Prevalence of pathogenic germline cancer risk variants in testicular cancer patients: Identifying high risk groups

• Published in: Urologic oncology 2022-03, Vol.40 (3), p.113.e9-113.e15
• Main Authors: Ramamurthy, Chethan, Nassar, Amin H., Abou Alaiwi, Sarah, Adib, Elio, Akl, Elie W., Yang, Shan, Esplin, Edward D., Liss, Michael A., Tomlinson, Gail E., Sonpavde, Guru P.
• Format: Article
• Language: English
• Subjects: Genetic Predisposition to Disease; Germ Cells; Germ-Line Mutation; Germline variants; Humans; Male; Neoplasms, Germ Cell and Embryonal; Prevalence; Testicular cancer; Testicular Neoplasms - epidemiology; Testicular Neoplasms - genetics
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2021.12.014

•Testicular cancer patients are at risk for carrying germline pathogenic variants.•Risk factors for germline variants include having another primary malignancy or a family history of testicular cancer.•A subset of patients with testicular cancer may particularly benefit from genetic evaluation. Germline studies in testicular cancer have focused on unselected populations but so far have not led to recommendations for testicular cancer screening. Herein, we hypothesized that men with testicular cancer and an additional risk factor for hereditary cancer predisposition carry a higher rate of pathogenic variants than men with testicular cancer without another risk factor. 187 patients with a personal history of testicular cancer underwent germline testing via Invitae. Patients were divided into low-risk and high-risk patients. Low-risk patients (n=83) had testicular cancer as their only primary malignancy without a family history of testicular cancer. High-risk patients (n=104) had additional primary malignancies and/or a family history of testicular cancer. 23.1% of patients harbored pathogenic germline variants with 19.6% carrying actionable variants. Among low-risk patients, 13.5% carried pathogenic variants versus 29.9% in the high-risk cohort. Of patients with a family history of non-testicular cancers and a personal history of additional primary malignancies, 32% harbored pathogenic variants. High-risk patients are twice as likely to harbor pathogenic variants compared to low-risk patients. Importantly, patients with a family history of cancer and other primary malignancies represent a subset of patients that may benefit from genetic evaluation.