In the JournalsPerspective

Agent Orange exposure may increase prostate cancer risk

A history of Agent Orange exposure was associated with a 75% increase in the risk for life-threatening high-grade prostate cancer, according to a cohort analysis of US veterans.

However, exposure to the herbicide did not increase the risk for low-grade prostate cancer.

Prior studies have suggested an association between exposures to Agent Orange — a commercially manufactured defoliate sprayed extensively during the Vietnam War — and the incidence of soft tissue sarcoma, Hodgkin’s disease and non-Hodgkin’s lymphoma among veterans. There also is limited evidence for possible Agent Orange association with the development of respiratory cancer, multiple myeloma and prostate cancer.

Researchers conducted the current study to evaluate the risk for prostate cancer and high-grade prostate cancer among veterans with Agent Orange exposure. They also hoped to assess whether exposure is associated with a unique increase in high-grade prostate cancer or has an identical effect on low-grade prostate cancer risk.

The analysis included 2,720 veterans who underwent initial prostate biopsy.

Veterans were classified as either ‘‘exposed’’ or ‘‘unexposed’’ in accordance with the local Veterans Affairs Medical Center standards for documenting Agent Orange exposure. Those who did not have available exposure status were classified as unexposed. Only nine (0.3%) veterans did not have clearly declared exposure status.

Prostate cancer risk in those with Agent Orange exposure was 52% greater (adjusted OR=1.52; 95% CI, 1.07-2.13) than the prostate cancer risk in those without Agent Orange exposure, according to study results.

Veterans with Agent Orange exposure exhibited a 74% greater risk for high-grade prostate cancer compared with those who were not exposed to Agent Orange (adjusted OR=1.74; 95% CI, 1.14-2.63). However, Agent Orange exposure was not found to contribute to the risk for low-grade prostate cancer (adjusted OR=1.24; 95% CI, 0.81-1.91).

In addition, Agent Orange exposure was linked to a 2.1-fold increase (95% CI, 1.22-3.62) in the risk of detecting prostate cancer with a Gleason score ≥8.

“Biomarkers for the prediction of life-threatening disease are needed to improve current [prostate cancer] screening strategies,” the researchers wrote. “In our study, a history of [Agent Orange exposure] was associated with a 75% increase in the risk of life-threatening [prostate cancer], but it was not associated significantly with an increase in [low-grade prostate cancer]. Incorporating [Agent Orange exposure] history into decision-making for [prostate cancer] screening among veterans may help to better predict clinically significant [prostate cancer] while not adding to the number of clinically insignificant [prostate cancer] diagnoses.”

Disclosure: The researchers reported no relevant financial disclosures.

A history of Agent Orange exposure was associated with a 75% increase in the risk for life-threatening high-grade prostate cancer, according to a cohort analysis of US veterans.

However, exposure to the herbicide did not increase the risk for low-grade prostate cancer.

Prior studies have suggested an association between exposures to Agent Orange — a commercially manufactured defoliate sprayed extensively during the Vietnam War — and the incidence of soft tissue sarcoma, Hodgkin’s disease and non-Hodgkin’s lymphoma among veterans. There also is limited evidence for possible Agent Orange association with the development of respiratory cancer, multiple myeloma and prostate cancer.

Researchers conducted the current study to evaluate the risk for prostate cancer and high-grade prostate cancer among veterans with Agent Orange exposure. They also hoped to assess whether exposure is associated with a unique increase in high-grade prostate cancer or has an identical effect on low-grade prostate cancer risk.

The analysis included 2,720 veterans who underwent initial prostate biopsy.

Veterans were classified as either ‘‘exposed’’ or ‘‘unexposed’’ in accordance with the local Veterans Affairs Medical Center standards for documenting Agent Orange exposure. Those who did not have available exposure status were classified as unexposed. Only nine (0.3%) veterans did not have clearly declared exposure status.

Prostate cancer risk in those with Agent Orange exposure was 52% greater (adjusted OR=1.52; 95% CI, 1.07-2.13) than the prostate cancer risk in those without Agent Orange exposure, according to study results.

Veterans with Agent Orange exposure exhibited a 74% greater risk for high-grade prostate cancer compared with those who were not exposed to Agent Orange (adjusted OR=1.74; 95% CI, 1.14-2.63). However, Agent Orange exposure was not found to contribute to the risk for low-grade prostate cancer (adjusted OR=1.24; 95% CI, 0.81-1.91).

In addition, Agent Orange exposure was linked to a 2.1-fold increase (95% CI, 1.22-3.62) in the risk of detecting prostate cancer with a Gleason score ≥8.

“Biomarkers for the prediction of life-threatening disease are needed to improve current [prostate cancer] screening strategies,” the researchers wrote. “In our study, a history of [Agent Orange exposure] was associated with a 75% increase in the risk of life-threatening [prostate cancer], but it was not associated significantly with an increase in [low-grade prostate cancer]. Incorporating [Agent Orange exposure] history into decision-making for [prostate cancer] screening among veterans may help to better predict clinically significant [prostate cancer] while not adding to the number of clinically insignificant [prostate cancer] diagnoses.”

Disclosure: The researchers reported no relevant financial disclosures.

    Perspective

    • Ansbaugh and colleagues describe an interesting retrospective analysis of 2,720 veterans who underwent prostate biopsy at the Portland Oregon VA Medical Center. The authors sought to evaluate whether a history of Agent Orange exposure influenced the risk of having a positive biopsy and prognostic features of cancers diagnosed. Prostate cancer was diagnosed in 896 veterans (32.9%), and 459 veterans (16.9%) had prostate cancer, Gleason grade ≥8.

      Agent Orange exposure was associated with a 52% increase in the overall risk of detecting prostate cancer (adjusted OR=1.52; 95% CI, 1.07-2.13). Agent Orange exposure did not confer an increased risk of low-grade prostate cancer (adjusted OR=1.24; 95% CI, 0.81-1.91). Agent Orange exposure was associated with a 2.1-fold increase (95% CI, 1.22-3.62) in the risk of detecting prostate cancer with a Gleason score ≥8. These investigators report a carefully conducted retrospective evaluation.

      As with all such studies, the conclusions are complicated by the reliance on retrospective history and recall of Agent Orange exposure; reducing that concern is the care that our VA System has taken to document Agent Orange exposure. Also a plus is the robust VA EMR system that facilitated medical record analysis in these patients. These results complement the extensive Institute of Medicine analysis published in 2010; this analysis included a 274-page “chapter” on the analysis of the data on the association of Agent Orange exposure and cancer.

      The IOM concluded that the evidence supported an association between Agent Orange exposure and B-cell lymphomas and leukemias. However, for prostate cancer, the evidence was found to be “suggestive” but not conclusive. The analysis of Ansbaugh and colleagues provides important information consistent with an important relationship. Confirmatory research is needed, but given the uncertainty regarding factors that should influence how to decide in what individuals to perform a prostate biopsy, careful consideration should be given to incorporating a history of Agent Orange exposure in the decision matrix — such patients may well be at greater risk of high-grade cancer. The interaction of Agent Orange exposure and other risk factors, such as African-American descent and positive family history, will be important to evaluate.
      • Donald L. Trump, MD, FACP
      • HemOnc Today Editorial Board member