@article{3076668,
    title = "Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma",
    author = "Fountzilas, E. and Eliades, A. and Koliou, G.-A. and Achilleos, A. and Loizides, C. and Tsangaras, K. and Pectasides, D. and Sgouros, J. and Papakostas, P. and Rallis, G. and Psyrri, A. and Papadimitriou, C. and Oikonomopoulos, G. and Ferentinos, K. and Koumarianou, A. and Zarkavelis, G. and Dervenis, C. and Aravantinos, G. and Bafaloukos, D. and Kosmidis, P. and Papaxoinis, G. and Theochari, M. and Varthalitis, I. and Kentepozidis, N. and Rigakos, G. and Saridaki, Z. and Nikolaidi, A. and Christopoulou, A. and Fostira, F. and Samantas, E. and Kypri, E. and Ioannides, M. and Koumbaris, G. and Fountzilas, G. and Patsalis, P.C.",
    journal = "Blood cancer journal",
    year = "2021",
    volume = "13",
    number = "2",
    pages = "1-13",
    publisher = "MDPI AG",
    doi = "10.3390/cancers13020198",
    keywords = "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",
    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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland."
}