| Inorganic Arsenic and Human Prostate
Cancer Lamia Benbrahim-Tallaa and Michael P.
Waalkes Inorganic Carcinogenesis Section,
Laboratory of Comparative Carcinogenesis, National Cancer
Institute at the National Institute of Environmental Health
Sciences, National Institutes of Health, Department of Health
and Human Services, Research Triangle Park, North Carolina,
USA Abstract
Objective: We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data sources: We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis: Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose–response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion: Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important. Key words: androgen-independent, AR, arsenic, carcinogenesis, DNA methylation, human malignant transformation, MAP kinase, prostate, Ras. Environ Health Perspect 116: 158–164 (2008) . doi:10.1289/ehp.10423 available via http://dx.doi.org/ doi:10.1289/ehp.10423 available via http://dx.doi.org/ [Online 8 November 2007]
Address correspondence to M.P. Waalkes, Inorganic Carcinogenesis Section, NCI at NIEHS, MD F0-09, 111 Alexander Dr., Research Triangle Park, NC 27709 USA. Telephone: (919) 541-2328. Fax: (919) 541-3970. E-mail: waalkes@niehs.nih.gov We thank J. Liu and E. Tokar for their critical review of this manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors declare they have no competing financial interests. Received 1 May 2007 ; accepted 8 November 2007.
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