Genetic risk and likelihood of prostate cancer detection on first biopsy by ancestry

Author:

Lee Kyung Min1,Nelson Tyler J1,Bryant Alex23,Teerlink Craig C14,Gulati Roman5ORCID,Pagadala Meghana S678,Tcheandjieu Catherine91011,Pridgen Kathryn M14,DuVall Scott L14,Yamoah Kosj1213ORCID,Vassy Jason L141516,Seibert Tyler M6171819,Hauger Richard L62021,Rose Brent S617,Lynch Julie A14ORCID

Affiliation:

1. VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System , Salt Lake City, UT, USA

2. Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System , Ann Arbor, MI, USA

3. Department of Radiation Oncology, University of Michigan , Ann Arbor, MI, USA

4. Department of Internal Medicine, School of Medicine, University of Utah , Salt Lake City, UT, USA

5. Division of Public Health Sciences, Fred Hutchinson Cancer Center , Seattle, Washington, USA

6. VA San Diego Healthcare System , San Diego, CA, USA

7. Medical Scientist Training Program, University of California San Diego , La Jolla, CA, USA

8. Biomedical Science Program, University of California San Diego , La Jolla, CA, USA

9. VA Palo Alto Health Care System , Palo Alto, CA, USA

10. Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes , San Francisco, CA, USA

11. Department of Epidemiology and Biostatistics, University of California San Francisco , San Francisco, CA, USA

12. Department of Radiation Oncology, H. Lee Moffitt Cancer Center , Tampa, FL, USA

13. James A. Haley Veterans’ Hospital , Tampa, FL, USA

14. Section of General Internal Medicine, VA Boston Healthcare System , Boston, MA, USA

15. Department of Medicine, Harvard Medical School , Boston, MA, USA

16. Department of Medicine, Brigham and Women’s Hospital , Boston, MA, USA

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

18. Department of Radiology, University of California San Diego , La Jolla, CA, USA

19. Department of Bioengineering, University of California San Diego , La Jolla, CA, USA

20. Center for Behavior Genetics of Aging, University of California San Diego , La Jolla, CA, USA

21. Department of Psychiatry, University of California San Diego , La Jolla, CA, USA

Abstract

Abstract Despite differences in prostate cancer risk across ancestry groups, relative performance of prostate cancer genetic risks scores (GRS) for positive biopsy prediction in different ancestry groups is unknown. This cross-sectional retrospective analysis examines the association between a polygenic hazard score (PHS290) and risk of prostate cancer diagnosis upon first biopsy in male veterans using 2-sided tests. Our analysis included 36 717 veterans (10 297 of African ancestry). Unadjusted rates of positive first prostate biopsy increased with higher genetic risk (low risk: 34%, high risk: 58%; P < .001). Among men of African ancestry, higher genetic risk was associated with increased prostate cancer detection on first biopsy (odds ratio = 2.18, 95% confidence interval = 1.93 to 2.47), but the effect was stronger among men of European descent (odds ratio = 3.89, 95% confidence interval = 3.62 to 4.18). These findings suggest that incorporating genetic risk into prediction models could better personalize biopsy decisions, although further study is needed to achieve equitable genetic risk stratification among ancestry groups.

Funder

Million Veteran Program

Department of Veterans Affairs

Informatics and Computing Infrastructure

United States Government

National Institutes of Health

Department of Veteran Affairs

University of California San Diego

VISN-22 VA Center of Excellence for Stress and Mental Health

National Institute of Aging

Prostate Cancer Foundation Challenge

Publisher

Oxford University Press (OUP)

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Genomic risk scores in prostate cancer: polygenic yes, but are they poly-ancestral?;JNCI: Journal of the National Cancer Institute;2024-02-16

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