Clinical Significance of Germline Cancer Predisposing Variants in Unselected Patients with Pancreatic Adenocarcinoma

Cancers

Zacharenia Saridaki¹  Nikolaos Kentepozidis²  Grigorios Rallis³  George Zarkavelis⁴  Konstantinos Ferentinos⁵  George Fountzilas⁵  Dimitrios Bafaloukos⁶  Maria Theochari⁷  Christos Dervenis⁸  Anna Koumarianou⁹  Athina Christopoulou^1,10  Florentia Fostira^1,11  Charalambos Loizides^1,12  Achilleas Achilleos^1,12  Alexia Eliades^1,12  Kyriakos Tsangaras^1,12  Elena Kypri^1,12  PhilipposC. Patsalis^1,12  George Koumbaris^1,12  Marios Ioannides^1,12  Adamantia Nikolaidi^1,13  Ioannis Varthalitis^1,14  Dimitrios Pectasides^1,15  Christos Papadimitriou^1,16  Pavlos Papakostas^1,17  George Papaxoinis^1,18  Gerasimos Aravantinos^1,19  Elena Fountzilas^2,20  Paris Kosmidis^2,21  Georgios Oikonomopoulos^2,22  Georgia-Angeliki Koliou^2,23  Amanda Psyrri^2,24  Epaminontas Samantas^2,25  Joseph Sgouros^2,25  Georgios Rigakos^2,26 

[1] Asklepios Oncology Department, 71303 Heraklion, Crete, Greece;Department of Medical Oncology, 251 Airforce General Hospital, 11525 Athens, Greece;Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, 56429 Thessaloniki, Greece;Department of Medical Oncology, University Hospital of Ioannina, Medical School, 45500 Ioannina, Greece;Department of Radiation Oncology, German Oncology Center, European University Cyprus, 4108 Limassol, Cyprus;First Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, Greece;First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11528 Athens, Greece;First Department of Surgery, General Hospital Konstantopouleio Agia Olga, 14233 Athens, Greece;Fourth Department of Internal Medicine, Hematology-Oncology Unit, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece;Medical Oncology Unit, S. Andrew Hospital, 26335 Patras, Greece;Molecular Diagnostics Laboratory, InRASTES, National Centre for Scientific Research “Demokritos”, 15341 Athens, Greece;NIPD Genetics Limited, 2409 Nicosia, Cyprus;Oncology Clinic, Mitera Hospital, 15123 Athens, Greece;Oncology Department, General Hospital of Chania, 73300 Crete, Greece;Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, 11527 Athens, Greece;Oncology Unit, Aretaieion Hospital, National and Kapodistrian University of Athens School of Medicine, 11528 Athens, Greece;Oncology Unit, Hippokration Hospital, 11527 Athens, Greece;Second Department of Internal Medicine, Agios Savvas Cancer Hospital, 11522 Athens, Greece;Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece;Second Department of Medical Oncology, Euromedica General Clinic of Thessaloniki, 54645 Thessaloniki, Greece;Second Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece;Second Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, Greece;Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, 11526 Athens, Greece;Section of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, Faculty of Medicine, National and Kapodistrian University of Athens School of Medicine, 12462 Athens, Greece;Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece;Third Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece;

关键词: BRCA2;    inherited;    overall survival;    predictive;    prognostic;   

DOI  :  10.3390/cancers13020198

来源: DOAJ

【 摘 要 】

Our aim was to determine the prevalence, prognostic and predictive role of germline pathogenic/likely pathogenic variants (P/LPVs) in cancer predisposing genes in patients with pancreatic ductal adenocarcinoma (PDAC). Germline testing of 62 cancer susceptibility genes was performed on unselected patients diagnosed from 02/2003 to 01/2020 with PDAC, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated Centers. The main endpoints were prevalence of P/LPVs and overall survival (OS). P/LPVs in PDAC-associated and homologous recombination repair (HRR) genes were identified in 22 (4.0%) and 42 (7.7%) of 549 patients, respectively. P/LPVs were identified in 16 genes, including ATM (11, 2.0%) and BRCA2 (6, 1.1%), while 19 patients (3.5%) were heterozygotes for MUTYH P/LPVs and 9 (1.6%) carried the low-risk allele, CHEK2 p.(Ile157Thr). Patients carrying P/LPVs had improved OS compared to non-carriers (22.6 vs. 13.9 months, p = 0.006). In multivariate analysis, there was a trend for improved OS in P/LPV carriers (p = 0.063). The interaction term between platinum exposure and mutational status of HRR genes was not significant (p-value = 0.35). A significant proportion of patients with PDAC carries clinically relevant germline P/LPVs, irrespectively of age, family history or disease stage. The predictive role of these P/LPVs has yet to be defined. ClinicalTrials.gov Identifier: NCT03982446.

【 授权许可】

Unknown