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

Abstract 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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fc011ae6b1b4fdcabeb4fe468c8545c
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spelling	oai:doaj.org-article:2fc011ae6b1b4fdcabeb4fe468c8545c2021-12-02T18:50:59ZPrevalence 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 cancer10.1038/s41598-020-70449-52045-2322https://doaj.org/article/2fc011ae6b1b4fdcabeb4fe468c8545c2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70449-5https://doaj.org/toc/2045-2322Abstract 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.Tiffiney R. HartmanElena V. DemidovaRandy W. LeshLily HoangMarcy RichardsonAndrea FormanLisa KesslerVirginia SpeareErica A. GolemisMichael J. HallMary B. DalySanjeevani AroraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 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
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Tiffiney R. Hartman
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/2fc011ae6b1b4fdcabeb4fe468c8545c
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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

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