TY - JOUR
TI - Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma
AU - Fountzilas, E.
AU - Eliades, A.
AU - Koliou, G.-A.
AU - Achilleos, A.
AU - Loizides, C.
AU - Tsangaras, K.
AU - Pectasides, D.
AU - Sgouros, J.
AU - Papakostas, P.
AU - Rallis, G.
AU - Psyrri, A.
AU - Papadimitriou, C.
AU - Oikonomopoulos, G.
AU - Ferentinos, K.
AU - Koumarianou, A.
AU - Zarkavelis, G.
AU - Dervenis, C.
AU - Aravantinos, G.
AU - Bafaloukos, D.
AU - Kosmidis, P.
AU - Papaxoinis, G.
AU - Theochari, M.
AU - Varthalitis, I.
AU - Kentepozidis, N.
AU - Rigakos, G.
AU - Saridaki, Z.
AU - Nikolaidi, A.
AU - Christopoulou, A.
AU - Fostira, F.
AU - Samantas, E.
AU - Kypri, E.
AU - Ioannides, M.
AU - Koumbaris, G.
AU - Fountzilas, G.
AU - Patsalis, P.C.
JO - Blood cancer journal
PY - 2021
VL - 13
TODO - 2
SP - 1-13
PB - MDPI AG
SN - null
TODO - 10.3390/cancers13020198
TODO - 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
TODO - 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.
ER -