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

被引：1

作者：

Orsi, Giulia ^{[1
,16
]}

Carconi, Catia ^{[1
,16
]}

Ghiorzo, Paola ^{[2
,3
]}

Carrera, Paola ^{[4
,5
]}

Pastorino, Lorenza ^{[2
,3
]}

Presi, Silvia ^{[4
,5
]}

Chiaravalli, Marta ^{[6
,7
]}

Barbieri, Elena ^{[8
,11
]}

Giordano, Guido ^{[9
,10
]}

Sciallero, Stefania ^{[11
]}

Puccini, Alberto ^{[12
]}

Salvatore, Lisa ^{[6
,7
]}

Cortesi, Laura ^{[8
,11
]}

Macchini, Marina ^{[1
,16
]}

Natalicchio, Maria Iole ^{[13
]}

Allavena, Eleonora ^{[2
,3
]}

Pirrone, Chiara ^{[2
]}

Archibugi, Livia ^{[14
]}

Dalmasso, Bruna ^{[3
]}

Bruno, William ^{[2
,3
]}

Tortora, Giampaolo ^{[6
,7
]}

Landriscina, Matteo ^{[9
,10
]}

Capurso, Gabriele ^{[14
,16
]}

Cascinu, Stefano ^{[1
,16
]}

Falconi, Massimo ^{[15
,16
]}

Reni, Michele ^{[1
,12
,16
]}

机构：

[1] IRCCS San Raffaele Sci Inst, Pancreas Translat & Clin Res Ctr, Dept Med Oncol, Via Olgettina 60, I-20132 Milan, Italy

[2] Univ Genoa, Dept Internal Med & Med Specialties DiMI, Genoa, Italy

[3] IRCCS Osped Policlin San Martino, Genet Rare Canc, Genoa, Italy

[4] IRCCS San Raffaele Sci Inst, Unit Genom Human Dis Diag, Lab Clin Genom, Milan, Italy

[5] IRCCS San Raffaele Sci Inst, Lab Clin Mol Genet, Milan, Italy

[6] Fdn Policlin Univ Agostino Gemelli IRCCS, Comprehens Canc Ctr, Oncol Med, Rome, Italy

[7] Univ Cattolica Sacro Cuore, Rome, Italy

[8] AOU Policlin, SS Genet Oncolog, SC Oncol Med, Modena, Italy

[9] Policlin Osped Univ, Unit Med Oncol & Biomol Therapy, Foggia, Italy

[10] Univ Foggia, Dept Med & Surg Sci, Foggia, Italy

[11] IRCCS Osped Policlin San Martino, Med Oncol Unit 1, Genoa, Italy

[12] IRCCS Humanitas Res Hosp, Med Oncol & Hematol Unit, Rozzano, MI, Italy

[13] Policlin Osped Univ, SSVD Biol Mol Oncolog PMMP Genet Oncol Farmacogen, Ambulatorio Tumori Eredo Familiari, Foggia, Italy

[14] IRCCS San Raffaele Sci Inst, Pancreas Translat & Clin Res Ctr, Pancreato Biliary Endoscopy & Endosonog Div, Milan, Italy

[15] IRCCS San Raffaele Sci Inst, Pancreas Translat & Clin Res Ctr, Pancreat & Transplant Surg Unit, Milan, Italy

[16] Univ Vita Salute San Raffaele, Milan, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 208卷

关键词：

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

D O I：

10.1016/j.ejca.2024.114226

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background and aim: 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: 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: 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: 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.

引用

页数：7

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