Biological and Environmental modifiers of Vitamin D3 and Prostate Cancer Risk

摘要 前列腺癌(PCa)的差异是由遗传易感性、 个人风险因素和环境因素。前列腺癌是所有死亡中的第二大死因 男性；然而，非裔美国人(AA)男性的前列腺癌死亡率是所有种族/民族中最高的 这一死亡率差异占整个癌症死亡率差异的44% 在AA和欧洲裔美国人(EA)之间。因此，迫切需要探讨其病因。 造成这种差异的途径。不幸的是，唯一公认的风险因素(年龄、 种族和家族历史)对于PCA是不可修改的。然而，最近的研究发现，低水平的 维生素D与前列腺癌风险增加有关，而维生素D的治疗减少了 多项研究中的前列腺癌疾病进展。这些研究支持这样的假设：维生素D 缺乏维生素D会增加前列腺癌的风险，维生素D是一种潜在的化学预防和治疗方法 探员。虽然遗传和环境因素包括常见的低渗透等位基因、饮食、身体 体重指数(BMI)和维生素D水平可能会影响风险，它们的重要性和多重联合影响是 不清楚。有大量数据支持维生素D3[25(OH)维生素D]在前列腺癌中的关键作用 风险。然而，很难确定它的重要性，主要是因为维生素D是在体内合成的 皮肤和血清水平受肤色、遗传血统、年龄、BMI和 环境因素，如阳光照射和饮食。这个项目的目标是探索 血清维生素D、紫外线照射、肤色、年龄、体重指数和维生素D相关基因的影响 2,000例AA和2,000例侵袭性前列腺癌风险的合成、代谢和信号转导 2,000名EA人员。年龄在40-79岁之间的男性将从芝加哥的一个医院财团招募， 伊利诺伊大学芝加哥医院系统，芝加哥大学医学中心， 西北纪念医院、约翰·H·斯特罗格·库克县医院和杰西·布朗 退伍军人事务医疗中心。这个项目将提高我们对维生素D的作用的理解 对前列腺癌易感性的影响，特别是在非裔美国人中，如果维生素D较低 AAs水平是AAs和AAs之间PCa发病率和死亡率差异的一部分原因 EAS。更重要的是，鉴于UVR和饮食是普遍的环境暴露，可以 容易修改，了解它们的影响可能会对健康产生广泛的影响。

ABSTRACT Disparities in prostate cancer (Pca) are caused by complex interactions of genetic susceptibility, individual risk factors, and environmental factors. Pca is the second leading cause of death among all men; however African American (AA) men have the highest mortality rate of Pca of any racial/ethnic group in the U.S. This difference in mortality accounts for 44% of the overall cancer mortality disparity between AA and European-American (EA) men. Thus, there is a critical need to explore the etiologic pathways that contribute to this disparity. Unfortunately, the only well-established risk factors (age, race and family history) for Pca are non-modifiable. However recent studies have found low levels of vitamin D have been associated with increased Pca risk, and treatment with vitamin D has reduced Pca disease progression in multiple studies. These studies support the hypothesis that vitamin D deficiency increases the risk of Pca and that vitamin D is a potential chemopreventive and therapeutic agent. Although genetic and environmental factors including common low penetrant alleles, diet, body mass index (BMI), and vitamin D levels may affect risk, their significance and multiple joint effects are unclear. Extensive data exists in support of a critical role for Vitamin D3 [25(OH) vitamin D] on Pca risk. However, it is difficult to determine its importance mainly because Vitamin D is synthesized in the skin, and serum levels are strongly influenced by skin color, genetic ancestry, age, BMI, and environmental factors such as sunlight exposure and diet. The goal of this project is to explore the effects of serum Vitamin D, UVR exposure, skin color, age, BMI, and genes involved in Vitamin D synthesis, metabolism and signaling on Pca and aggressive Pca risk in a study of 2,000 AA and 2,000 EA men. Men aged 40-79 will be recruited from a consortium of Chicago hospitals including, the University Illinois at Chicago Hospital System, University of Chicago Medical Center, Northwestern Memorial Hospital, John H. Stroger Cook County Hospital, and the Jesse Brown Veteran Affairs Medical Center. This project will improve our understanding of the role Vitamin D plays on prostate cancer susceptibility, specifically among African Americans, and if lower vitamin D levels in AAs account for a portion of the disparity in Pca incidence and mortality between AAs and EAs. More importantly, given that UVR and diet are general environmental exposures that can be easily modified, understanding their impact may have broad health implications.