Dataset Information

Germline multigene panel testing of patients with endometrial cancer.

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=1.8×10^-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.

SUBMITTER: Kral J

PROVIDER: S-EPMC10157349 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Germline multigene panel testing of patients with endometrial cancer.

Kral Jan J Jelinkova Sandra S Zemankova Petra P Vocka Michal M Borecka Marianna M Cerna Leona L Cerna Marta M Dostalek Lukas L Duskova Petra P Foretova Lenka L Havranek Ondrej O Horackova Klara K Hovhannisyan Milena M Chvojka Stepan S Kalousova Marta M Kosarova Marcela M Koudova Monika M Krutilkova Vera V Machackova Eva E Nehasil Petr P Novotny Jan J Otahalova Barbora B Puchmajerova Alena A Safarikova Marketa M Slama Jiri J Stranecky Viktor V Subrt Ivan I Tavandzis Spiros S Zikan Michal M Zima Tomas T Soukupova Jana J Kleiblova Petra P Kleibl Zdenek Z Janatova Marketa M

Oncology letters 20230412 6

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 candida ...[more]

PMID: 37153042

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Project description:BackgroundLittle is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs).MethodsStudy participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA).ResultsThe mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences.ConclusionsIn a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds.Lay summaryMultigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

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Germline multigene panel testing of patients with endometrial cancer.

Publications

Germline multigene panel testing of patients with endometrial cancer.

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