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

Fountzilas, Elena and Eliades, Alexia and Koliou, Georgia-Angeliki and Achilleos, Achilleas and Loizides, Charalambos and Tsangaras, Kyriakos and Pectasides, Dimitrios and Sgouros, Joseph and Papakostas, Pavlos and Rallis, Grigorios and Psyrri, Amanda and Papadimitriou, Christos and Oikonomopoulos, Georgios and Ferentinos, Konstantinos and Koumarianou, Anna and Zarkavelis, George and Dervenis, Christos and Aravantinos, Gerasimos and Bafaloukos, Dimitrios and Kosmidis, Paris and Papaxoinis, George and Theochari, Maria and Varthalitis, Ioannis and Kentepozidis, Nikolaos and Rigakos, Georgios and Saridaki, Zacharenia and Nikolaidi, Adamantia and Christopoulou, Athina and Fostira, Florentia and Samantas, Epaminontas and Kypri, Elena and Ioannides, Marios and Koumbaris, George and Fountzilas, George and Patsalis, Philippos C. (2021) Clinical Significance of Germline Cancer Predisposing Variants in Unselected Patients with Pancreatic Adenocarcinoma. Cancers, 13 (2). p. 198. ISSN 2072-6694

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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.

Item Type: Article
Subjects: Journal Eprints > Medical Science
Depositing User: Managing Editor
Date Deposited: 18 Jan 2023 11:10
Last Modified: 31 Jul 2024 12:23
URI: http://repository.journal4submission.com/id/eprint/1250

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