Cancers (Jan 2021)
Clinical Significance of Germline Cancer Predisposing Variants in Unselected Patients with Pancreatic Adenocarcinoma
- Elena Fountzilas,
- Alexia Eliades,
- Georgia-Angeliki Koliou,
- Achilleas Achilleos,
- Charalambos Loizides,
- Kyriakos Tsangaras,
- Dimitrios Pectasides,
- Joseph Sgouros,
- Pavlos Papakostas,
- Grigorios Rallis,
- Amanda Psyrri,
- Christos Papadimitriou,
- Georgios Oikonomopoulos,
- Konstantinos Ferentinos,
- Anna Koumarianou,
- George Zarkavelis,
- Christos Dervenis,
- Gerasimos Aravantinos,
- Dimitrios Bafaloukos,
- Paris Kosmidis,
- George Papaxoinis,
- Maria Theochari,
- Ioannis Varthalitis,
- Nikolaos Kentepozidis,
- Georgios Rigakos,
- Zacharenia Saridaki,
- Adamantia Nikolaidi,
- Athina Christopoulou,
- Florentia Fostira,
- Epaminontas Samantas,
- Elena Kypri,
- Marios Ioannides,
- George Koumbaris,
- George Fountzilas,
- Philippos C. Patsalis
Affiliations
- Elena Fountzilas
- Second Department of Medical Oncology, Euromedica General Clinic of Thessaloniki, 54645 Thessaloniki, Greece
- Alexia Eliades
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- Georgia-Angeliki Koliou
- Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, 11526 Athens, Greece
- Achilleas Achilleos
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- Charalambos Loizides
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- Kyriakos Tsangaras
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- Dimitrios Pectasides
- Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, 11527 Athens, Greece
- Joseph Sgouros
- Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece
- Pavlos Papakostas
- Oncology Unit, Hippokration Hospital, 11527 Athens, Greece
- Grigorios Rallis
- Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, 56429 Thessaloniki, Greece
- Amanda Psyrri
- 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
- Christos Papadimitriou
- Oncology Unit, Aretaieion Hospital, National and Kapodistrian University of Athens School of Medicine, 11528 Athens, Greece
- Georgios Oikonomopoulos
- Second Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, Greece
- Konstantinos Ferentinos
- Department of Radiation Oncology, German Oncology Center, European University Cyprus, 4108 Limassol, Cyprus
- Anna Koumarianou
- Fourth Department of Internal Medicine, Hematology-Oncology Unit, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece
- George Zarkavelis
- Department of Medical Oncology, University Hospital of Ioannina, Medical School, 45500 Ioannina, Greece
- Christos Dervenis
- First Department of Surgery, General Hospital Konstantopouleio Agia Olga, 14233 Athens, Greece
- Gerasimos Aravantinos
- Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece
- Dimitrios Bafaloukos
- First Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, Greece
- Paris Kosmidis
- Second Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece
- George Papaxoinis
- Second Department of Internal Medicine, Agios Savvas Cancer Hospital, 11522 Athens, Greece
- Maria Theochari
- First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11528 Athens, Greece
- Ioannis Varthalitis
- Oncology Department, General Hospital of Chania, 73300 Crete, Greece
- Nikolaos Kentepozidis
- Department of Medical Oncology, 251 Airforce General Hospital, 11525 Athens, Greece
- Georgios Rigakos
- Third Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece
- Zacharenia Saridaki
- Asklepios Oncology Department, 71303 Heraklion, Crete, Greece
- Adamantia Nikolaidi
- Oncology Clinic, Mitera Hospital, 15123 Athens, Greece
- Athina Christopoulou
- Medical Oncology Unit, S. Andrew Hospital, 26335 Patras, Greece
- Florentia Fostira
- Molecular Diagnostics Laboratory, InRASTES, National Centre for Scientific Research “Demokritos”, 15341 Athens, Greece
- Epaminontas Samantas
- Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece
- Elena Kypri
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- Marios Ioannides
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- George Koumbaris
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- George Fountzilas
- Department of Radiation Oncology, German Oncology Center, European University Cyprus, 4108 Limassol, Cyprus
- Philippos C. Patsalis
- NIPD Genetics Limited, 2409 Nicosia, Cyprus
- DOI
- https://doi.org/10.3390/cancers13020198
- Journal volume & issue
-
Vol. 13,
no. 2
p. 198
Abstract
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.
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