Agent Orange Tied to Multiple Myeloma Precursor

Troy Brown, RN

September 03, 2015

Veterans who sprayed the herbicide Agent Orange during the Vietnam War were twice as likely to have monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, according to a prospective cohort study.

"To our knowledge, our findings provide the first direct scientific evidence for an association between the multiple myeloma precursor, MGUS, and Agent Orange/[2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] exposure among the Ranch Hand veterans," the researchers write.

Ola Landgren, MD, PhD, from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland, and Memorial Sloan Kettering Cancer Center, New York City, and colleagues present their findings in an article published online September 3 in JAMA Oncology.

"Although the cause of MGUS and multiple myeloma remains largely unclear, previous cohort and case control studies have reported an elevated risk of multiple myeloma among farmers and other agricultural workers," the researchers explain. "More specifically, pesticides (ie, insecticides, herbicides, fungicides) have been hypothesized as the basis for these associations."

The researchers analyzed blood specimens that were collected and stored in 2002 as part of the Air Force Health Study (AFHS). The researchers also analyzed relevant exposure data by the AFHS.

The study included 479 veterans who had conducted aerial spray missions of the herbicide Agent Orange as part of Operation Ranch Hand (Ranch Hand veterans).

The study also enrolled 479 comparison veterans who performed similar duties in Southeast Asia during 1962 to 1971 but did not participate in herbicide spray missions. All participants in the study underwent a follow-up examination for the AFHS in 2002. The researchers were blinded to the exposure data for each sample at the time of analysis, the authors note.

As part of the AFHS, serum TCDD levels were measured in 1987, 1992, 1997, and 2002.

Demographic and lifestyle characteristics and medical histories were similar for the Ranch Hand veterans and the comparison veterans.

The crude prevalence of overall MGUS was 7.1% (34 of 479) in veterans who sprayed herbicides and 3.1% (15 of 479) in comparison veterans. However, after adjusting for potential confounders including age, race, and body mass index in 2002, the Ranch Hand veterans were more likely to have MGUS (adjusted odds ratio [OR], 2.37; 95% confidence interval [CI], 1.27 - 4.44; P = .007).

The risk for MGUS was significantly higher in veterans younger than 70 years (OR, 3.4; 95% CI, 1.46 - 8.13; P = .004), but there was no significant increase in the risk in those aged 70 years or older (OR, 1.4; 95% CI, 0.55 - 3.63; P = .63).

"Our findings of increased MGUS risk among Ranch Hand veterans supports an association between Agent Orange exposure and multiple myeloma," the researchers conclude.

Dr Landgren reports scientific presentations at a meeting funded by Onyx Pharmaceuticals/AMGEN, Celgene, BMS, and Jansen, and has served on the Independent Data Monitoring Committee for clinical trials by Millennium Pharmaceuticals/Takeda. The other authors have disclosed no relevant financial relationships.

JAMA Oncol. Published online September 3, 2015. Full text

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