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Hartman TR , Demidova EV , Lesh RW , Hoang L , Richardson M , Forman A , Kessler L , Speare V , Golemis EA , Hall MJ , Daly MB , Arora S
Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer
Sci Rep. 2020 Aug 11;10(1) :13518
PMID: 32782288   
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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, <‚ÄČ50% 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.
2045-2322 Hartman, Tiffiney R Demidova, Elena V Lesh, Randy W Hoang, Lily Richardson, Marcy Forman, Andrea Kessler, Lisa Speare, Virginia Golemis, Erica A Hall, Michael J Daly, Mary B Arora, Sanjeevani Dk108195/nih r01/ CA006927/NCI Core Grant P30/ W81xwh-18-1-0148/dod/ Journal Article Sci Rep. 2020 Aug 11;10(1):13518. doi: 10.1038/s41598-020-70449-5.