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Germline alterations among Hispanic men with prostate cancer

Prostate Cancer and Prostatic Diseases volume 25, pages 561–567 (2022)Cite this article

Subjects

A Correction to this article was published on 29 April 2022

This article has been updated

Abstract

Background

Little is known about the true rate of pathogenic (P)/likely pathogenic (LP) germline alterations in Hispanic men with prostate cancer as most studies analyzing the prevalence of P/LP germline alterations were performed in a largely non-Hispanic white population (NHW).

Methods

We performed a retrospective analysis of two separate cohorts of men with prostate cancer: (1) a multicenter cohort of 17,256 men who underwent germline testing in a CLIA-certified laboratory and (2) a single-center cohort of all men eligible for germline testing between 2018 and 2020. The proportions of P/LP alterations and variants of uncertain significance (VUS) were computed. Fisher’s exact test was used to compare germline alteration rates for significance. A multivariate logistic regression was performed adjusting for demographic and clinical factors to examine factors associated with germline testing.

Results

In the multicenter cohort, the rate of P/LP germline alterations among self-reported Hispanic men was 7.1%, which was lower than self-reported NHW men (9.7% vs. 7.1%, p = 0.058), but was not statistically significant. The VUS rate was significantly higher among the Hispanic cohort (21.5% vs. 16.6%, p = 0.005). In the single-center cohort, 136 Hispanic patients were eligible for testing of which 34 underwent germline testing (26.1%, N = 34/136). Of all prostate cancer patients in the single-center cohort undergoing germline testing (n = 173), the rate of P/LP alterations in Hispanic patients was not significantly different compared to NHW patients (14.7% vs. 12.2%, p = 0.77). The rate of VUS in Hispanic patients was significantly higher than that of NHW patients (20.6% vs. 7.2%, p = 0.047).

Conclusion

The P/LP germline alteration rate in our cohorts was similar between Hispanic and NHW men. The rate of VUS was significantly higher in Hispanic men, a consequence of undertesting in minority populations. These data support that Hispanic men with prostate cancer should be screened for germline testing similar to NHW men.

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Fig. 1: Distribution of prostate cancer-specific germline alterations in single-center and multi-center cohorts.
Fig. 2

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Data availability

Datasets on which the conclusions of this paper relay are available to readers promptly upon request.

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Acknowledgements

We thank Invitae for providing data.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA, USA

    Elizabeth Pan, Justin Shaya, Lisa Madlensky, J. Michael Randall, Frederick E. Millard, Nicole Weise, James Murphy, Maria Elena Martinez & Rana R. McKay

  2. Department of Urology, University of California San Diego, La Jolla, CA, USA

    Juan Javier-Desloges & J. Kellogg Parsons

  3. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA

    Brent Rose

  4. Invitae Corporation, San Francisco, CA, USA

    Sarah M. Nielsen, Kathryn E. Hatchell, Edward D. Esplin & Robert L. Nussbaum

Authors
  1. Elizabeth Pan
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  2. Justin Shaya
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  4. J. Michael Randall
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  5. Juan Javier-Desloges
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Contributions

RRM, JS, and EP contributed to the study concept and design. RRM, EP, and JS drafted the paper. All authors were involved in the acquisition, analysis, or interpretation of data, and participated in critical revision of the paper for important intellectual content and provided approval of the final paper. RRM supervised the study.

Corresponding author

Correspondence to Rana R. McKay.

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Competing interests

RRM received research funding from Bayer, Pfizer, Tempus; serves on Advisory Board for AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Exelixis, Janssen, Merck, Novartis, Pfizer, Sanofi, Tempus; is a consultant for Dendreon, Myovant, Sorrento Therapeutics, Vividion; serves on the molecular tumor board at Caris. RLN is a consultant and stockholder in Maze Therapeutics and Genome Medical and a consultant for Pfizer Pharmaceuticals. SMN, KEH, EDE, and RLN are employees and stockholders of Invitae.

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The original online version of this article was revised to add author Juan Javier-Desloges.

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Pan, E., Shaya, J., Madlensky, L. et al. Germline alterations among Hispanic men with prostate cancer. Prostate Cancer Prostatic Dis 25, 561–567 (2022). https://doi.org/10.1038/s41391-022-00517-6

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