Proteome-wide association study of prostate cancer risk across populations

Hua Zhong^#^{1

2}, Jingjing Zhu^#^{2

3}, Shuai Liu^{1

2}, Chong Wu⁴, Liang Wang⁵, Seamus P Whelton⁶, Catherine H Marshall⁷, Michael J Blaha⁸, Peter Durda⁹, Xiuqing Guo¹⁰, Craig W Johnson¹¹, Henry J Lin¹⁰, Kent D Taylor¹⁰, Russell P Tracy⁹, Ronit I Yarden¹², Ani W Manichaikul¹³, Stephen S Rich¹³, Jerome I Rotter¹⁰, Rajat Deo¹⁴, Ruth F Dubin¹⁵, Peter Ganz¹⁶, Lang Wu^{17

18}

Affiliations

¹ Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI, USA.
² Department of Interdisciplinary Oncology and Department of Genetics, LSU-LCMC Health Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
³ Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, HI, USA.
⁴ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Tumor Microenvironment and Metastasis, Moffitt Cancer Center, Tampa, FL, USA.
⁶ Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁷ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
⁹ Laboratory for Clinical Biochemistry Research, University of Vermont, Burlington, VT, USA.
¹⁰ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹¹ Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA, USA.
¹² Division of Cardiovascular Sciences, Epidemiology Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
¹³ Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
¹⁴ Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹⁵ Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁶ Division of Cardiology, Zuckerberg San Francisco General Hospital and Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI, USA. lwu3@lsuhsc.edu.
¹⁸ Department of Interdisciplinary Oncology and Department of Genetics, LSU-LCMC Health Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA. lwu3@lsuhsc.edu.

^# Contributed equally.

PMID: 41353205
DOI: 10.1038/s41467-025-66250-5

Free article

Proteome-wide association study of prostate cancer risk across populations

Hua Zhong et al. Nat Commun. 2025.

Free article

. 2025 Dec 6.

doi: 10.1038/s41467-025-66250-5. Online ahead of print.

Authors

Affiliations

¹ Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI, USA.
² Department of Interdisciplinary Oncology and Department of Genetics, LSU-LCMC Health Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
³ Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, HI, USA.
⁴ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Tumor Microenvironment and Metastasis, Moffitt Cancer Center, Tampa, FL, USA.
⁶ Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁷ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
⁹ Laboratory for Clinical Biochemistry Research, University of Vermont, Burlington, VT, USA.
¹⁰ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹¹ Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA, USA.
¹² Division of Cardiovascular Sciences, Epidemiology Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
¹³ Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
¹⁴ Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹⁵ Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁶ Division of Cardiology, Zuckerberg San Francisco General Hospital and Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI, USA. lwu3@lsuhsc.edu.
¹⁸ Department of Interdisciplinary Oncology and Department of Genetics, LSU-LCMC Health Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA. lwu3@lsuhsc.edu.

^# Contributed equally.

PMID: 41353205
DOI: 10.1038/s41467-025-66250-5

Abstract

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls of European population, 10,809 cases and 95,790 controls of Asian population, and 3931 cases and 26,405 controls of Hispanic/Latino population. We identify three, four, 15, and 73 PCa-associated proteins in African, Hispanic/Latino, Asian, and European populations, respectively, and 83 in trans-population meta-analysis. There are both pan-population and population-specific associations. Our findings provide valuable insights into etiology of PCa.

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Conflict of interest statement

Competing interests: Lang Wu provided consulting services to Pupil Bio Inc., Techspert, and Galiher DeRobertis & Waxman LLP, and reviewed manuscripts for Gastroenterology Report, not related to this study, and received honorarium. No potential conflicts of interest were disclosed by the other authors.

References

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Proteome-wide association study of prostate cancer risk across populations

Affiliations

Proteome-wide association study of prostate cancer risk across populations

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources