Clinical Significance of Germline Cancer Predisposing Variants in Unselected Patients with Pancreatic Adenocarcinoma
Year: 2021
Type: article
Study design: Observational Study
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.
Source: Cancers
Authors: 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
Institutions: European University Cyprus, Euromedica, Medicover Genetics (Cyprus), Hellenic Cooperative Oncology Group, Hippocration General Hospital, Aristotle University of Thessaloniki, Papageorgiou General Hospital, National and Kapodistrian University of Athens, University General Hospital Attikon, Aretaeio Hospital, Metropolitan Hospital, University of Ioannina, University Hospital of Ioannina, Agia Olga Hospital, Hygeia Hospital, St Savas Hospital, Laiko General Hospital of Athens, Chania General Hospital ”St. George”, Hellenic Airforce General Hospital, Mitera Hospital, National Centre of Scientific Research "Demokritos", University of Nicosia
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,376
OpenAlex ID: W3119085705