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Article

Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients

1
Center for Medical Genetics, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium
2
Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium
3
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
4
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic
5
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic
6
Center of Medical Genetics UZA/UA, Antwerp University Hospital, 2000 Antwerp, Belgium
7
Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic
8
Digestive Oncology Unit, University Hospital Gasthuisberg, 3000 Leuven, Belgium
9
Department of Clinical Genetics, Maastricht University Medical Centre, 6229 GR Maastricht, The Netherlands
10
GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands
11
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic
12
Department of Gastroenterology, Ghent University Hospital, 9000 Ghent, Belgium
*
Authors to whom correspondence should be addressed.
The authors contributed equally to this work.
Academic Editor: Sanjay Gupta
Cancers 2021, 13(17), 4430; https://doi.org/10.3390/cancers13174430
Received: 16 July 2021 / Revised: 24 August 2021 / Accepted: 27 August 2021 / Published: 2 September 2021
(This article belongs to the Special Issue New Insights into Hereditary Cancer Syndromes)
We performed genetic analysis of 53 cancer predisposing genes in Belgian and Czech pancreatic cancer patients. In known pancreatic cancer predisposing genes, a high mutation detection ratio was observed in patients with multiple primary tumors and/or a family history of pancreatic or breast, ovarian or colon cancer or melanoma. BRCA1, BRCA2, and ATM were most frequently affected. Pathogenic variants in cancer predisposition genes for which the association with pancreatic cancer has not been firmly established, were less frequent, except for CHEK2. This observation warrants further analyses in other populations. To accurately determine risk associations our study highlights the importance of using a geographically-matched control population.
(1) Background: The proportion and spectrum of germline pathogenic variants (PV) associated with an increased risk for pancreatic ductal adenocarcinoma (PDAC) varies among populations. (2) Methods: We analyzed 72 Belgian and 226 Czech PDAC patients by multigene panel testing. The prevalence of pathogenic variants (PV) in relation to personal/family cancer history were evaluated. PDAC risks were calculated using both gnomAD-NFE and population-matched controls. (3) Results: In 35/298 (11.7%) patients a PV in an established PDAC-predisposition gene was found. BRCA1/2 PV conferred a high risk in both populations, ATM and Lynch genes only in the Belgian subgroup. PV in other known PDAC-predisposition genes were rarer. Interestingly, a high frequency of CHEK2 PV was observed in both patient populations. PV in PDAC-predisposition genes were more frequent in patients with (i) multiple primary cancers (12/38; 32%), (ii) relatives with PDAC (15/56; 27%), (iii) relatives with breast/ovarian/colorectal cancer or melanoma (15/86; 17%) but more rare in sporadic PDAC (5/149; 3.4%). PV in homologous recombination genes were associated with improved overall survival (HR = 0.51; 95% CI 0.34–0.77). (4) Conclusions: Our analysis emphasizes the value of multigene panel testing in PDAC patients, especially in individuals with a positive family cancer history, and underlines the importance of population-matched controls for risk assessment. View Full-Text
Keywords: pancreatic ductal adenocarcinoma; overall survival; multigene panel testing; family history; germline pancreatic ductal adenocarcinoma; overall survival; multigene panel testing; family history; germline
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Figure 1

MDPI and ACS Style

Wieme, G.; Kral, J.; Rosseel, T.; Zemankova, P.; Parton, B.; Vocka, M.; Van Heetvelde, M.; Kleiblova, P.; Blaumeiser, B.; Soukupova, J.; van den Ende, J.; Nehasil, P.; Tejpar, S.; Borecka, M.; Gómez García, E.B.; Blok, M.J.; Safarikova, M.; Kalousova, M.; Geboes, K.; De Putter, R.; Poppe, B.; De Leeneer, K.; Kleibl, Z.; Janatova, M.; Claes, K.B.M. Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients. Cancers 2021, 13, 4430. https://doi.org/10.3390/cancers13174430

AMA Style

Wieme G, Kral J, Rosseel T, Zemankova P, Parton B, Vocka M, Van Heetvelde M, Kleiblova P, Blaumeiser B, Soukupova J, van den Ende J, Nehasil P, Tejpar S, Borecka M, Gómez García EB, Blok MJ, Safarikova M, Kalousova M, Geboes K, De Putter R, Poppe B, De Leeneer K, Kleibl Z, Janatova M, Claes KBM. Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients. Cancers. 2021; 13(17):4430. https://doi.org/10.3390/cancers13174430

Chicago/Turabian Style

Wieme, Greet, Jan Kral, Toon Rosseel, Petra Zemankova, Bram Parton, Michal Vocka, Mattias Van Heetvelde, Petra Kleiblova, Bettina Blaumeiser, Jana Soukupova, Jenneke van den Ende, Petr Nehasil, Sabine Tejpar, Marianna Borecka, Encarna B. Gómez García, Marinus J. Blok, Marketa Safarikova, Marta Kalousova, Karen Geboes, Robin De Putter, Bruce Poppe, Kim De Leeneer, Zdenek Kleibl, Marketa Janatova, and Kathleen B.M. Claes 2021. "Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients" Cancers 13, no. 17: 4430. https://doi.org/10.3390/cancers13174430

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