Prostate cancer is one of the major causes of morbidity and mortality in men worldwide. Germline testing is a central feature of prostate cancer treatment, management, and hereditary cancer assessment. The percentage of patients with germline mutations in DNA repair genes ranges from 4.6% in localized disease to 11.8% to 16.2% in metastatic disease. Genetic results inform options and strategies for targeted treatment, therapeutic planning, and clinical trials in the metastatic setting. In addition, the identification of carriers of germline genetic variation associated with increased risk of prostate cancer enables targeted screening and early detection.
Hereditary renal cell carcinoma account for 5% to 8% of kidney cancers. There are several well-defined hereditary renal cell carcinoma syndromes, including von Hippel-Lindau disease, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, Birt-Hogg-Dubé syndrome, tuberous sclerosis, Cowden syndrome, microphthalmia associated transcription factor, and hereditary paraganglioma/pheochromocytoma. Although these syndromes have similarities, they vary in histology, aggressiveness, penetrance, and associated clinical manifestations. It is important to identify patients at risk for hereditary renal cell carcinoma, as it may influence care (e.g. partial versus radical nephrectomy and surveillance strategies) and optimize specific screening for family members at risk to enable early detection.
While the majority of urothelial carcinomas are chemically induced by smoking and occupational exposure to aromatic amines, mounting evidence from genetic studies have demonstrated a small, but consistent impact of inherited gene variants and family history in their development. Urothelial carcinomas are known component cancers of Lynch syndrome, which is caused by pathogenic variants in mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). The role of germline testing for urothelial carcinoma has increased, with growing precision treatment implications and gene-specific management recommendations for carriers of germline variants related to increased risk of cancer.
The Igenomix Urologic Cancer Precision Panel is indicated in those cases where the physician is suspecting of a hereditary cancer syndrome. It is designed to diagnose adults with a personal or family history suggestive of inherited cancer in an organ of the urologic system, providing important information that may impact cancer treatment as well as cancer risk assessment and management.
Chang, D. W., Gu, J., & Wu, X. (2012). Germline prognostic markers for urinary bladder cancer: obstacles and opportunities. Urologic oncology, 30(4), 524–532. https://doi.org/10.1016/j.urolonc.2012.04.003
Lenis, A. T., Lec, P. M., Chamie, K., & Mshs, M. D. (2020). Bladder Cancer: A Review. JAMA, 324(19), 1980–1991. https://doi.org/10.1001/jama.2020.17598
Pandey J, Syed W. Renal Cancer. [Updated 2021 Dec 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558975/
Chang, A. J., Autio, K. A., Roach, M., 3rd, & Scher, H. I. (2014). High-risk prostate cancer-classification and therapy. Nature reviews. Clinical oncology, 11(6), 308–323. https://doi.org/10.1038/nrclinonc.2014.68
Sokolova, A., & Cheng, H. (2021). Germline Testing in Prostate Cancer: When and Who to Test. Oncology (Williston Park, N.Y.), 35(10), 645–653. https://doi.org/10.46883/ONC.2021.3510.0645
Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma. Genetics in Medicine volume 22, pages709–718 (2020).
Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019. https://doi.org/10.1200/JCO.20.00046
Germline and Somatic Mutations in Prostate Cancer for the Clinician J Natl Compr Canc Netw 2019;17(5):515–521 doi: 10.6004/jnccn.2019.7307
Genetic Predisposition to Renal Cell Carcinoma: Implications for Counseling, Testing, Screening, and Management. J Clin Oncol 36:3560-3566. © 2018
