학술논문
Germline multigene panel testing of patients with endometrial cancer
Document Type
Academic Journal
Author
Kral, Jan; Jelinkova, Sandra; Zemankova, Petra; Vocka, Michal; Borecka, Marianna; Cerna, Leona; Cerna, Marta; Dostalek, Lukas; Duskova, Petra; Foretova, Lenka; Havranek, Ondrej; Horackova, Klara; Hovhannisyan, Milena; Chvojka, Stepan; Kalousova, Marta; Kosarova, Marcela; Koudova, Monika; Krutilkova, Vera; Machackova, Eva; Nehasil, Petr; Novotny, Jan; Otahalova, Barbora; Puchmajerova, Alena; Safarikova, Marketa; Slama, Jiri; Stranecky, Viktor; Subrt, Ivan; Tavandzis, Spiros; Zikan, Michal; Zima, Tomas; Soukupova, Jana; Kleiblova, Petra; Kleibl, Zdenek; Janatova, Marketa
Source
Oncology Letters. August, 2023, Vol. 26 Issue 2, p1A, p30 p.
Subject
Language
English
ISSN
1792-1074
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, 78-64.3; P=1.8*[10.sup.-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. Key words: uterine malignancies, EC, multigene panel testing, germline mutations
Introduction Endometrial cancer (EC) is the most common gynecological malignancy in the developed countries (1). Its rate of incidence per 100,000 people in Europe was 32 and in the Czech [...]
Introduction Endometrial cancer (EC) is the most common gynecological malignancy in the developed countries (1). Its rate of incidence per 100,000 people in Europe was 32 and in the Czech [...]