Review article
A review of Agent Orange and its associated oncologic risk of genitourinary cancers

https://doi.org/10.1016/j.urolonc.2017.08.029Get rights and content

Highlights

  • Increased association between Agent Orange and prostate cancer.

  • Increased association between Agent Orange and bladder cancer.

  • Inconclusive evidence linking Agent Orange and renal and testicular cancers.

Abstract

Agent Orange is an herbicide sprayed widely in Vietnam that is linked to a variety of malignancies in as early as 1991.Since then, there has been concern for, and subsequent interest in studying, the potential connection between Agent Orange and other malignancies. In the past 2 decades, there have been significant changes in the opinion of the National Academy of Science regarding Agent Orange and certain genitourinary malignancies. Herein, we review the literature regarding the potential link between Agent Orange and various urological cancers, including prostate, bladder, testicular, and renal cancers.

Section snippets

Background

Agent Orange is an herbicide sprayed widely in Vietnam from August 1965 to February 1971, and contains 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD has been shown to cause direct DNA damage and has been linked to a variety of malignancies, especially non–Hodgkin’s lymphomas, soft-tissue sarcomas, and cutaneous T-cell lymphomas [1], [2]. With these discoveries, there was significant concern that Agent Orange could increase the risk of other cancers as well. In recent years, there has been

Biological plausibility of Agent Orange and malignancy

Several studies have provided significant evidence corroborating TCDDs association with malignancy. TCDD is easily and rapidly absorbed via alimentary tract, yet eliminated slowly. Oral administration can lead to 50% to 93% absorption of the administered dose [5]. The half-life is exceedingly long, with some studies demonstrating a half-life of up to 7.2 years [6]. The mechanism by which TCDD promotes carcinogenesis has not been completely elucidated, but it is known that TCDD interacts

Prostate cancer

Prostate cancer has been the most common noncutaneous malignancy in the United States since 1984, now accounting for 27% of all cancers and it is estimated that 1 in 7 men alive today will be diagnosed with prostate cancer [8]. The first study demonstrating an associated increased risk of prostate cancer due to Agent Orange exposure was a case-control study in 2004 at the Michigan Veterans Affairs hospital, which showed that men with prostate cancer were approximately 2 times more likely to

Bladder cancer

Bladder cancer is a “cancer of the environment and age” [22]. Links confirming genetic susceptibility to bladder cancer have been made, such as NAT2 slow acetylator and GSTM1-null genotypes [23]; however, external risk factors appear to be of primary importance. The earliest chemical agents associated with bladder cancer were Benzidine and β-naphthylamine in dye and rubber workers [24]. However, the most important known risk factor for bladder cancer is tobacco smoke inhalation. Over the past

Testicular cancer

Testicular cancer occurs most often in men between the ages of 20 and 34 [31]. Known risk factors for testicular cancer include white race [31], cryptorchidism [32], family history [33], [34], and infertility [35]. Agent Orange as a risk factor for the development of testicular cancer has not been thoroughly explored, likely due to the early presentation and rarity of the disease.

The most recent study, conducted by Yi and Ohrr, examined Korean Vietnam Veterans (high exposure n = 85,809 vs. low

Renal cancer

Renal cancer occurs predominantly in the sixth to eighth decades of life, is uncommon in patients younger than 40 years, and is rare in children [43]. It is estimated that in the United States, 39,650 men and 23,050 women will be diagnosed with renal cancer in 2016, and that 9,240 men and 5,000 women will die from it [44]. Numerous risk factors have been implicated in renal cancer including tobacco use, occupational exposure to toxic compounds such as cadmium, asbestos, and petroleum

Discussion

Agent Orange, an herbicide used during the Vietnam War, contains compounds such as TCDD that have been linked to an increased incidence of malignancies. Although TCDDs association with urological malignancies has only recently been explored, there is “limited or suggestive evidence” of an increased association between Agent Orange and prostate and bladder cancer [4]. Agent Orange is linked not only to an increased incidence in prostate cancer, but also to a higher grade cancer in exposed

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