Exposure to Agent Orange Associated With Increased Prevalence of Thyroid Cancer in Veterans

According to a recent descriptive analysis of the Veterans Administration (VA) Corporate Data Warehouse, veterans who reported Agent Orange exposure had higher rates of thyroid cancer compared to the overall national VA health care patient population.

Lead investigator Karen T. Le, MD, an endocrine fellow at Cedars Sinai Medical Center and VA Greater Los Angeles Healthcare Center in Los Angeles, California, presented these findings on March 6, 2015, at The Endocrine Society’s 97th Annual Meeting in San Diego, California.

The incidence of thyroid cancer nearly tripled between 1975 and 2009 (from 4.9 to 14.3 per 100,000 people). Although improved methods of detection have contributed in part to this increase, Le and her colleagues hypothesize that the VA patient population may have additional risk factors, such as Agent Orange exposure, that may contribute in part to increased prevalence of thyroid cancer.

US soldiers used Agent Orange, a mixture of two herbicides (2,4,5-trichlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid) that was contaminated by the toxin 2,3,7,8-tetrachlorodibenzodioxin (TCDD) during manufacturing, to destroy foliage hiding North Vietnamese troops during the Vietnam War. According to Le, TCDD is a known carcinogen, and Agent Orange exposure has been associated with numerous forms of cancer, including Hodgkin’s disease, non-Hodgkin’s lymphoma, and soft tissue sarcomas.

However, the relationship between thyroid cancer and Agent Orange exposure in the veteran population has not been clarified. Le and her colleagues performed a descriptive analysis of the VA Corporate Data Warehouse database from all U.S. Veterans Health Administration (VHA) health care sites from October 1, 1999, to December 31, 2013.

She and her colleagues used the 193 diagnosis code from the The International Classification of Diseases, 9th Revision (ICD-9) to identify 19,592 veterans who had been diagnosed with thyroid cancer over the 14-year study period, of which 42% were Vietnam era veterans. Self-reported exposure to Agent Orange was significantly higher in patients with thyroid cancer (10.0%) than in those in the general VHA population (6.2%).

“We will need further studies to determine whether this is a cause-and-effect relationship between Agent Orange exposure and thyroid cancer,” said Le. “But we wanted [this study] to increase awareness of the possible correlation.”

The prevalence rate in veteran men (1:1023) was similar to that of the U.S. general population in 2011 (1:1219). The veteran women had a lower prevalence rate (1:1114) than their nonveteran counterparts in 2011 (1:350). However, Le noted that the small number of female veterans (14% of the total cohort) may have biased the results and limited the ability to draw conclusions.

“The VA [database] is a very male-dominated compilation of patients, so when it comes to any type of female correlation, we have to be very careful with our analyses,” said Le.

Although the relationship between Agent Orange exposure and thyroid cancer seems plausible, Le indicated that more studies in different populations are needed to confirm this association. For example, Le stated that she and her colleagues are investigating whether farm workers who work with herbicides have a higher incidence of thyroid cancer and whether the characteristics of those patients are similar to the ones in the VA database. However, she indicated that Agent Orange exposure is limited to Vietnam era veterans and farm workers who were accidentally exposed, which may limit the generalizability of the association.

According to Le, veterans may be eligible to receive special health care benefits and services if they suffer from conditions, such as non-Hodgkin’s lymphoma and certain respiratory cancers, linked to Agent Orange exposure during their military service. Although the results from this study alone would not be sufficient to establish such benefits for thyroid cancer, she hopes they increase awareness about the possible link between Agent Orange exposure and thyroid cancer.

Although the current study did not investigate the relative proportions of thyroid cancer types, which was partially due to the highly confidential nature of the VA database, Le stated that one of the next goals for her and her colleagues is to analyze different cohorts and the histological subtypes associated with Agent Orange exposure, as well as the overall survival trends and treatments among these subtypes.

“I think it will be really helpful to get that data to shine some more light on the [mechanism behind Agent Orange exposure and development of thyroid cancer],” said Le.

Le KT, Sawick MP, Want MB, et al. High Prevalence of Agent Orange Exposure Among Thyroid Cancer Patients in the National VA Healthcare System. Database. Presented at: The Endocrine Society’s 97th Annual Meeting (ENDO 2015); March 5-8, 2015; San Diego, CA. Abstract FRI-040.

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