Agent Orange Exposure Linked to Myeloma Precursor Risk


Vietnam War veterans exposed to Agent Orange as part of Operation Ranch Hand were at double the risk for monoclonal gammopathy of undetermined significance, a precursor to multiple myeloma, according to results of a new study.

Helicopter spraying agent orange during Vietnam War. Image © copyright Everett Historical /

Vietnam War veterans exposed to Agent Orange as part of Operation Ranch Hand were at double the risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, according to the results of a study published in JAMA Oncology.

“Our observations are important in that they add support to a previous finding that certain pesticides play a role in the development of MGUS,” wrote Ola Landgren, MD, PhD, of Memorial Sloan Kettering Cancer Center, and colleagues.

According to background information in the study, certain herbicides and pesticides have been hypothesized as the causes for increased rates of MGUS and multiple myeloma among farmers and agricultural workers.

In this study, the researchers examined stored serum samples from 958 United States Air Force veterans: 479 who conducted aerial herbicide spray missions of Agent Orange in Vietnam between 1962 and 1971 (Ranch Hand veterans) and 479 who did similar missions in Southeast Asia during that same period but were not involved in herbicide spray missions (controls). The study measured exposure to Agent Orange by measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the contaminant of Agent Orange, in serum samples in 1987, 1992, 1997, and 2002.

MGUS occurred in 7.1% of Ranch Hand veterans compared with 3.1% of comparison veterans. According to the researchers, after adjusting for age, race, body mass index (BMI) in 2002, and the change in BMI between 2002 and the time of TCDD measurement, there was a 2.4-fold increased risk for MGUS in veterans exposed to Agent Orange compared with veterans who were not (adjusted odds ratio [OR], 2.37 [95% confidence interval (CI), 1.27–4.44]; P = .007).

The study also showed that those veterans younger than 70 years had a significantly increased risk for MGUS (OR = 3.4 [95% CI, 1.46–8.13]; P = .004), whereas no significant risk for MGUS was seen in those 70 years or older.

The researchers acknowledged that one of the limitations of their study was that TCDD measurements were taken 25 years after exposure and the study could not account for whole-body elimination of TCDD.

“Furthermore, a higher proportion of Ranch Hand veterans (86.6%) had a TCDD level measured in 1987 than did comparison veterans (74.1%), which could have introduced a bias in our results,” they wrote.

In an editorial that accompanied the study, Nikhil C. Munshi, MD, of Dana-Farber Cancer Institute, wrote that this study provided further evidence of associations between plasma cell disorders and Agent Orange.

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

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