Associate Chief Medical Officer, UTMB Clear Lake; Medical Director for High Valu University of Texas Medical Branch
Introduction: To date, limited data exist regarding the link between Agent Orange (AO) and bladder cancer (BC) risk and the Institute of Medicine (IOM) concluded the interplay between AO exposure and BC outcomes is an area of needed research. We examined the relationship between AO exposure and BC risk in Vietnam Veterans. Methods: We performed a nationwide Veterans Affairs (VA) retrospective cohort study to determine BC risk according to AO exposure. A total of 19,323,708 Vietnam Veterans enrolled in the VA from 2000-2019 were identified. Due to limited numbers of female patients exposed to agent orange, the study was limited to males. AO exposed patients were matched on a 1:3 basis by age, gender, race, military branch, and year of service entry to non-AO exposed patients. Risk of BC was measured by incidence and aggressiveness by muscle-invasion status using natural language processing. Multivariable cox proportional-hazards regression was used to test the association between AO and BC incidence with time zero being entry into the VA system. Multivariable logistic regression was used to test the association between AO and BC aggressiveness among men with BC. Results: After inclusion and exclusion criteria, there were 629,907 (25.0%) patients with AO exposure and 1,888,019 (75.0%) matched patients without AO exposure. AO exposure was associated with significant increased risk of BC, though effect was very slight (Hazard ratio (HR) 1.03; 95% Confidence Interval (CI) 1.01-1.05). When stratified by median age at VA entry, AO was not associated with significant BC risk among older patients but was associated with increased BC risk among younger patients (HR 1.07; 95% CI 1.04-1.10). Among veterans diagnosed with BC (n=50,781), AO was associated with lower risk of muscle-invasive BC (Odds ratio (OR) 0.91, 95% CI, 0.85-0.98). Conclusions: In the largest case matched study among Vietnam Veterans to date, there was an increased risk of BC, but not BC aggressiveness among AO exposed Veterans, though the increased risk was small. These findings suggest a link between AO exposure and risk of BC. SOURCE OF Funding: This study was conducted with the support of a Department of Defense Peer Reviewed Cancer Research Program (PRCRP) Career Development Award (W81XWH1710576) (SBW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense or Veterans Affairs.
