Germline multigene panel testing of patients with endometrial cancer
Status PubMed-not-MEDLINE Jazyk angličtina Země Řecko Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
37153042
PubMed Central
PMC10157349
DOI
10.3892/ol.2023.13802
PII: OL-25-6-13802
Knihovny.cz E-zdroje
- Klíčová slova
- EC, germline mutations, multigene panel testing, uterine malignancies,
- Publikační typ
- časopisecké články MeSH
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.
BIOCEV 1st Faculty of Medicine Charles University Prague 252 50 Czech Republic
Center for Medical Genetics and Reproductive Medicine Gennet Prague 170 00 Czech Republic
Department of Biochemistry Faculty of Science Charles University Prague 120 00 Czech Republic
Department of Medical Genetics Pronatal Prague 140 00 Czech Republic
Laboratory of Molecular Genetics Hospital Ceske Budejovice Ceske Budejovice 370 00 Czech Republic
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