Date

January 2008

Document Type

Thesis

Degree Name

M.P.H.

Department

Dept. of Public Health and Preventive Medicine

Institution

Oregon Health & Science University

Abstract

Background: Agent Orange (AO), a defoliate contaminated with the known carcinogen dioxin, has become a prominent concern as veterans of the Vietnam War who were exposed to AO are now reaching the age at which they are at greatest risk of developing prostate cancer. While sufficient evidence has linked AO exposure to many diseases, only limited but suggestive evidence exists to support a positive association between AO and prostate cancer. Despite mixed findings, recent studies have found that the risk of prostate cancer in those exposed to AO was as high as twice the risk in those not exposed. The goal of this study was to examine this association between AO exposure and prostate cancer in a cohort of men referred for a prostate biopsy. Methods: In this retrospective cohort-design, risk factors were identified using historical clinical data from a population of veterans referred to the Portland VA Hospital for a prostate biopsy between 1993 and 2010. In addition to AO exposure, covariates included prostate specific antigen density (PSAD), results of the digital rectal exam (DRE), age at biopsy, family history, body mass index (BMI), race, and service history. Outcomes of the biopsies were defined as either positive or negative according to the pathology report and risk factors were compared between individuals found to have prostate cancer and those without cancer. A second analysis compared these risk factors between individuals who were found to have high grade cancer (Gleason ≥ 7) and individuals with low grade cancer (Gleason < 7). Multiple logistic regression was used to evaluate the effect of AO on risk of prostate cancer and high grade prostate cancer after adjustment for confounders. Results: Of the 2720 veterans who underwent prostate biopsy, 896 (32.9%) were found to have prostate cancer and 459 (16.9%) were found to have high grade cancer. After adjustment for significant confounders including PSAD, DRE, age at biopsy, servicem history, and family history of prostate cancer, veterans with AO exposure were 49% more likely to have prostate cancer compared to those without exposure to AO (aOR = 1.49; 95% CI: 1.05 - 2.10, p=.02). Additionally, amongst those with prostate cancer, individuals with exposure to AO were diagnosed with prostate cancer on average roughly 5 years earlier than individuals not exposed to AO (Mean age of diagnosis for AO exposed = 61.4 years; Mean age of diagnosis for non-exposed = 66.1 years, p<0.0001). Individuals with AO exposure were also 70% more likely to have high grade prostate cancer compared to those without AO exposure (aOR = 1.70, 95% CI: 1.10 – 2.55, p = 0.02). Agent Orange appears to be particularly associated with high grade cancer (aOR = 1.70, 95% CI: 1.08 to 2.70, p=0.02 in the analysis of high grade cancer vs. no cancer; aOR = 1.25, 95% CI: 0.81 to 1.92, p = 0.32 in the analysis of low grade cancer vs. no cancer). Conclusions: Agent Orange exposure was associated with a significant increase in risk of prostate cancer and, more specifically, high grade cancer among men referred for a prostate biopsy. The limitations in identifying biologically significant levels of AO exposure in this study may suggest potential for underestimation of the true risk. Agent Orange exposure was associated with a significant increase in the risk of high-grade prostate cancer in men referred for an initial prostate biopsy. If validated, these findings could have significant implications in the development of effective prostate cancer screening strategies for male Veterans.

Identifier

doi:10.6083/M4CC0XP5

School

School of Medicine

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