Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms.

Adult Aged Aged, 80 and over Ataxia Telangiectasia Mutated Proteins / genetics Carcinoma, Pancreatic Ductal / genetics Case-Control Studies Female Genetic Predisposition to Disease Germ-Line Mutation Humans Male Middle Aged Neoplasm Grading Neoplasms, Multiple Primary / genetics Pancreatic Intraductal Neoplasms / genetics Pancreatic Neoplasms / genetics Patched-1 Receptor / genetics Repressor Proteins / genetics Retrospective Studies Risk Factors
Cancer Genetics Pancreas Predisposition

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
05 2019
Historique:
received: 11 10 2018
revised: 11 01 2019
accepted: 23 01 2019
pubmed: 5 2 2019
medline: 14 5 2019
entrez: 5 2 2019
Statut: ppublish

Résumé

Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320). In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

Sections du résumé

BACKGROUND & AIMS
Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN.
METHODS
We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium.
RESULTS
We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320).
CONCLUSIONS
In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

Identifiants

DOI: 10.1053/j.gastro.2019.01.254 PMID: 30716324 PMC: PMC6475492
pubmed: 30716324
pii: S0016-5085(19)30353-1
doi: 10.1053/j.gastro.2019.01.254
pmc: PMC6475492
mid: NIHMS1520497
pii:
doi:

Substances chimiques

PTCH1 protein, human 0
Patched-1 Receptor 0
Repressor Proteins 0
SUFU protein, human 0
ATM protein, human EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1905-1913

Subventions

Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA190889
Pays : United States

Informations de copyright

Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Auteurs

Michael Skaro (M)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Neha Nanda (N)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Christian Gauthier (C)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Matthäus Felsenstein (M)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Zhengdong Jiang (Z)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Miaozhen Qiu (M)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Koji Shindo (K)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Jun Yu (J)

The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Danielle Hutchings (D)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Ammar A Javed (AA)

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Ross Beckman (R)

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Jin He (J)

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Christopher L Wolfgang (CL)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Elizabeth Thompson (E)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Ralph H Hruban (RH)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Alison P Klein (AP)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Michael Goggins (M)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Laura D Wood (LD)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Nicholas J Roberts (NJ)

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: nrobert8@jhmi.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › Protéines mutées dans l'ataxie-télangiectasie › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation germinale › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Diagnostic › Pronostic › Grading des tumeurs › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Tumeurs › Tumeurs primitives multiples › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Tumeurs intracanalaires pancréatiques › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Récepteurs patched › Récepteur Patched-1 › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Prevalence of Germline Mutations Associated...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Prevalence of Germline Mutations Associated...