Urologic Oncology: Seminars and Original Investigations
Seminar articleEnvironmental exposures and prostate cancer
Introduction
Prostate cancer (CaP) is currently the most common malignancy and second leading cause of cancer death among U.S. males [1]. Other prevalent cancers in the U.S. have modifiable risk factors involved in their pathogenesis, including lung cancer (cigarette smoking) and cervical cancer (HPV infection). Considerable research has been targeted to identifying similar modifiable risk factors involved in the pathogenesis of CaP. Efforts have largely focused on identifying medications, dietary factors, and environmental exposures related to the development of CaP. Despite these efforts, no definitive link between environmental factors and CaP has been established.
Nevertheless, observations of abnormal CaP incidence in certain subgroups of the population have generated hypotheses that specific environmental factors may play a role in the pathogenesis of CaP. Areas of particular interest include the relationship of CaP incidence to specific occupations, sunlight, and trace minerals. This manuscript reviews the available literature on environmental exposures and CaP.
Section snippets
Agent Orange
Agent Orange, named according to the color of its storage drum, was an herbicide sprayed over the Vietnam jungle by U.S. forces from 1962–1971. The herbicide was disseminated in an effort to cripple opposing forces by eliminating concealing jungle canopy and vital crop supplies. The herbicide was unknowingly contaminated with dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic chemical with known pro-tumorigenic properties. In response to the uncertain effects of this exposure to Vietnam
Farming and pesticides
Farming is an occupation that has been associated with an increased risk of various malignancies, including CaP. Indeed, several meta-analyses have demonstrated an increased risk of CaP and CaP-specific mortality among farmers. Interestingly, this association seems to be limited to North American farmers, whereas, European farmers do not appear to share the same risk [6], [7], [8]. The magnitude of risk is typically modest with cumulative risk in meta-analyses ranging between 1.07 and 1.24 [6],
Ultraviolet radiation and vitamin D
Exposure to ultraviolet radiation (UVR) and consequently serum vitamin D levels have been associated with decreased CaP risk. Hanchette and Schwartz initially demonstrated an inverse association between geographic distribution of UVR and CaP mortality [19]. This observation led further research focusing on surrogates for lifetime UVR exposure and CaP. Luscombe et al. reported that childhood sunburns, regular foreign vacation, and high sunbathing score were protective against development of CaP.
Trace minerals
Increased exposure to trace minerals through occupational exposure, cigarette smoking, and diet has been implicated in the pathogenesis of CaP. One such trace mineral is cadmium, which has been linked to an increased risk of CaP and disease-specific mortality in several, but not all, epidemiologic studies [26], [27], [28], [29], [30]. Competitive inhibition of zinc has been proposed as the mechanism of cadmium carcinogenesis [31]. Studies by Kolonel and Kjellstrom documented non-significant
Rubber industry
Reports concerning CaP risk in men employed in the rubber and tire industry have been generally inconsistent. Bernardinelli et al. found an excess of CaP mortality in Italian rubber workers, while Sorahan et al. actually demonstrated reduced CaP incidence among British tire workers [38], [39]. Several studies have demonstrated nonsignificant increases in CaP incidence and mortality. Straif et al. analyzed cancer mortality in over 8,000 German rubber workers over a 10-year period. The authors
Conclusion
Numerous epidemiologic studies have linked CaP risk to various environmental and occupational exposures (Table 1). Several studies have suggested a relationship between Agent Orange with CaP risk as well as aggressive disease. There is also strong epidemiologic evidence suggesting an inverse relationship between sun exposure and CaP risk. Although farming has been associated with increased CaP risk, the specific underlying mechanisms remain to be established. The data on occupational exposures
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