Prostate Cancer Detection in Veterans With a History of Agent Orange Exposure

Zafar, Muhammad Behzad; Terris, Martha K.

doi:10.1016/s0022-5347(05)66085-5

Cited by 22 publications

(29 citation statements)

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“…Zafar and Terris evaluated patients who were referred for prostate biopsy. 8 Of 400 patients who were referred for biopsy in that study, 32 patients reported exposure to Agent Orange. Although Zafar and Terris observed a slightly increased rate of prostate cancer in the group with Agent Orange exposure (41% vs 34%), the increase was not statistically significant.…”

Section: Discussionmentioning

confidence: 97%

“…Although there is sufficient evidence linking soft tissue sarcomas, Hodgkin disease, and non-Hodgkin lymphoma with Agent Orange exposure, 4 evidence of the risk of subsequent prostate cancer has been much less robust. [5][6][7][8][9][10] Operation Ranch Hands, a longitudinal study that was conducted on Air Force veterans, identified no increased incidence of prostate cancer compared with a similar cohort of veterans. However, that study did observe an increased risk compared with the standard US population of white men.…”

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confidence: 99%

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Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

Chamie

White

Lee

et al. 2008

Cancer

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BACKGROUND. It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006. METHODS. All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n = 6214) or unexposed (n = 6930) to Agent Orange. Strata‐specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate‐specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi‐square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression. RESULTS. Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75‐2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31‐3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange‐exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9‐60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8‐63.6 years), had a 2‐fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%‐27%) compared with unexposed men (10.5%; 95% CI, 5%‐15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%‐17.7%) than unexposed men (4%; 95% CI, 0.5%‐7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high‐grade and metastatic disease on presentation. CONCLUSIONS. Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as ‘high risk,’ just like men of African‐American heritage and men with a family history of prostate cancer. Cancer 2008. © 2008 American Cancer Society.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

Chamie

White

Lee

et al. 2008

Cancer

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“…A prevalence study was conducted among 400 Vietnam veterans referred for prostate biopsy (Zafar and Terris, 2001). Thirty-two veterans who reported Agent Orange exposure were compared to a sample of 96 unexposed veterans.…”

Section: Review Of Epidemiologic Studiesmentioning

confidence: 99%

TCDD and cancer: A critical review of epidemiologic studies

Boffetta

Mundt

Adami

et al. 2011

Critical Reviews in Toxicology

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The authors reviewed the epidemiologic studies on exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer risk, published since the last full-scale review made by the International Agency for Research on Cancer Monographs program in 1997. The update of a cohort of US herbicide producers generated negative results overall; the internal analysis provided evidence of an increased “all-cancer” risk in the highest exposure category, with a statistically significant exposure-response association in some of the many analyses performed.The update of a similar Dutch cohort did not confirm the previously observed association with TCDD exposure. The updated surveillance of the Seveso population provided evidence of increased all-cancer mortality 15-20 years after exposure among those living in the most contaminated area but might also reflect random variation, as overall excesses in the most recent follow-up were not observed. Corresponding data on cancer incidence offer little support to the mortality results. Updated results from cohort studies of Vietnam veterans potentially exposed to TCDD did not consistently suggest an increased risk of cancer. Results of additional, smaller studies of other occupational groups potentially exposed to TCDD, and of community-based case-control studies, did not provide consistent evidence of an increased cancer risk. In conclusion, recent epidemiological evidence falls far short of conclusively demonstrating a causal link between TCDD exposure and cancer risk in humans. The emphasis on results for overall cancer risk—rather than risk for specific neoplasms—is notjustified on epidemiologic grounds and is nota reason for ignoring the weaknesses of the available evidence.

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“…Early studies failed to show a significant association between AOe and PCa detection 12,13 ; however, the majority of studies including larger more recent studies have shown a positive association with PCa 10–13 . The small sample size in the studies finding positive but not statistically significant associations warrants caution as Type II error could account for these non-significant findings since these studies were not powered to find an association with the strength we observed in our study.…”

Section: Discussionmentioning

confidence: 95%

“…The effect of AOe on the risk of PCa detection has been an area of some scientific debate. Early studies failed to demonstrate a significant association between AOe and PCa detection 12,13 ; however, the majority of studies, including larger, more recent studies, have demonstrated a positive association between AOe and PCa. [10][11][12][13] The small sample sizes in the studies that reported positive but statistically nonsignificant associations warrant caution, because a type II error may account for these nonsignificant findings, in that those studies were not powered to identify an association with the strength we observed in our current study.…”

Section: Discussionmentioning

confidence: 98%

Agent Orange as a risk factor for high‐grade prostate cancer

Ansbaugh

Shannon

Mori

et al. 2013

Cancer

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PURPOSE Agent Orange exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. This study aimed to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa, Gleason ≥ 7) on biopsy in a US Veteran cohort. METHODS Risk factors included clinico-demographic and laboratory data from veterans referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa, Gleason ≤6) in biopsy specimens. Risk amongst AOe veterans relative to unexposed veterans was estimated with multivariate logistic regression. Separate models determined whether AOe was associated with an increased risk of PCa, HGPCa or LGPCa. RESULTS Of 2720 Veterans biopsied, PCa was diagnosed in 896 (32.9%); 459 (16.9%) had HGPCa. AOe was associated with a 52% increase in overall risk of PCa detection (aOR = 1.52, 95% CI: 1.07–2.13). AOe did not confer an increase in risk of LGPCa (aOR = 1.24, 95% CI: 0.81 to 1.91), although a 75% increase in risk of HGPCa (aOR = 1.75, 95% CI: 1.12 to 2.74) was observed. AOe was associated with a 2.1 fold increase (95% CI: 1.22 to 3.62, p<0.01) in Gleason 8 or higher PCa. CONCLUSION The increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men undergoing initial prostate biopsy. These findings could aid in improved PCa screening for Vietnam-era Veterans.

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Prostate Cancer Detection in Veterans With a History of Agent Orange Exposure

Abstract: Agent Orange may have a role in the causation of some types of cancer but we identified no significant relationship of prostate cancer with Agent Orange exposure in patients referred for prostate biopsy.

Cited by 22 publications

References 14 publications

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

TCDD and cancer: A critical review of epidemiologic studies

Agent Orange as a risk factor for high‐grade prostate cancer

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