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. 2017 May 4:1:PO.16.00039.
doi: 10.1200/PO.16.00039. eCollection 2017 May.

Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic Evaluation

Veda N Giri  1 , Elias Obeid  1 , Laura Gross  1 , Lisa Bealin  1 , Colette Hyatt  1 , Sarah E Hegarty  1 , Susan Montgomery  1 , Andrea Forman  1 , Ruth Bingler  1 , William K Kelly  1 , Adam P Dicker  1 , Stephanie Winheld  1 , Edouard J Trabulsi  1 , David Y T Chen  1 , Costas D Lallas  1 , Brian A Allen  1 , Mary B Daly  1 , Leonard G Gomella  1
Affiliations

Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic Evaluation

Veda N Giri et al. JCO Precis Oncol. .

Abstract

Purpose: Multigene panels are commercially available for the evaluation of prostate cancer (PCA) predisposition, which necessitates tailored genetic counseling (GC) for men. Here we describe emerging results of Genetic Evaluation of Men, prospective multigene testing study in PCA to inform personalized genetic counseling, with emerging implications for referrals, cancer screening, and precision therapy.

Patients and methods: Eligibility criteria for men affected by or at high risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Detailed demographic, clinical, and FH data were obtained from participants and medical records. Multigene testing was conducted after GC. Mutation rates were summarized by eligibility criteria and compared across FH data. The 95% CI of mutation prevalence was constructed by using Poisson distribution.

Results: Of 200 men enrolled, 62.5% had PCA. Eleven (5.5%; 95% CI, 3.0% to 9.9%) had mutations; 63.6% of mutations were in DNA repair genes. FH of breast cancer was significantly associated with mutation status (P = .004), and FH that met criteria for hereditary breast and ovarian cancer syndrome was significantly associated with PCA (odds ratio, 2.33; 95% CI, 1.05 to 5.18). Variants of uncertain significance were reported in 70 men (35.0%). Among mutation carriers, 45.5% had personal/FH concordant with the gene. A tailored GC model was developed based on emerging findings.

Conclusion: Multigene testing for PCA identifies mutations mostly in DNA repair genes, with implications for precision therapy. The study highlights the importance of comprehensive genetic evaluation for PCA beyond metastatic disease, including early-stage disease with strong FH. Detailed FH is important for referrals of men for genetic evaluation. The results inform precision GC and cancer screening for men and their male and female blood relatives.

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Conflict of interest statement

Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic EvaluationThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or po.ascopubs.org/site/ifc.Veda N. GiriStock and Other Ownership Interests: Novopyxis (I)Elias ObeidConsulting or Advisory Role: Merck Sharp & Dohme Research Funding: Merck, Myriad Genetics, GenentechLaura GrossNo relationship to discloseLisa BealinNo relationship to discloseColette HyattNo relationship to discloseSarah E. HegartyNo relationship to discloseSusan MontgomeryNo relationship to discloseAndrea FormanConsulting or Advisory Role: Invitae Speakers’ Bureau: InvitaeRuth BinglerNo relationship to discloseWilliam K. KellyNo relationship to discloseAdam P. DickerConsulting or Advisory Role: Glenview Consulting, Agios, EMD SeronoStephanie WinheldNo relationship to discloseEdouard J. TrabulsiConsulting or Advisory Role: GenomeDxDavid Y.T. ChenEmployment: Tenet Healthcare (I) Stock and Other Ownership Interests: Pfizer (I) Consulting or Advisory Role: Argos Therapeutics Travel, Accommodations, Expenses: Argos TherapeuticsCostas D. LallasNo relationship to discloseBrian A. AllenEmployment: Myriad Genetics Stock and Other Ownership Interests: Myriad GeneticsMary B. DalyNo relationship to discloseLeonard G. GomellaPatents, Royalties, Other Intellectual Property: NuView (Inst), NuView Travel, Accommodations, Expenses: AbbVie, Bayer AG, Astellas Pharma, Janssen Pharmaceuticals

Figures

Fig 1.
Fig 1.
Genetic Evaluation of Men (GEM) study flow diagram. GU, genitourinary.
See this image and copyright information in PMC

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