Open Access

Germline multigene panel testing of patients with endometrial cancer

  • Authors:
    • Jan Kral
    • Sandra Jelinkova
    • Petra Zemankova
    • Michal Vocka
    • Marianna Borecka
    • Leona Cerna
    • Marta Cerna
    • Lukas Dostalek
    • Petra Duskova
    • Lenka Foretova
    • Ondrej Havranek
    • Klara Horackova
    • Milena Hovhannisyan
    • Stepan Chvojka
    • Marta Kalousova
    • Marcela Kosarova
    • Monika Koudova
    • Vera Krutilkova
    • Eva Machackova
    • Petr Nehasil
    • Jan Novotny
    • Barbora Otahalova
    • Alena Puchmajerova
    • Marketa Safarikova
    • Jiri Slama
    • Viktor Stranecky
    • Ivan Subrt
    • Spiros Tavandzis
    • Michal Zikan
    • Tomas Zima
    • Jana Soukupova
    • Petra Kleiblova
    • Zdenek Kleibl
    • Marketa Janatova
  • View Affiliations

  • Published online on: April 12, 2023     https://doi.org/10.3892/ol.2023.13802
  • Article Number: 216
  • Copyright : © Kral et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

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=1.8x10‑17] 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.
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June-2023
Volume 25 Issue 6

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Copy and paste a formatted citation
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Spandidos Publications style
Kral J, Jelinkova S, Zemankova P, Vocka M, Borecka M, Cerna L, Cerna M, Dostalek L, Duskova P, Foretova L, Foretova L, et al: Germline multigene panel testing of patients with endometrial cancer. Oncol Lett 25: 216, 2023
APA
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L. ... Janatova, M. (2023). Germline multigene panel testing of patients with endometrial cancer. Oncology Letters, 25, 216. https://doi.org/10.3892/ol.2023.13802
MLA
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L., Cerna, M., Dostalek, L., Duskova, P., Foretova, L., Havranek, O., Horackova, K., Hovhannisyan, M., Chvojka, S., Kalousova, M., Kosarova, M., Koudova, M., Krutilkova, V., Machackova, E., Nehasil, P., Novotny, J., Otahalova, B., Puchmajerova, A., Safarikova, M., Slama, J., Stranecky, V., Subrt, I., Tavandzis, S., Zikan, M., Zima, T., Soukupova, J., Kleiblova, P., Kleibl, Z., Janatova, M."Germline multigene panel testing of patients with endometrial cancer". Oncology Letters 25.6 (2023): 216.
Chicago
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L., Cerna, M., Dostalek, L., Duskova, P., Foretova, L., Havranek, O., Horackova, K., Hovhannisyan, M., Chvojka, S., Kalousova, M., Kosarova, M., Koudova, M., Krutilkova, V., Machackova, E., Nehasil, P., Novotny, J., Otahalova, B., Puchmajerova, A., Safarikova, M., Slama, J., Stranecky, V., Subrt, I., Tavandzis, S., Zikan, M., Zima, T., Soukupova, J., Kleiblova, P., Kleibl, Z., Janatova, M."Germline multigene panel testing of patients with endometrial cancer". Oncology Letters 25, no. 6 (2023): 216. https://doi.org/10.3892/ol.2023.13802