Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma

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

doi:10.3390/cancers13020198

Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	198
Pages (from-to)	1-13
Number of pages	13
Journal	Cancers
Volume	13
Issue number	2
DOIs	https://doi.org/10.3390/cancers13020198
Publication status	Published - 2 Jan 2021

Keywords

BRCA2
Inherited
Overall survival
Predictive
Prognostic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers13020198

Cite this

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., ... Patsalis, P. C. (2021). Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma. Cancers, 13(2), 1-13. Article 198. https://doi.org/10.3390/cancers13020198

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title = "Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma",

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.",

keywords = "BRCA2, Inherited, Overall survival, Predictive, Prognostic",

author = "Elena Fountzilas and Alexia Eliades and Koliou, \{Georgia Angeliki\} and Achilleas Achilleos and Charalambos Loizides and Kyriakos Tsangaras and Dimitrios Pectasides and Joseph Sgouros and Pavlos Papakostas and Grigorios Rallis and Amanda Psyrri and Christos Papadimitriou and Georgios Oikonomopoulos and Konstantinos Ferentinos and Anna Koumarianou and George Zarkavelis and Christos Dervenis and Gerasimos Aravantinos and Dimitrios Bafaloukos and Paris Kosmidis and George Papaxoinis and Maria Theochari and Ioannis Varthalitis and Nikolaos Kentepozidis and Georgios Rigakos and Zacharenia Saridaki and Adamantia Nikolaidi and Athina Christopoulou and Florentia Fostira and Epaminontas Samantas and Elena Kypri and Marios Ioannides and George Koumbaris and George Fountzilas and Patsalis, \{Philippos C.\}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jan,

day = "2",

doi = "10.3390/cancers13020198",

language = "English",

volume = "13",

pages = "1--13",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "2",

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Fountzilas, E, Eliades, A, Koliou, GA, 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, PC 2021, 'Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma', Cancers, vol. 13, no. 2, 198, pp. 1-13. https://doi.org/10.3390/cancers13020198

TY - JOUR

T1 - Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma

AU - Fountzilas, Elena

AU - Eliades, Alexia

AU - Koliou, Georgia Angeliki

AU - Achilleos, Achilleas

AU - Loizides, Charalambos

AU - Tsangaras, Kyriakos

AU - Pectasides, Dimitrios

AU - Sgouros, Joseph

AU - Papakostas, Pavlos

AU - Rallis, Grigorios

AU - Psyrri, Amanda

AU - Papadimitriou, Christos

AU - Oikonomopoulos, Georgios

AU - Ferentinos, Konstantinos

AU - Koumarianou, Anna

AU - Zarkavelis, George

AU - Dervenis, Christos

AU - Aravantinos, Gerasimos

AU - Bafaloukos, Dimitrios

AU - Kosmidis, Paris

AU - Papaxoinis, George

AU - Theochari, Maria

AU - Varthalitis, Ioannis

AU - Kentepozidis, Nikolaos

AU - Rigakos, Georgios

AU - Saridaki, Zacharenia

AU - Nikolaidi, Adamantia

AU - Christopoulou, Athina

AU - Fostira, Florentia

AU - Samantas, Epaminontas

AU - Kypri, Elena

AU - Ioannides, Marios

AU - Koumbaris, George

AU - Fountzilas, George

AU - Patsalis, Philippos C.

PY - 2021/1/2

Y1 - 2021/1/2

N2 - 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.

AB - 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.

KW - BRCA2

KW - Inherited

KW - Overall survival

KW - Predictive

KW - Prognostic

UR - https://www.scopus.com/pages/publications/85099376308

U2 - 10.3390/cancers13020198

DO - 10.3390/cancers13020198

M3 - Article

AN - SCOPUS:85099376308

SN - 2072-6694

VL - 13

SP - 1

EP - 13

JO - Cancers

JF - Cancers

IS - 2

M1 - 198

ER -

Clinical significance of germline cancer predisposing variants in unselected patients with pancreatic adenocarcinoma

Abstract

Keywords

UN SDGs

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