Differences in prostate cancer genomes by self-reported race: Contributions of genetic ancestry, modifiable cancer risk factors, and clinical factors Journal Article


Authors: Stopsack, K. H.; Nandakumar, S.; Arora, K.; Nguyen, B.; Vasselman, S. E.; Nweji, B.; McBride, S. M.; Morris, M. J.; Rathkopf, D. E.; Slovin, S. F.; Danila, D. C.; Autio, K. A.; Scher, H. I.; Mucci, L. A.; Solit, D. B.; Gönen, M.; Chen, Y.; Berger, M. F.; Schultz, N.; Abida, W.; Kantoff, P. W.
Article Title: Differences in prostate cancer genomes by self-reported race: Contributions of genetic ancestry, modifiable cancer risk factors, and clinical factors
Abstract: Purpose: Black men die from prostate cancer twice as often as White men, a disparity likely due to inherited genetics, modifiable cancer risk factors, and healthcare access. It is incompletely understood how and why tumor genomes differ by self-reported race and genetic ancestry. Experimental Design: Among 2,069 men with prostate cancer (1,841 self-reported White, 63 Asian, 165 Black) with access to clinical-grade sequencing at the same cancer center, prevalence of tumor and germline alterations was assessed in cancer driver genes reported to have different alteration prevalence by race. Results: Clinical characteristics such as prostate-specific antigen and age at diagnosis as well as cancer stage at sample procurement differed by self-reported race. However, most genomic differences persisted when adjusting for clinical characteristics. Tumors from Black men harbored fewer PTEN mutations and more AR alterations than those from White men. Tumors from Asian men had more FOXA1 mutations and more ZFHX3 alterations than White men. Despite fewer TP53 mutations, tumors from Black men had more aneuploidy, particularly chromosome arm 8q gains, an adverse prognostic factor. Genetic ancestry was associated with similar tumor alterations as self-reported race, but also with modifiable cancer risk factors. Community-level average income was associated with chr8q gains after adjusting for race and ancestry. Conclusions: Tumor genomics differed by race even after accounting for clinical characteristics. Equalizing access to care may not fully eliminate such differences. Therapies for alterations more common in racial minorities are needed. Tumor genomic differences should not be assumed to be entirely due to germline genetics. © 2021 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 28
Issue: 2
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2022-01-15
Start Page: 318
End Page: 326
Language: English
DOI: 10.1158/1078-0432.Ccr-21-2577
PUBMED: 34667026
PROVIDER: scopus
PMCID: PMC8776579
DOI/URL:
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
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MSK Authors
  1. Susan Slovin
    254 Slovin
  2. Michael Morris
    586 Morris
  3. David Solit
    782 Solit
  4. Mithat Gonen
    1034 Gonen
  5. Yu Chen
    134 Chen
  6. Karen Anne Autio
    120 Autio
  7. Dana Elizabeth Rathkopf
    275 Rathkopf
  8. Michael Forman Berger
    771 Berger
  9. Howard Scher
    1131 Scher
  10. Daniel C Danila
    155 Danila
  11. Wassim Abida
    158 Abida
  12. Nikolaus D Schultz
    491 Schultz
  13. Sean Matthew McBride
    301 McBride
  14. Philip Wayne Kantoff
    198 Kantoff
  15. Bastien Nguyen
    31 Nguyen
  16. Kanika Suresh Arora
    27 Arora
  17. Barbara Nweji
    5 Nweji