Agent Orange exposure raises MGUS risk

By Shreeya Nanda, Senior medwireNews Reporter

The risk of monoclonal gammopathy of undetermined significance (MGUS) is significantly higher in individuals exposed than those not exposed to Agent Orange, shows a study of US Air Force personnel.

MGUS is a precursor state of multiple myeloma, explain Ola Landgren (Memorial Sloan Kettering Cancer Center, New York, USA) and co-authors, and thus their findings support “an association between Agent Orange exposure and multiple myeloma”.

Among 479 male participants of the Air Force Health Study who carried out aerial herbicide spray missions of Agent Orange – termed Operation Ranch Hand – during the Vietnam War (1962–1971), the prevalence of MGUS in 2002 was 7.1%. This compared with a prevalence of 3.1% among 479 men who had similar responsibilities in Southeast Asia during the same time period but no involvement in herbicide spray missions.

After accounting for factors such as age, ethnicity and body mass index in 2002, this equated to a 2.37-fold increased risk of MGUS for Ranch Hand veterans compared with controls.

Moreover, the levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a contaminant believed to be responsible for most of Agent Orange’s toxicity, were significantly associated with cohort status, the researchers report. Specifically, Ranch Hand veterans compared with controls were significantly more likely to have TCDD levels that exceeded 10.92 parts per trillion (ppt) and significantly less likely to have TCDD levels of 3.65 ppt or below, at 47.5% versus 2.5% and 9.4% versus 40.9%, respectively.

MGUS risk rose with increasing body burden of TCDD, with unadjusted odds ratios of 2.09, 2.62 and 2.81 for TCDD levels of 3.66 to 5.80 ppt, 5.81 to 10.92 ppt and over 10.92 ppt, respectively, compared with TCDD levels of 3.65 ppt and below, although these associations did not reach statistical significance.

In an accompanying editorial in JAMA Oncology, Nikhil Munshi (Dana-Farber Cancer Institute, Boston, Massachusetts, USA), notes that the authors used 1987 as the reference point for TCDD levels, either using measurements taken that year or reconstructing based on predicted half-life from measurements at later time points.

This “brings a level of heterogeneity to the data” as there could be a gap of anywhere between 25 to 16 years between exposure to Agent Orange, between 1962 and 1971, and TCDD assessment, he says.

But the editorialist commends the authors on their use of well-characterised samples, long follow-up and availability of measurements of toxin exposure, and for bringing “clarity to the risk of [Agent Orange] exposure and plasma cell disorder”.

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