PI FUCHS, CHARLES S · 2007 to 2012
$4.3M
Functional interrogation of epigenetic vulnerabilities in KRAS-mutant pancreatic cancerK08CA218420 · NCI · DANA-FARBER CANCER INST · PI AGUIRRE, ANDREW JAMES · 2017 to 2021
$886k
NCI NIH HHS K08 CA218420NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA124908NCI NIH HHS R01 CA132829NCI NIH HHS R35 CA197735NCI NIH HHS U01 CA210171
6 · The paper itself

Abstract

purposeGermline variants in double-strand DNA damage repair (dsDDR) genes (e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP) inhibitors. We sought to determine the prevalence and significance of germline cancer susceptibility gene variants in PDAC with paired somatic and survival analyses.

methodsUsing a customized next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC ascertained without preselection for high-risk features (e.g., young age, personal/family history). All identified variants were assessed for pathogenicity. Outcomes were analyzed using multivariable-adjusted Cox proportional hazards regression.

resultsWe found that 28/289 (9.7%; 95% confidence interval [CI] 6.5-13.7%) patients carried pathogenic/likely pathogenic germline variants, including 21 (7.3%) dsDDR gene variants (3 BRCA1, 4 BRCA2, 14 other dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), 3 Lynch syndrome, and 4 other genes (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry identified second hits in the tumor in 12/27 (44.4%) patients with germline variants (1 failed sequencing). Compared with noncarriers, patients with germline dsDDR gene variants had superior overall survival (hazard ratio [HR] 0.54; 95% CI 0.30-0.99; P = 0.05).

conclusionNearly 10% of PDAC patients harbor germline variants, although the majority lack somatic second hits, the therapeutic significance of which warrants further study.

Indexed as

Genetic Predisposition to DiseaseAdenocarcinomaAdultAgedDisease-Free SurvivalDNA Breaks, Double-StrandedEthnicityFemaleGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedNeoplasm ProteinsPancreatic NeoplasmsNeoplasm ProteinsFamilial pancreatic cancerHereditary breast and ovarian cancerLynch syndromePARP inhibitors

Identifiers

PMID29961768
PMCPMC6666401
OpenAlexW2810883871

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.