In the Journals

Risk of MGUS, multiple myeloma greater in Vietnam veterans exposed to Agent Orange

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October 2, 2015

Vietnam veterans who were exposed to Agent Orange appear to have an increased risk for developing monoclonal gammopathy of undetermined significance, a precursor to multiple myeloma, according to results of a prospective study.

Researchers evaluated stored blood samples from U.S. Air Force personnel and found those who conducted Vietnam War missions that involved ‘Agent Orange’ herbicide had a more than twofold greater risk for developing monoclonal gammopathy of undetermined significance (MGUS).

Ola Landgren

Ola Landgren

Multiple myeloma has been classified as exhibiting ‘limited or suggestive evidence’ of an association with herbicides in Vietnam War veterans,” Ola Landgren, MD, PhD, chief of myeloma service at Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote. “Occupational studies have shown that other pesticides (insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state MGUS; however, to our knowledge, no [previous] studies have uncovered such an association in Vietnam War veterans.”

Landgren and colleagues conducted this prospective cohort study to determine the prevalence of MGUS among Operation Ranch Hand veterans compared to a control population and to assess the risk of MGUS in relation to the Agent Orange contaminant and human carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Operation Ranch Hand was part of a U.S. military strategy from 1962 to 1971 that involved spraying approximately 20 million gallons of herbicides over rural areas of South Vietnam in an attempt to deprive the Viet Cong of food and vegetation cover.

Researchers evaluated data from the Air Force Health Study, which collected and stored serum samples and relevant exposure data. A follow-up examination of the Air Force Health Study was performed in 2002.

Landgren and colleagues tested all of the specimens in 2013 without knowledge of the exposure status. Their analysis included data from 958 male veterans, 479 of whom were part of Operation Ranch Hand and 479 comparison veterans who did not fly on those missions. All cases and controls had similar demographics, medical histories and lifestyle characteristics.

The prevalence of MGUS was 7.1% in Ranch Hand veterans compared with 3.1% in the control group. This equated to a 2.4-fold increased risk for MGUS in the Ranch Hand veterans after adjusting for age, race, BMI and the time of blood draw for TCDD measurement in 2002 compared to the control cohort (adjusted OR = 2.37; 95% CI, 1.27-4.44).

Further, the risk for MGUS was significantly greater among veterans aged younger than 70 years (OR = 3.4; 95% CI, 1.46-8.13).

The researchers acknowledged several study limitations. There were no objective measurements of exposure to phenoxy herbicides, so researchers used cohort status as a surrogate. Also, the first TCDD measures weren’t taken until 1987 and — with 25 years between exposure and measurement — the researchers could not account for individual variations in the whole-body elimination of TCDD.

A bias may also have been introduced because a greater proportion of Ranch Hand veterans had a TCDD level measured in 1987 than controls (86.6% vs. 74.1%).

“Our observations are important in that they add support to a previous finding that certain pesticides play a role in the development of MGUS,” the researchers wrote. “In our study, the odds of having MGUS increased with increasing body burden of TCDD, although the trend was not statistically significant.”

These data provide strong evidence of an association between Agent Orange exposure and the development of plasma cell disorder, Nikhil C. Munshi, MD, director of basic and correlative science and senior physician at the Jerome Lipper Multiple Myeloma Center of Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, wrote in an accompanying editorial.

“[This] study … has brought clarity to the risk of Agent Orange exposure and plasma cell disorder,” Munshi wrote. “It also highlights the importance of tissue banking that allows investigation of a number of unanswered questions using modern methods.

“The emphasis now is to store samples from almost every major study with correlative science in mind, and this is essential if we are to understand disease biology, mechanism of response and resistance to therapy in the era of targeted therapy and precision medicine.” – by Anthony SanFilippo

Disclosure: Landgren reports a consultant/advisory role with Medscape Educations and other financial relationships with Amgen/Onyx, Bristol-Myers Squibb, Celgene, Janssen and Millennium/Takeda. Munshi and the other researchers report no relevant financial disclosures.

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