Agent Orange exposure linked to increased risk for bladder cancer among Vietnam veterans
Click Here to Manage Email Alerts
Key takeaways:
- The modest association may have clinical relevance for the care of younger Vietnam veterans.
- Veterans exposed to Agent Orange had lower odds of developing muscle-invasive disease.
Men exposed to Agent Orange during their military service had a modestly increased risk for bladder cancer, results of a retrospective study of Vietnam veterans showed.
Despite the slightly higher risk among those exposed to the tactical herbicide, the analysis published in JAMA Network Open revealed no difference in bladder cancer aggressiveness among veterans diagnosed with the disease.
“This study was the largest retrospective cohort study to date from the largest equal access system in the U.S. and found a modest association between Agent Orange and bladder cancer risk,” Stephen B. Williams, MD, MBA, MS, the study’s lead author and director of urologic oncology at The University of Texas Medical Branch at Galveston, told Healio. “Bladder cancer has now been designated by the VA as an Agent Orange-associated disease.”
Background
A large proportion of bladder cancer cases cannot be attributed to known risk factors, according to study investigators.
Exposure to Agent Orange has come under increased scrutiny as a contributor to increased cancer risk, but little research into its impact in bladder cancer exists, they added.
“To provide a true measure of aggressive bladder cancer, it is crucial to study not just the diagnosis of bladder cancer but the aggressiveness of disease when diagnosed,” Williams and colleagues wrote. “However, to our knowledge, such a comprehensive analysis of Agent Orange and bladder cancer has not been done to date, mainly due to the small numbers of exposed cases, the lack of ability to identify Agent Orange exposure, and the lack of an ability to control for known confounders, particularly smoking, a major bladder cancer risk factor.”
Methodology
Williams and colleagues conducted a retrospective cohort study to identify any association between bladder cancer risk and exposure to Agent Orange among male Vietnam veterans.
The analysis used electronic heath records from male Vietnam veterans treated within the VA Health System from 2001 to 2019.
The study cohort comprised 2,517,926 men (median age at VA entry, 60 years), including 629,907 veterans exposed to Agent Orange and 1,888,019 unexposed veterans who served as control patients. Researchers matched patients exposed to Agent Orange in a 1:3 ratio to unexposed veterans based on age, race and ethnicity, military branch and year of service entry.
Researchers noted statistically significant but not clinically meaningful differences in baseline characteristics between the two study groups. They also reported fewer current smokers (20.9% vs. 23.7%; P < .001) and comorbidities (Charlson Comorbidity Index score of 3 or more: 17.3% vs. 18.7%; P < .001) among veterans exposed to Agent Orange compared with unexposed veterans.
Bladder cancer incidence — including the time to bladder cancer diagnosis — served as the study’s primary outcome measurement.
For the secondary outcome measurement, investigators used natural language processing to determine disease aggressiveness via muscle invasion status.
Key findings
With a follow-up of 28,672,655 person-years, researchers reported a total of 50,781 bladder cancer diagnoses. This included 2.1% of the study cohort exposed to Agent Orange compared with 2% among unexposed veterans.
Further analysis showed overall bladder cancer incidence of 1.77 cases per 1,000 person-years for the entire study cohort, 1.84 cases per 1,000 person-years for veterans exposed to Agent Orange and 1.75 cases per 1,000 person-years for unexposed veterans.
Researchers observed what they called a “very slight” but significantly increased risk for bladder cancer among Vietnam veterans exposed to Agent Orange (adjusted HR = 1.04; 95% CI, 1.02-1.06).
Veterans exposed to Agent Orange and younger than the median study cohort age had increased risk for bladder cancer compared with unexposed veterans (HR = 1.07; 95% CI, 1.04-1.1).
The researchers did not identify an association of Agent Orange exposure with bladder cancer risk among veterans older than the median study cohort age. However, they reported an association among veterans who entered military service between 1969 and 1975 (HR = 1.08; 95% CI, 1.04-1.12).
Among those diagnosed with bladder cancer, veterans exposed to Agent Orange had lower odds of developing muscle-invasive disease (OR = 0.91; 95% CI, 0.85-0.98).
Clinical implications
Despite suggesting only modestly higher bladder cancer risk among those exposed to Agent Orange, the results may have clinical relevance for the care of younger Vietnam veterans. These patients appear to be at greater risk, potentially because they have more life-years left during which they may develop bladder cancer, according to Williams and colleagues.
“This finding is critical because bladder cancer is more commonly diagnosed in older individuals, corresponding to the age of most Vietnam veterans who may have been exposed to Agent Orange,” they wrote. “Given that the VA has recently designated bladder cancer as a cancer caused by Agent Orange exposure, veterans who were exposed to Agent Orange during military service may be eligible for a variety of VA benefits, including disability compensation for diseases associated with Agent Orange exposure. Targeted screening could be implemented among people exposed to Agent Orange to detect bladder cancer earlier when it is more treatable.”
For more information:
Stephen B. Williams, MD, MBA, MS, can be reached at Division of Urology, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555; email: stbwilli@utmb.edu.
Collapse
Read more about
Click Here to Manage Email Alerts