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Original Investigation
November 2015

Agent Orange Exposure and Monoclonal Gammopathy of Undetermined SignificanceAn Operation Ranch Hand Veteran Cohort Study

Author Affiliations
  • 1National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 2Memorial Sloan Kettering Cancer Center, New York, New York
  • 3Agency for Toxic Substances and Disease Registry, Atlanta, Georgia
  • 4Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio
  • 5Clinical Center, National Institutes of Health, Bethesda, Maryland
  • 6Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark
  • 7Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland
  • 8National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia
JAMA Oncol. 2015;1(8):1061-1068. doi:10.1001/jamaoncol.2015.2938

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.