Largest Agent Orange Study Shows Increased Prostate Cancer Risk

Orlando, Florida — Vietnam veterans who were exposed to the defoliate Agent Orange are 49% more likely than nonexposed veterans to be diagnosed with prostate cancer. That’s according to results from one of the largest studies to date examining that association.

The study was presented here at the 2011 Genitourinary Cancers Symposium, and adds to a mounting body of evidence implicating the defoliate in the development of prostate cancer.

“Even when numerous other risk factors were accounted for, exposure to Agent Orange increased risk significantly,” principal author Nathan Ansbaugh, MPH, told Medscape Medical News in an interview. “In our study it carried just as much risk as positive family history and even more risk than age,” he said.

Mr. Ansbaugh, along with colleagues from the Oregon Health and Science University, in Portland, conducted the retrospective study in association with the Portland VA Hospital.

Prime Time for Diagnosis

“This is an especially important finding,” Mr. Ansbaugh explained, “because . . . Vietnam veterans are reaching the age when we would consider them at highest risk of developing prostate cancer.” He said clinicians would do well to keep the association in mind when screening Vietnam veterans for prostate cancer.

The researchers used clinical data from 2720 veterans referred to the Portland VA Hospital for prostate biopsy between 1993 and 2010. In addition to checking for Agent Orange exposure, they evaluated several covariates, including prostate-specific antigen density, results of digital rectal exams, age at biopsy, family history, body mass index, race, and medication use. Then, using multiple logistic regression, they compared risk factors for men found to have prostate cancer with those for men whose biopsies were negative.

Mr. Ansbaugh and his group report that 896 men (32.9%) were found to have prostate cancer. After adjustment for all significant confounders, the researchers reported that veterans with prostate cancer were 49% more likely to have been exposed to Agent Orange than men who didn’t have cancer (odds ratio, 1.49; 95% confidence interval [CI], 1.06 to 2.11; P = .022).

Mr. Ansbaugh acknowledged that it’s difficult to quantify previous exposure to Agent Orange — which contained the known carcinogen dioxin — because it’s essentially based on patient reporting. “How much Agent Orange was used in the area where they were? How long were they there? Those are important questions, but difficult questions to answer,” he said.

“The result is that you end up having individuals who say they were exposed who may have not been. Or maybe they were, but they didn’t have significant exposure levels. Or you have individuals who are kind of cluttering that nonexposed group who didn’t say they had exposure or didn’t really know,” he said. “It’s one of the inherent limitations of the study.”

In previous years, numerous studies have been carried out looking at Agent Orange and prostate cancer. Although the results have consistently pointed to Agent Orange as a risk factor, the significance of findings has varied. “It’s only been in the past few years that we’ve seen such a strong association. We think that’s because Vietnam veterans are now into their 60s – the time when prostate cancer is often diagnosed,” Mr. Ansbaugh said.

Younger Age at Diagnosis

Exposure to Agent Orange was also associated with younger age at diagnosis. Men found to have prostate cancer were roughly 5 years younger at diagnosis than men without exposure. The average age at diagnosis for men exposed to the defoliate was 61.4 years (95% CI, 60.0 to 61.2), compared with 66.1 years (95% CI, 65.6 to 66.6) in unexposed men. “While that interaction between Agent Orange exposure and age wasn’t found to be significant in the multivariate model, our finding is similar to another study 3 years ago [Cancer. 2008;113:2464-2470], and warrants further attention,” Mr. Ansbaugh said.

Why is Agent Orange associated with the development of prostate cancer? “It’s not at all clear,” said Mr. Ansbaugh, “since many men were exposed and haven’t developed prostate cancer. We think there are probably some host factors at work here. It could be that exposure to Agent Orange functions as more of a promoter, a trigger mechanism for prostate cancer.”

Limitations of Retrospective Studies

Commenting on the study, Mike Scott, cofounder of Prostate Cancer International, a Web service that provides online science-based patient services, said the findings add to the increasing evidence of an association between the defoliate and prostate cancer. But like Mr. Ansbaugh, he acknowledged the limitations of the study. “The trouble is, when you come down to the individual patient level, there’s really no way to show positive proof of an association. You can’t collect prospective data because you don’t have the evidence before you,” he said.

“It’s similar to higher levels of myeloma that we’re seeing in people who were exposed to debris in the World Trade Center. We can’t correlate their illness to anything specific, so very likely there are host factors that figure into the development of the disease.”

He added that “with ever more information becoming available on the human genome, I wouldn’t be surprised if we find out that there are certain genetic traits or genetic translocations that are necessary to interact with Agent Orange and trigger the development of prostate cancer.”