Agent Orange exposure not among risk factors linked to liver cancer in Vietnam veterans
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Researchers found no association between Agent Orange exposure and hepatocellular carcinoma among Vietnam veterans, according to study results published in JAMA Network Open.
They instead discovered several risk factors linked to HCC among veterans, including viral hepatitis, nonalcoholic fatty liver disease, and alcohol and tobacco use.
“By identifying these factors early, we can potentially modify them and decrease the risk [for] developing not only liver cancer, but also cirrhosis,” Jihane N. Benhammou, MD, PhD, assistant clinical professor at UCLA’s David Geffen School of Medicine, told Healio. “The VA has done an amazing job at curing most veterans of hepatitis C,” she added. “Our focus is now shifting to chronic liver disease care, including identifying these modifiable risk factors early and screening for HCC.
Background
Patients with HCC have a 5-year survival rate of just 18%, per study background.
HCC has several risk factors — primarily cirrhosis — but others are not as defined.
Previous research on Agent Orange linked the herbicide with multiple cancers, including bladder cancer, Hodgkin and non-Hodgkin lymphoma, and prostate cancer, among others, but its association with HCC is unclear.
“My patients commonly ask me if Agent Orange has been shown to be associated with [HCC],” Benhammou said.
Animal testing connected 2,3,7,8-tetrachlorodibenzo-p-dioxin — a component of Agent Orange — with HCC, yet sample-size issues and other circumstances hindered further examination in veterans.
“We hypothesized that we would find a small, yet significant association between Agent Orange and HCC,” Benhammou said.
Methods
Investigators conducted an observational study of Vietnam veterans who served between 1966 and 1975.
The population consisted of men aged at least 18 years old when they deployed and had a follow-up visit at one of the 168 Veteran Affairs medical enters between 2000 and 2019.
Researchers used data collected from the disability database to separate veterans exposed to Agent Orange — defined as having a medical condition associated with the poison and having served where it was used — and those not exposed.
They also distinguished between veterans who had cirrhosis and those who did not because cirrhosis is the leading critical risk factor for HCC.
Results and what’s next
Of a population of 296,505 veterans (75.1% white, 15% Black), 2,654 had HCC, with an insignificant split of veterans exposed to Agent Orange (1,463) and those not exposed (1,191).
Similarly, the researchers’ data analysis could not connect Agent Orange with HCC in veterans with cirrhosis (adjusted HR = 1; 95% CI, 0.91-1.1) or without cirrhosis (adjusted HR, 1.05; 95% CI, 0.89-1.23).
However, Hispanic veterans with cirrhosis (adjusted HR = 1.51; 95% CI, 1.3-1.75) and Black veterans with cirrhosis (adjusted HR = 1.18; 95% CI, 1.05-1.32) had a significantly higher risk for HCC than white veterans. Additionally, patients with cirrhosis had several other risk factors for HCC, including viral hepatitis (adjusted HR = 3.71; 95% CI, 3.26-4.24), nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (adjusted HR = 1.92; 95% CI, 1.72-2.15), and alcoholic liver disease (adjusted HR = 1.32; 95% CI, 1.19-1.46).
Veterans had a risk factor of diabetes (adjusted HR = 1.50; 95% CI, 1.13-2.01), but only before cirrhosis.
“We interpreted these results to indicate that it is important to prevent and control diabetes before cirrhosis; however, once cirrhosis develops, [it] becomes the main driver for HCC,” Benhammou said.
More work needs to be done examining how modifying risk factors could alter veterans’ chances of developing HCC, he added.
“Most of our patients have more than one factor affecting their chance of developing HCC,” Benhammou said. “Many people are doing important work on developing HCC risk calculators, which can help inform who to screen. Moreover, these risks are likely dynamic, and more work will need to be done to understand how risks change over time.”
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