Pathogenic variants (PVs) in multiple genes are known to increase the risk of early-onset renal cancer (eoRC). However, many eoRC patients lack PVs in RC-specific genes; thus, their genetic risk remains undefined. Here, we determine if PVs in DNA damage response and repair (DDRR) genes are enriched in eoRC patients undergoing cancer risk assessment. Retrospective review of de-identified results from 844 eoRC patients, undergoing testing with a multi-gene panel, for a variety of indications, by Ambry Genetics. PVs in cancer-risk genes were identified in 12.8% of patients-with 3.7% in RC-specific, and 8.55% in DDRR genes. DDRR gene PVs were most commonly identified in CHEK2, BRCA1, BRCA2, and ATM. Among the 2.1% of patients with a BRCA1 or BRCA2 PV, < 50% reported a personal history of hereditary breast or ovarian-associated cancer. No association between age of RC diagnosis and prevalence of PVs in RC-specific or DDRR genes was observed. Additionally, 57.9% patients reported at least one additional cancer; breast cancer being the most common (40.1% of females, 2.5% of males). Multi-gene testing including DDRR genes may provide a more comprehensive risk assessment in eoRC patients. Further validation is needed to characterize the association with eoRC.
Scientific reports. 2020 Aug 11*** epublish ***
Tiffiney R Hartman, Elena V Demidova, Randy W Lesh, Lily Hoang, Marcy Richardson, Andrea Forman, Lisa Kessler, Virginia Speare, Erica A Golemis, Michael J Hall, Mary B Daly, Sanjeevani Arora
Arcadia University, Glenside, PA, USA., Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA., Geisinger Commonwealth School of Medicine, Scranton, PA, USA., Ambry Genetics, Konica Minolta, Aliso Viejo, CA, USA., Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA., Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA., Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA. .