Abstract
Background:
Agent Orange (AO) was previously identified as a significant risk factor for biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer patients. In this study, we determined the levels of dioxin biological toxicity using toxic equivalency (TEQ) values and examined the impact of dioxin-TEQ level on BCR.
Methods:
A total of 93 men who underwent RP, with a median of 5.3 years of postoperative follow-up, were included in the study. The dioxin-TEQ level of each patient was measured using intraoperatively harvested abdominal subcutaneous fat. The dichotomous categorization of dioxin-TEQ by the 50th percentile (low<50% vs high⩾ 50%) was also used to regroup the patient cohort, regardless of the previous history of AO exposure. Comparisons between the dioxin-TEQ levels, clinicopathological characteristics and BCR in AO-exposed and -unexposed men were made to allocate possible risk factors. The multivariable logistic regression model was used to identify significant risk factors associated with BCR, adjusting for other confounding factors.
Results:
The median dioxin-TEQ level in 37 AO-exposed patients was significantly higher than that in 56 unexposed patients (22.3 vs 15.0 pg g−1 fat, respectively, P<0.001). The men with AO exposure were more likely to have a high dioxin-TEQ level (P<0.001). Neither AO exposure nor the level of dioxin-TEQ was associated with BCR. Tumor stage (T3/T4 vs T2) and Gleason grade (Gleason ⩾3+4) were independent risk factors for BCR after RP.
Conclusions:
Exposure to AO significantly increases the adipose level of dioxin-TEQ in patients treated with RP. However, exposure to AO or a high dioxin-TEQ level was not associated with an increased risk of BCR after RP. This lack of association supports the current conclusion that the evidence of carcinogenicity of AO in prostate cancer patients is not sufficient and remains ‘limited’.
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References
Institute of Medicine. Veterans and Agent Orange: health effects of herbicides used in Vietnam. National Academy Press: Washington DC, 1994.
Institute of Medicine (IOM). Veterans and Agent Orange: Update 2008. National Academy Press: Washington DC, 2009.
Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M et al. The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci 93: 223–241.
Michalek JE, Tripathi RC . Pharmacokinetics of TCDD in veterans of Operation Ranch Hand: 15-year follow-up. J Toxicol Environ HealthA 1999; 57: 369–378.
Schecter A, Dai LC, Thuy LT, Quynh HT, Minh DQ, Cau HD et al. Agent Orange and the Vietnamese: the persistence of elevated dioxin levels in human tissues. Am J Public health 1995; 85: 516–522.
Zafar MB, Terris MK . Prostate cancer detection in veterans with a history of Agent Orange exposure. J Urol 2001; 166: 100–103.
Giri VN, Cassidy AE, Beebe-Dimmer J, Ellis LR, Smith DC, Bock CH et al. Association between Agent Orange and prostate cancer: a pilot case-control study. Urology 2004; 63: 757–760 discussion 760-751.
Chamie K, DeVere White RW, Lee D, Ok JH, Ellison LM . Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer 2008; 113: 2464–2470.
Shah SR, Freedland SJ, Aronson WJ, Kane CJ, Presti JC Jr., Amling CL et al. Exposure to Agent Orange is a significant predictor of prostate-specific antigen (PSA)-based recurrence and a rapid PSA doubling time after radical prostatectomy. BJU Int 2009; 103: 1168–1172.
Kane CJ, Im R, Amling CL, Presti JC Jr., Aronson WJ, Terris MK et al. Outcomes after radical prostatectomy among men who are candidates for active surveillance: results from the SEARCH database. Urology 2010; 76: 695–700.
Akhtar FZ, Garabrant DH, Ketchum NS, Michalek JE . Cancer in US Air Force veterans of the Vietnam War. J Occup Environ Med 2004; 46: 123–136.
Pavuk M, Michalek JE, Ketchum NS . Prostate cancer in US Air Force veterans of the Vietnam war. J Exposure Sci environ epidemiol 2006; 16: 184–190.
Savdie R, Horvath LG, Benito RP, Rasiah KK, Haynes AM, Chatfield M et al. High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy. BJU int 2012; 109: 1794–1800.
Budaus L, Isbarn H, Eichelberg C, Lughezzani G, Sun M, Perrotte P et al. Biochemical recurrence after radical prostatectomy: multiplicative interaction between surgical margin status and pathological stage. J Urol 2010; 184: 1341–1346.
Boffetta P, Mundt KA, Adami HO, Cole P, Mandel JS . TCDD and cancer: a critical review of epidemiologic studies. Crit Rev Toxicol 2011; 41: 622–636.
Tuomisto J, Tuomisto JT . Is the fear of dioxin cancer more harmful than dioxin? Toxicology Lett 2012; 210: 338–344.
Kahn PC, Gochfeld M, Nygren M, Hansson M, Rappe C, Velez H et al. Dioxins and dibenzofurans in blood and adipose tissue of Agent Orange-exposed Vietnam veterans and matched controls. JAMA 1988; 259: 1661–1667.
Acknowledgements
We thank William Kingsberry of the AO Office at the Charlie Norwood Veterans Affairs Medical Center for providing information regarding patients’ history of AO exposure and the duration of service at an AO-sprayed area. Funding Support: This study was funded by the Georgia Cancer Coalition.
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The authors declare no conflict of interest. The opinions expressed in this article are those of the authors and do not necessarily reflect the policies of the US Environmental Protection Agency or the Centers for Disease Control and Prevention or the US Department of Veterans Affairs.
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Li, Q., Lan, L., Klaassen, Z. et al. High level of dioxin-TEQ in tissue is associated with Agent Orange exposure but not with biochemical recurrence after radical prostatectomy. Prostate Cancer Prostatic Dis 16, 376–381 (2013). https://doi.org/10.1038/pcan.2013.33
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DOI: https://doi.org/10.1038/pcan.2013.33
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