Germline multigene panel testing of patients with endometrial cancer.

Autor: Kral J; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Jelinkova S; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Zemankova P; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague 120 00, Czech Republic., Vocka M; Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Borecka M; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Cerna L; Center for Medical Genetics and Reproductive Medicine, Gennet, Prague 170 00, Czech Republic., Cerna M; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Dostalek L; Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Duskova P; Laboratory of Molecular Genetics, Hospital Ceske Budejovice, Ceske Budejovice 370 00, Czech Republic., Foretova L; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno 656 53, Czech Republic., Havranek O; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; BIOCEV (Biotechnology and Biomedicine Center of The Czech Academy of Sciences and Charles University), First Faculty of Medicine, Charles University, Prague 252 50, Czech Republic., Horackova K; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Hovhannisyan M; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Chvojka S; Center for Medical Genetics and Reproductive Medicine, Gennet, Prague 170 00, Czech Republic., Kalousova M; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Kosarova M; Department of Medical Genetics, Pronatal, Prague 140 00, Czech Republic., Koudova M; Center for Medical Genetics and Reproductive Medicine, Gennet, Prague 170 00, Czech Republic., Krutilkova V; Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, Novy Jicin 741 00, Czech Republic., Machackova E; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno 656 53, Czech Republic., Nehasil P; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague 120 00, Czech Republic.; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Novotny J; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Otahalova B; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; Department of Biochemistry, Faculty of Science, Charles University, Prague 120 00, Czech Republic., Puchmajerova A; Center for Medical Genetics and Reproductive Medicine, Gennet, Prague 170 00, Czech Republic., Safarikova M; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Slama J; Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Stranecky V; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Subrt I; Department of Medical Genetics, Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, Pilsen 323 00, Czech Republic., Tavandzis S; Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, Novy Jicin 741 00, Czech Republic., Zikan M; Department of Gynecology and Obstetrics, Bulovka University Hospital and First Faculty of Medicine, Charles University, Prague 180 00, Czech Republic., Zima T; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Soukupova J; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Kleiblova P; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic., Kleibl Z; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.; Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague 120 00, Czech Republic., Janatova M; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic.
Jazyk: angličtina
Zdroj: Oncology letters [Oncol Lett] 2023 Apr 12; Vol. 25 (6), pp. 216. Date of Electronic Publication: 2023 Apr 12 (Print Publication: 2023).
DOI: 10.3892/ol.2023.13802
Abstrakt: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. The present study aimed to determine the frequency of germline pathogenic variants (PV) in patients with EC. In this multicenter retrospective cohort study, germline genetic testing (GGT) was performed in 527 patients with EC using a next generation sequencing panel targeting 226 genes, including 5 Lynch syndrome (LS) and 14 hereditary breast and ovarian cancer (HBOC) predisposition genes, and 207 candidate predisposition genes. Gene-level risks were calculated using 1,662 population-matched controls (PMCs). Patients were sub-categorized to fulfill GGT criteria for LS, HBOC, both or none. A total of 60 patients (11.4%) carried PV in LS (5.1%) and HBOC (6.6%) predisposition genes, including two carriers of double PV. PV in LS genes conferred a significantly higher EC risk [odds ratio (OR), 22.4; 95% CI, 7.8-64.3; P=1.8×10 -17 ] than the most frequently altered HBOC genes BRCA1 (OR, 3.9; 95% CI, 1.6-9.5; P=0.001), BRCA2 (OR, 7.4; 95% CI, 1.9-28.9; P=0.002) and CHEK2 (OR, 3.2; 95% CI, 1.0-9.9; P=0.04). Furthermore, >6% of patients with EC not fulfilling LS or HBOC GGT indication criteria carried a PV in a clinically relevant gene. Carriers of PV in LS genes had a significantly lower age of EC onset than non-carriers (P=0.01). Another 11.0% of patients carried PV in a candidate gene (the most frequent were FANCA and MUTYH ); however, their individual frequencies did not differ from PMCs (except for aggregated frequency of loss-of-function variants in POLE / POLD1 ; OR, 10.44; 95% CI, 1.1-100.5; P=0.012). The present study demonstrated the importance of GGT in patients with EC. The increased risk of EC of PV carriers in HBOC genes suggests that the diagnosis of EC should be included in the HBOC GGT criteria.
Competing Interests: The authors declare that they have no competing interests.
(Copyright: © Kral et al.)
Databáze: MEDLINE
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