Agent orange exposure and prostate cancer risk in the million veteran program

Authors

  • Meghana S. Pagadala Research Service, VA San Diego Healthcare System, San Diego, CA, USA; Medical Scientist Training Program, University of California San Diego, La Jolla, CA, USA; Biomedical Science Program, University of California San Diego, La Jolla, CA, USA
  • Asona J. Lui Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
  • Allison Y. Zhong Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
  • Julie A. Lynch VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, UT, USA; Department of Internal Medicine, Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • Roshan Karunamuni Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
  • Kyung Min Lee VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, UT, USA; Department of Internal Medicine, Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • Anna Plym Division of Urology, Brigham and Women’s Hospital, Boston, MA, USA; Epidemiology, TH Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Brent S. Rose Research Service, VA San Diego Healthcare System, San Diego, CA, USA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
  • Hannah K. Carter Department of Medicine, University of California San Diego, La Jolla, CA, USA
  • Adam S. Kibel Division of Urology, Brigham and Women’s Hospital, Boston, MA, USA
  • Scott L. DuVall VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, UT, USA; Department of Internal Medicine, Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • J. Michael Gaziano Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA; Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
  • Matthew S. Panizzon Research Service, VA San Diego Healthcare System, San Diego, CA, USA; Center for Behavioral Genetics of Aging, University of California San Diego, La Jolla, CA, USA
  • Richard L. Hauger Research Service, VA San Diego Healthcare System, San Diego, CA, USA; Center for Behavioral Genetics of Aging, University of California San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, San Diego, CA, USA
  • Tyler M. Seibert Research Service, VA San Diego Healthcare System, San Diego, CA, USA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA; Department of Radiology, University of California San Diego, La Jolla, CA, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

DOI:

https://doi.org/10.2340/1651-226X.2024.25053

Keywords:

Agent Orange, prostate cancer, MVP, race/ethnicity, health disparities

Abstract

Background: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk.

Patients and Methods: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models.

Results and Interpretation: On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00–1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91–1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79–1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04–1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98–1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83–1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.

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Published

2024-05-23

How to Cite

Pagadala, M. S., Lui, A. J., Zhong, A. Y., Lynch, J. A., Karunamuni, R., Lee, K. M., Plym, A., Rose, B. S., Carter, H. K., Kibel, A. S., DuVall, S. L., Gaziano, J. M., Panizzon, M. S., Hauger, R. L., & Seibert, T. M. (2024). Agent orange exposure and prostate cancer risk in the million veteran program. Acta Oncologica, 63(1), 373–378. https://doi.org/10.2340/1651-226X.2024.25053

Issue

Vol. 63 (2024): Acta Oncologica

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Short report

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Copyright (c) 2023 Meghana S. Pagadala, Asona J. Lui, Allison Y. Zhong, Julie A. Lynch, Roshan Karunamuni, Kyung Min Lee, Anna Plym, Brent S. Rose, Hannah K. Carter, Adam S. Kibel, Scott L. DuVall, J. Michael Gaziano, Matthew S. Panizzon, Richard L. Hauger, Tyler M. Seibert

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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