Agent Orange Exposure Is Associated With Esophageal Adenocarcinoma in Vietnam Veterans

Abstract

Introduction: Subjects exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the 1960's have been shown to have a higher incidence and severity of prostate cancer than the general population. TCDD is present in Agent Orange (AO), a herbicide sprayed in Vietnam from 1962-1971 exposing Vietnam Veterans. We investigated to see if it may play a role in development of esophageal adenocarcinoma (EAC). It has been associated with foregut intestinal cell metaplasia and promoting genetic instability in animal models. The goal was to determine if Vietnam era Veterans with a history of Agent Orange exposure exhibit an increased incidence of EAC compared to controls with nondysplastic Barrett's Esophagus (BE). Methods: Retrospective chart review of patients seen between 1/1/2001 and 12/31/2014 at the Carl T Hayden VA Medical Center. Vietnam era veterans males born between 1/1/1935 and 12/31/1952 with and without a history of TCDD exposure in the form of AO were studied in a case control format. 370 randomly selected controls with BE with no dysplasia seen on biopsy were compared to 158 patients diagnosed with EAC during the stated time period. Variables that were examined included a history of AO exposure as measured by being approved for inclusion in the AO Registry, age, smoking, and body mass index (BMI). Propensity scores (predictors of inclusion in the AO Registry) were calculated, and used in an adjusted logistic regression. Results: Patients in the AO Registry were 2.49 times as likely to develop EAC as compared to controls with nondysplastic BE who were not in the registry, on simple logistic regression, p < 0.0001. When adjusted for propensity score (based on age and BMI), the Odds Ratio for developing EAC was found to be 2.02 (p=0.003). Conclusion: There is a significant association between patients who are enrolled in the AO Registry from their service in Vietnam, and the development of EAC. This association holds when adjusted for propensity score. The pathway of progression from BE to adenocarcinoma is not fully understood. This exposed population may exhibit a more rapid progression of dysplasia from BE to EAC. If an association can be identified, increased screening in these individuals might be indicated.