26335650

PMC5701511

Importance

Multiple myeloma has been classified as exhibiting “limited or suggestive evidence” of an association with exposure to herbicides in Vietnam Veterans. Occupational studies have shown that other pesticides (i.e., insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma (MM) and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however no studies have uncovered such an association in Vietnam 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 Veterans.

Design

Our study is a prospective cohort study, 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 but were not involved in herbicide spray missions (comparison Veterans).

Setting

Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962–1971.

Participants

We included 479 Ranch Hand Veterans and 479 comparison Veterans who participated in the 2002 follow-up examination of AFHS.

Exposure

Agent Orange and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a contaminant of Agent Orange). Serum TCDD levels were measured in 1987, 1992, 1997, and 2002.

Main Outcomes and Measures

Risk of MGUS measured by prevalence, odds ratios (OR), and 95% confidence intervals (CI).

Results

The prevalence of MGUS in Ranch Hand Veterans (7.1%) was higher than in comparison Veterans (3.1%) (adjusted OR=2.37, 95% CI, 1.27–4.44; P=0.007). The cohort status was significantly (P=0.0001) associated with TCDD levels: 47% of Ranch Hand Veterans had serum TCDD levels >10.92 ppt compared to 2.5% of comparison Veterans.

Conclusions and Relevance

Ranch Hand Veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.

CDC Public Access

CC999999/Intramural CDC HHS/United States
Intramural NIH HHS/United States