Servicemembers exposed to Agent Orange during the Vietnam War are at higher risk of developing the precursor stage of a bone marrow cancer, according to a study published Thursday in the Journal of the American Medical Association Oncology.
The study provides the first scientific evidence for a link between the precursor stage of multiple myeloma -- a cancer of white blood plasma cells that accumulate in bone marrow -- and veterans exposed to the herbicide Agent Orange, according to the study's 12 authors, who are associated with medical centers across the U.S. The precursor, called monoclonal gammopathy of undetermined significance, or MGUS, is not in and of itself a problem.
"MGUS is not a cancer," said Dr. Nikhil Munshi, who specializes in multiple myeloma at the Dana-Farber Cancer Institute at Harvard Medical School in Boston. "A very large majority of patients with MGUS remain MGUS all through their lives with no real consequence."
MGUS virtually always precedes multiple myeloma, but the mechanisms that trigger its onset are not fully understood, said Munshi, who was not involved in the study but wrote an editorial published in the same issue of JAMA Oncology.
Previous studies have linked other insecticides, herbicides and fungicides to higher risks of MGUS and multiple myeloma.
Agent Orange was used during Operation Ranch Hand in Southeast Asia to clear jungle foliage from 1962 to 1971. It was usually sprayed via aircraft. Since then, Agent Orange has been linked to a host of health problems and diseases in many servicemembers.
The Veterans Administration maintains a list of "presumptive diseases" assumed to be related to military service that automatically qualify them for VA benefits. The Institute of Medicine has identified seven cancers with a positive association to Agent Orange, including chronic lymphocytic leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma -- all of which have been accepted by the VA as presumptive diseases.
Multiple myeloma is a VA presumptive disease, but it has been classified as having "limited or suggestive evidence" of a link to Vietnam War veterans' exposure to herbicides, the authors of the JAMA study wrote.
The study looked at specimens from two groups of Air Force veterans that had been collected and stored in 2002 by the Air Force Health Study. A group of 479 veterans who had been exposed to Agent Orange during Operation Ranch Hand were compared with a second group of the same size that had similar duties in Southeast Asia from 1962 to 1971 but were not involved with the herbicide.
The Air Force Health Study had sampled servicemembers in the two groups in 1987, 1992, 1997 and 2002 for exposure to Agent Orange and to 2,3,7,8-Tetrachlorodibenzo-p-dioxin, or TCDD, which is an unintended contaminant of the herbicide considered the culprit for so many of its adverse effects.
The researchers found that the prevalence of MGUS in Ranch Hand veterans was twice as high as in the comparison group, with 34 of the 479 Ranch Hand veterans having MGUS compared with 15 out of 479 in the control group.
That translated to a 2.4-fold increased risk of MGUS for Ranch Hand veterans over their counterparts when adjusting for factors such as age, race and other physical traits. "That's an important number," Munshi said. Researchers also found significantly higher levels of TCDD in the Ranch Hand veterans who had developed MGUS, he said.
Because all cases of multiple myeloma originate from MGUS, the study has provided the first scientific evidence for a direct link between Agent Orange and multiple myeloma, he said.