Malignant Changes in Bladder Cancer Associated with Defoliant Exposure
Abstract
This research project addresses the US Department of Defense (DoD) Fiscal Year 2019 (FY19) Peer Reviewed Cancer Research Program (PRCRP) Military Topic Area of bladder cancer and the Military Relevance Focus Area of militarily relevant risk factors associated with cancer (e.g., ionizing radiation, chemicals, infectious agents, and environmental carcinogens). The objective for the proposed project is to evaluate and confirm that the cancer-causing agents found in the defoliants used in Southeast Asian conflicts, Agent Orange (AO) and Agent Blue (AB), cause unique changes in bladder, which contribute to the development of bladder cancer (BCa). The rationale for this study includes the following; During the Vietnam conflict the United States military sprayed more than 20 million gallons of herbicides over the area of South Vietnam. AO contained the contaminant dioxin, which is among the most potent cancer-causing agents in mice. The lesser recognized defoliant AB contained arsenical compounds, which are an established cause of BCa. A large study of Korean Veterans demonstrated a significantly increased risk of being diagnosed with BCa as well as suffering from the consequences of having this disease in those with known exposure to these agents. As such, the DoD recently recognized a relationship between AO exposure and BCa. Despite these findings, AO’s ability to cause tumors in humans is poorly understood, and arsenic risk is based largely on population studies exploring association with exposure. In both cases, the possible mechanisms by which these agents lead to the development of BCa remains unknown. Successful completion of this proposal will likely result in identification of unique alterations in BCa related to defoliant exposure as that seen in Southeast Asia conflicts. This could lead to development of novel biomarkers related to clinical outcomes in this population and/or targetable pathways for novel therapeutics. As Veterans of this era are now approaching the age where BCa most commonly presents, further insight into the possible mechanisms contributing to their disease due to risks of exposure sustained during service is warranted. This project addresses the FY19 PRCRP Military Relevance Focus Area of militarily relevant risk factors associated with cancer (e.g., ionizing radiation, chemicals, infectious agents, environmental carcinogens, and stress). This is highly relevant to active duty Service members, Veterans, and other military beneficiaries in that defining a causal relationship with the development of BCa may increase the recognition of an association leading to more appropriate resources being put into care of those who served in this time.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010876
Entities
People
- John Taylor
Organizations
- United States Army
- University of Kansas Medical Center