File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Germline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer

TitleGermline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer
Authors
KeywordsActive surveillance
ATM
BRCA1
BRCA2
Germline mutations
Issue Date2019
Citation
European Urology, 2019, v. 75, n. 5, p. 743-749 How to Cite?
AbstractBackground: Mutations in DNA repair genes are associated with aggressive prostate cancer (PCa). Objective: To assess whether germline mutations are associated with grade reclassification (GR) in patients undergoing active surveillance (AS). Design, setting, and participants: Two independent cohorts of PCa patients undergoing AS; 882 and 329 patients from Johns Hopkins and North Shore, respectively. Outcome measurements and statistical analysis: Germline DNA was sequenced for DNA repair genes, including BRCA1/2 and ATM (three-gene panel). Pathogenicity of mutations was defined according to the American College of Medical Genetics guidelines. Association of mutation carrier status and GR was evaluated by a competing risk analysis. Results and limitations: Of 1211, 289 patients experienced GR; 11 of 26 with mutations in a three-gene panel and 278 of 1185 noncarriers; adjusted hazard ratio (HR) = 1.96 (95% confidence interval [CI] = 1.004–3.84, p = 0.04). Reclassification occurred in six of 11 carriers of BRCA2 mutations and 283 of 1200 noncarriers; adjusted HR = 2.74 (95% CI = 1.26–5.96, p = 0.01). The carrier rates of pathogenic mutations in the three-gene panel, and BRCA2 alone, were significantly higher in those reclassified (3.8% and 2.1%, respectively) than in those not reclassified (1.6% and 0.5%, respectively; p = 0.04 and 0.03, respectively). Carrier rates for BRCA2 were greater for those reclassified from Gleason score (GS) 3 + 3 at diagnosis to GS ≥4 + 3 (4.1% vs 0.7%, p = 0.01) versus GS 3 + 4 (2.1% vs 0.6%; p = 0.03). Results are limited by the small number of mutation carriers and an intermediate end point. Conclusions: Mutation status of BRCA1/2 and ATM is associated with GR among men undergoing AS. Patient summary: Men on active surveillance with inherited mutations in BRCA1/2 and ATM are more likely to harbor aggressive prostate cancer. Men with inherited mutations in DNA repair genes (BRCA1/2 and ATM) have a greater risk of grade reclassification on active surveillance (AS) than those without. Mutation status can help inform decisions for AS.
Persistent Identifierhttp://hdl.handle.net/10722/314354
ISSN
2023 Impact Factor: 25.3
2023 SCImago Journal Rankings: 6.928
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCarter, H. Ballentine-
dc.contributor.authorHelfand, Brian-
dc.contributor.authorMamawala, Mufaddal-
dc.contributor.authorWu, Yishuo-
dc.contributor.authorLandis, Patricia-
dc.contributor.authorYu, Hongjie-
dc.contributor.authorWiley, Kathleen-
dc.contributor.authorNa, Rong-
dc.contributor.authorShi, Zhuqing-
dc.contributor.authorPetkewicz, Jacqueline-
dc.contributor.authorShah, Sameep-
dc.contributor.authorFantus, Richard J.-
dc.contributor.authorNovakovic, Kristian-
dc.contributor.authorBrendler, Charles B.-
dc.contributor.authorZheng, S. Lilly-
dc.contributor.authorIsaacs, William B.-
dc.contributor.authorXu, Jianfeng-
dc.date.accessioned2022-07-20T12:03:44Z-
dc.date.available2022-07-20T12:03:44Z-
dc.date.issued2019-
dc.identifier.citationEuropean Urology, 2019, v. 75, n. 5, p. 743-749-
dc.identifier.issn0302-2838-
dc.identifier.urihttp://hdl.handle.net/10722/314354-
dc.description.abstractBackground: Mutations in DNA repair genes are associated with aggressive prostate cancer (PCa). Objective: To assess whether germline mutations are associated with grade reclassification (GR) in patients undergoing active surveillance (AS). Design, setting, and participants: Two independent cohorts of PCa patients undergoing AS; 882 and 329 patients from Johns Hopkins and North Shore, respectively. Outcome measurements and statistical analysis: Germline DNA was sequenced for DNA repair genes, including BRCA1/2 and ATM (three-gene panel). Pathogenicity of mutations was defined according to the American College of Medical Genetics guidelines. Association of mutation carrier status and GR was evaluated by a competing risk analysis. Results and limitations: Of 1211, 289 patients experienced GR; 11 of 26 with mutations in a three-gene panel and 278 of 1185 noncarriers; adjusted hazard ratio (HR) = 1.96 (95% confidence interval [CI] = 1.004–3.84, p = 0.04). Reclassification occurred in six of 11 carriers of BRCA2 mutations and 283 of 1200 noncarriers; adjusted HR = 2.74 (95% CI = 1.26–5.96, p = 0.01). The carrier rates of pathogenic mutations in the three-gene panel, and BRCA2 alone, were significantly higher in those reclassified (3.8% and 2.1%, respectively) than in those not reclassified (1.6% and 0.5%, respectively; p = 0.04 and 0.03, respectively). Carrier rates for BRCA2 were greater for those reclassified from Gleason score (GS) 3 + 3 at diagnosis to GS ≥4 + 3 (4.1% vs 0.7%, p = 0.01) versus GS 3 + 4 (2.1% vs 0.6%; p = 0.03). Results are limited by the small number of mutation carriers and an intermediate end point. Conclusions: Mutation status of BRCA1/2 and ATM is associated with GR among men undergoing AS. Patient summary: Men on active surveillance with inherited mutations in BRCA1/2 and ATM are more likely to harbor aggressive prostate cancer. Men with inherited mutations in DNA repair genes (BRCA1/2 and ATM) have a greater risk of grade reclassification on active surveillance (AS) than those without. Mutation status can help inform decisions for AS.-
dc.languageeng-
dc.relation.ispartofEuropean Urology-
dc.subjectActive surveillance-
dc.subjectATM-
dc.subjectBRCA1-
dc.subjectBRCA2-
dc.subjectGermline mutations-
dc.titleGermline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.eururo.2018.09.021-
dc.identifier.pmid30309687-
dc.identifier.pmcidPMC6699614-
dc.identifier.scopuseid_2-s2.0-85054452553-
dc.identifier.volume75-
dc.identifier.issue5-
dc.identifier.spage743-
dc.identifier.epage749-
dc.identifier.eissn1873-7560-
dc.identifier.isiWOS:000464019200016-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats