Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.

ATM BRCA Cancer predisposition genes DNA damage repair Germline pathogenic variant Pancreatic cancer

Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
16 Jul 2024
Historique:
received: 14 03 2024
revised: 30 06 2024
accepted: 07 07 2024
medline: 20 7 2024
pubmed: 20 7 2024
entrez: 19 7 2024
Statut: aheadofprint

Résumé

Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients. Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A. 11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1-2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients. A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1-2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.

Sections du résumé

BACKGROUND AND AIM OBJECTIVE
Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.
METHODS METHODS
Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A.
RESULTS RESULTS
11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1-2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients.
CONCLUSIONS CONCLUSIONS
A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1-2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.

Identifiants

DOI: 10.1016/j.ejca.2024.114226 PMID: 39029294
pubmed: 39029294
pii: S0959-8049(24)00882-7
doi: 10.1016/j.ejca.2024.114226
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114226

Informations de copyright

Copyright © 2024 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefania Sciallero: Michele Reni: All remaining authors have declared no conflicts of interest.

Auteurs

Giulia Orsi (G)

Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Catia Carconi (C)

Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Paola Ghiorzo (P)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Paola Carrera (P)

Unit of Genomics for Human Disease Diagnosis, Laboratory of Clinical Genomics, IRCCS San Raffaele Scientific Institute, Milan, Italy; Laboratory of Clinical Molecular Genetics, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Lorenza Pastorino (L)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Silvia Presi (S)

Unit of Genomics for Human Disease Diagnosis, Laboratory of Clinical Genomics, IRCCS San Raffaele Scientific Institute, Milan, Italy; Laboratory of Clinical Molecular Genetics, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Marta Chiaravalli (M)

Oncologia medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Elena Barbieri (E)

SS Genetica Oncologica, SC Oncologia Medica, AOU Policlinico, Modena, Italy.

Guido Giordano (G)

Unit of Medical Oncology and Biomolecular Therapy, Policlinico Ospedaliero-Universitario, Foggia, Italy; Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Stefania Sciallero (S)

Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Alberto Puccini (A)

Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy.

Lisa Salvatore (L)

Oncologia medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Laura Cortesi (L)

SS Genetica Oncologica, SC Oncologia Medica, AOU Policlinico, Modena, Italy.

Marina Macchini (M)

Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Maria Iole Natalicchio (MI)

SSVD Biologia Molecolare Oncologica-PMMP, Genetica Oncologica e Farmacogenetica, Ambulatorio Tumori Eredo-Familiari, Policlinico Ospedaliero-Universitario, Foggia, Italy.

Eleonora Allavena (E)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Chiara Pirrone (C)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Livia Archibugi (L)

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Bruna Dalmasso (B)

Genetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

William Bruno (W)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Giampaolo Tortora (G)

Oncologia medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Matteo Landriscina (M)

Unit of Medical Oncology and Biomolecular Therapy, Policlinico Ospedaliero-Universitario, Foggia, Italy; Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Gabriele Capurso (G)

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Stefano Cascinu (S)

Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Massimo Falconi (M)

Pancreatic and Transplant Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Michele Reni (M)

Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: reni.michele@hsr.it.

Classifications MeSH