Rishi Irum, Baidouri Hasna, Abbasi Jamil A, Bullard-Dillard Rebecca, Kajdacsy-Balla Andre', Pestaner Joseph P, Skacel Marek, Tubbs Raymond, Bagasra Omar
University of South Carolina Cancer Research Center, Columbia, SC, USA.
Appl Immunohistochem Mol Morphol. 2003 Sep;11(3):253-60. doi: 10.1097/00129039-200309000-00009.
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.
在美国，前列腺癌是最常被诊断出的男性癌症，也是所有男性癌症死亡的第二大原因。此外，非裔美国人的发病率高于任何其他种族群体。我们的实验室正在试图破解非裔美国人前列腺癌发生过程中涉及的环境和分子机制。由于非洲是一个矿产丰富的大陆，水和饮食中的锌含量很高，因此推测非洲人可能在基因上降低了他们吸收锌的能力；否则，他们会吸收异常高水平的锌，导致各种严重的神经退行性和生化紊乱。因此，由于锌转运蛋白的固有下调，非洲裔人群与其他种族群体相比，可能具有较低的锌吸收能力。广泛的研究表明，血清锌水平低与前列腺癌发病率增加有关。我们评估了2个主要种族群体中的58个前列腺癌组织（30个来自白人，28个来自非裔美国人）表达2种主要人类锌转运蛋白hZIP1和hZIP2的能力。在从白人获得的所有30个前列腺癌标本中，与从非裔美国患者获得的年龄匹配和Gleason评分匹配的标本相比，这2种锌受体的表达程度较高。我们还发现，与年龄匹配的白人男性相比，非裔美国男性正常前列腺组织中这2种锌转运蛋白显著下调。失去维持细胞内锌正常水平的独特能力可能是前列腺癌发生和发展的一个重要因素。我们观察到不同种族群体对锌的摄取可能不同，这一发现既有趣又有意义。一旦这些数据在更大的群体中得到证实，这一发现至少对某些人作为一种预防措施可能具有重要应用价值。由于膳食锌补充剂相对无毒，任何疗效试验的风险都较低。
