PORTLAND, OR—Vietnam-era veterans exposed to Agent Orange are almost 50% more likely to develop prostate cancer than unexposed veterans, making exposure to the defoliate a higher risk factor than age and on par with family history for veterans, according to recent research.
Furthermore, diagnosis of men who develop prostate cancer after exposure to Agent Orange occurs five years earlier, on average, than for those who have not experienced exposure, researchers reported earlier this year at the 2011 Genitourinary Cancers Symposium in Orlando, FL.
“We found exposure to Agent Orange increased risk more than age, which raises a man’s risk 32 percent after age 70. Exposure increases risk by nearly 50 percent, almost an identical rate to family history,” said Nathan Ansbaugh, MPH, principal author of the study.
“This is particularly important for physicians, as they may want to pay closer attention to whether a veteran has been exposed to Agent Orange when screening for prostate cancer,” noted Ansbaugh. Some 10,000 veterans are diagnosed with prostate cancer each year, according to VA.
Age and family history are the most significant risk factors for prostate cancer in the general population. Typically, men more than 50 years of age, African Americans, or those who have a first-degree relative such as a father, brother or son with prostate cancer are screened most aggressively because of their increased risk.
Ansbaugh and colleagues from the Oregon Health and Science University in Portland reviewed clinical data for 2,720 veterans. All patients had been referred to the Portland VAMC for prostate biopsies between 1993 and 2010. About one-third (896) of those referred were diagnosed with prostate cancer.
After adjusting for all major confounders, the research showed that those who had developed prostate cancer were 49% more likely to have experienced Agent Orange exposure than those who had negative biopsies (odds ratio, 1.49; 95% confidence interval [CI], 1.06 to 2.11; P = .022).
Researchers also evaluated a number of other covariates, including prostate-specific antigen density (PSA), age, family history, results of digital rectal exams, body mass index and other factors. Using regression analysis, they compared risk factors for men found to have prostate cancer with those for men whose biopsies were negative.
Younger at Diagnosis
“For veterans exposed to Agent Orange, age becomes a significant factor earlier than for those who have not been exposed,” said Ansbaugh. “On average, we found that of the men diagnosed with prostate cancer, those exposed to Agent Orange were about five years younger than those who were not.”
The research showed an average age at diagnosis of 61.4 years for exposed men (95% CI, 60.0 to 61.2), whereas unexposed men were 66.1 years (95% CI, 65.6 to 66.6).
“Our findings supported a 2008 study showing increased risk of prostate cancer associated with Agent Orange exposure and that the cancer occurs at an earlier age,” noted Ansbaugh.
The 2008 study, conducted at the University of California Davis, looked at 6,214 Vietnam veterans who were exposed to the defoliate and 6,930 who were not. Researchers in that study reported that veterans exposed had double the risk of developing prostate cancer compared to those who were not exposed. Like Ansbaugh’s research, the California study also showed that prostate cancer was diagnosed earlier in men exposed to Agent Orange and that three times as many had metastatic cancer at diagnosis. The report can be found in the November 2008 issue of Cancer.
The new study was more specific . “Our study looked only at individuals who were suspected of having prostate cancer, rather than a randomized population,” noted Ansbaugh.
Many other studies have examined the connection between Agent Orange and prostate cancer. Results have consistently identified the defoliate as a risk factor, but its significance has varied. As Vietnam veterans are now entering the age group typically diagnosed with prostate cancer, identification of risk factors is even more important.
“We’re looking at the association between Agent Orange exposure and the risk of high-grade cancer now,” said Ansbaugh.
“We know it increases the risk of prostate cancer in general, but it’s still hard for a clinician to know what to do. If it increases the risk of high-grade cancer, physicians will definitely want to screen those individuals earlier because of the increased complications,” Ansbaugh added.
The results of Ansbaugh’s current research will be presented at the American Society of Clinical Oncology conference in Chicago in June.
Most Common Male Cancer
Prostate cancer is the most common cancer among American men. It affects 156.9 men per 100,000, or more than 220,000 men each year in this country. Prostate cancer is also the second-leading cause of cancer death in American men, behind only lung cancer in nearly all races. It accounts for nearly one-fourth of all male cancer deaths, killing about 30,000 men annually.
Despite the frequency of occurrence, screening all men for prostate cancer is controversial. While aggressive screening can detect prostate cancer early, when treatment is most effective, it can also lead to treatment of slow-growing or low-grade cancers that may have little adverse effect on the men diagnosed with the disease. In addition, the side effects of treatment can include incontinence, bowel dysfunction, erectile dysfunction, infertility, as well as other complications of hormone therapy and chemotherapy.
Consequently, determining whether the prostate cancer associated with Agent Orange is high grade or aggressive would be important in determining the proper recommendations for on-going screening.
Federal agencies have adopted the prostate cancer screening guidelines established by the U.S. Preventive Services Task Force (USPSTF), created by the Agency for Healthcare Research and Quality. USPSTF’s policy statements assert that insufficient scientific evidence exists to support prostate cancer screening for men younger than 75 years old. Men in high-risk categories are advised to be screened for prostate cancer at an earlier age.
Covered by ‘Presumptive Policy’
According to the Department of Veteran Affairs, “the VA presumes that all military personnel who served in Vietnam were exposed to Agent Orange, and federal law presumes that certain illnesses are a result of that exposure.” Prostate cancer is one of the diseases covered under this “presumptive policy” for the 2.6 million men and women who served in combat areas in Vietnam between 1962 and 1975. Others include acute and subacute peripheral neuropathy, AL amyloidosis, chloracne, chronic B-cell leukemias, Type 2 diabetes mellitus, Hodgkins disease, ischemic heart disease, multiple myeloma, non-Hodgkin’s lymphoma, Parkinson’s disease, porphyria cutanea tarda, respiratory cancers, and soft-tissue sarcoma.
The U.S. military herbicide program in South Vietnam took place between 1961 and 1971 with more than 19 million gallons of various herbicide combinations used. Agent Orange was the combination of herbicides used most often by the U.S. VA also considers exposure possible in areas outside of Vietnam such as Thailand air bases, ships at sea, Agent Orange storage facilities and the Korean demilitarized zone.
Accounting for nearly a third of all cancer diagnoses, prostate cancer is the most frequently diagnosed cancer in the VHA, where past research has suggested that the malignancy is caught earlier than in other healthcare systems.
In the past five years, 10 new system therapies have been approved for renal cell carcinoma (RCC), the most common type of kidney cancer.