Prostate cancer in African American men is associated with downregulation of zinc transporters.

In the United States, prostate cancer is the most commonly diagnosed male cancer and the second leading cause of all male cancer deaths. Furthermore, incidence rates are higher in African Americans than in any other racial group. Our laboratory is attempting to decipher the environmental and molecular mechanisms involved in the development of prostate cancer in African Americans. Because Africa is a mineral-rich continent, and the zinc levels in the water and diet are high, it is hypothesized that Africans may have genetically downregulated their zinc absorption capacity; otherwise, they would absorb abnormally high levels of zinc, resulting in various serious neurodegenerative and biochemical disorders. It is therefore possible that people of African origin may have a lower capacity to absorb zinc when compared with other racial groups because of their inherent downregulation of zinc transporters. Extensive research has shown that low serum levels of zinc are associated with the increased incidence of prostate cancer. We have evaluated 58 prostate cancer tissues in 2 major racial groups (30 from whites and 28 from African Americans) for their ability to express 2 major human zinc transporters, hZIP1 and hZIP2. In all 30 prostate cancer specimens obtained from white people, the degree of expression of these 2 zinc receptors was high when compared with age-matched and Gleason score-matched specimens obtained from African American patients. We also found a significant downregulation of these 2 zinc transporters in normal prostate tissues from African American men when compared with age-matched white men. The loss of the unique ability to retain normal intracellular levels of zinc may be an important factor in the development and progression of prostate cancer. Our observation that the uptake of zinc may be different in racial groups is intriguing and relevant. Once these data are confirmed in larger groups, this finding could have significant application as a preventive maneuver for at least for some people. Because dietary zinc supplements are relatively nontoxic, any efficacy trial would be low-risk.