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Cited by 75Pesticide Exposure and ToxicityMultiple Myeloma Research and TreatmentsOccupational Health and Performance

Agent Orange Exposure and Monoclonal Gammopathy of Undetermined Significance: An Operation Ranch Hand Veteran Cohort Study

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Landgren, Ola, Shim, Youn K., Michalek, Joel, Costello, Rene, Burton, Debra, Ketchum, Norma, Calvo, Katherine R., Caporaso, Neil +4 more·2015·JAMA Oncology
DOI 10.1001/jamaoncol.2015.2938PMC PMC5701511
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Abstract

IMPORTANCE: Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans. OBJECTIVE: To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS. EXPOSURES: Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. MAIN OUTCOMES AND MEASURES: Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs. RESULTS: The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P=.007). CONCLUSIONS AND RELEVANCE: Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.

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  • Patients exposed to certain agents (Agent Orange, pesticides, 9/11 World Trade Center dust) or suffering from specific conditions (HIV or Gaucher) have a higher prevalence of clonal populations.

    “Importantly, it has also been demonstrated that patients exposed to certain agents (e.g. Agent Orange in Vietnam veterans, pesticides in agricultural worker, or 9/11 World Trade Center dust in first responders) or those suffering from specific conditions (such as HIV or Gaucher) have a higher prevalence of these clonal populations. 37-39 40,41 42”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [38]

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Research works printed but not linked: 2

  1. [33]International Agency for Research on Cancer Chemical agents and related occupations. Vol 100F. A review of human carcinogens WHO Press Geneva, Switzerland 2012
  2. [45]Institute of Medicine Veterans and Agent Orange: Update 2012 National Academy Press Washington, DC 2013 24716252

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Authors
Landgren, O., Shim, Y. K., Michalek, J., Costello, R., Burton, D., Ketchum, N., Calvo, K. R., Caporaso, N., Raveche, E., Middleton, D., Marti, G., & Vogt, R. F.
Affiliations
  • National Institutes of Health (US)
  • Agency for Toxic Substances and Disease Registry (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • Rutgers New Jersey Medical School (US)
  • United States Food and Drug Administration (US)
  • Centers for Disease Control and Prevention (US)
Corresponding author
Landgren, Ola
ORCID
Venue
JAMA Oncology
Publisher
American Medical Association (AMA)
Published
2015-11-01
Volume
1
Issue
8
Pages
1061
ISSN
2374-2437 (ISSN-L)
DOI
10.1001/jamaoncol.2015.2938
PMC
PMC5701511
OpenAlex
W1828727770
Cited by
75
References
46
Citations by year
2026: 7 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 5 · 2016: 7
FWCI
8.47
Type
journal article
Language
en
Open access
Locations
  • JAMA Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (CC999999)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Health Professions › Occupational Therapy › Occupational Health and Performance
Keywords
Agent Orange, 2,3,7,8-tetrachlorodibenzo-p-dioxin, monoclonal gammopathy of undetermined significance, multiple myeloma, herbicide exposure, Vietnam War veterans, Operation Ranch Hand, occupational exposure, dioxin contamination, cancer risk
MeSH terms
Polychlorinated Dibenzodioxins, Agent Orange, Aged, Aged, 80 and over, Herbicides, Humans, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Prospective Studies, Risk Factors, Time Factors, United States, 2,4-Dichlorophenoxyacetic Acid, 2,4,5-Trichlorophenoxyacetic Acid, Biomarkers, Prevalence, Logistic Models, Odds Ratio, Case-Control Studies, Occupational Exposure, Risk Assessment, Vietnam Conflict, Veterans Health

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