Περίληψη:
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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Fountzilas, E.
Eliades, A.
Koliou, G.-A.
Achilleos, A.
Loizides, C.
Tsangaras, K.
Pectasides, D.
Sgouros, J.
Papakostas, P.
Rallis, G.
Psyrri, A.
Papadimitriou, C.
Oikonomopoulos, G.
Ferentinos, K.
Koumarianou, A.
Zarkavelis, G.
Dervenis, C.
Aravantinos, G.
Bafaloukos, D.
Kosmidis, P.
Papaxoinis, G.
Theochari, M.
Varthalitis, I.
Kentepozidis, N.
Rigakos, G.
Saridaki, Z.
Nikolaidi, A.
Christopoulou, A.
Fostira, F.
Samantas, E.
Kypri, E.
Ioannides, M.
Koumbaris, G.
Fountzilas, G.
Patsalis, P.C.
Λέξεις-κλειδιά:
aged; Article; cancer prognosis; cancer staging; cancer survival; cancer susceptibility; clinical feature; copy number variation; family history; female; gene frequency; genetic association; genetic screening; germline mutation; heterozygote; human; indel mutation; major clinical study; male; overall survival; pancreas adenocarcinoma; prevalence; recombination repair; retrospective study
