Biological and Environmental modifiers of Vitamin D3 and Prostate Cancer Risk

维生素 D3 的生物和环境调节剂与前列腺癌风险

• 批准号: 8618794
• 负责人: RICK A. KITTLES
• 金额: $ 39.88万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-11 至 2014-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8618794
• 关键词: 25-hydroxyvitamin D; Academic Medical Centers; Accounting; Affect; African; African American; Age; Alleles; American; Apoptosis; Area; Attention; Biological; Blood; Body mass index; Calcium; Cancer Etiology; Cancer Patient; Candidate Disease Gene; Cause of Death; Cell division; Cells; Chemopreventive Agent; Chicago; Cholecalciferol; Clinical; Colon Carcinoma; Complex; County Hospitals; DNA; Data; Diet; Disease; Disease Progression; Enrollment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Ethnic Origin; Ethnic group; European; Family; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Goals; Growth; Haplotypes; Health; Hospitals; Illinois; Incidence; Individual; Institution; Intake; Joints; Linear Regressions; Link; Literature; Logistic Regressions; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical center; Metabolism; Methods; Modeling; Newly Diagnosed; PC3 cell line; Participant; Pathogenesis; Pathway interactions; Patients; Physiological; Play; Population; Predisposition; Prospective Studies; Prostate; Questionnaires; Race; Recording of previous events; Recruitment Activity; Reporting; Risk; Risk Factors; Role; Serum; Signal Transduction; Skin; Skin Pigmentation; Study of serum; Subgroup; Sun Exposure; System; Testing; Therapeutic Agents; Time; UV Radiation Exposure; Ultraviolet Rays; United States; United States National Institutes of Health; Universities; University Hospitals; Veterans; Vitamin D; Vitamin D Deficiency; Vitamins; Work; aged; base; cancer risk; case control; cooking; design; genome sequencing; improved; male; malignant breast neoplasm; men; mortality; racial and ethnic; skin color

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.

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。PCA是所有死亡原因中的第二大死因 男性;然而，非洲裔美国人（AA）男性的PCA死亡率在所有种族/民族中最高 这种死亡率的差异占整体癌症死亡率差异的44% AA和欧洲-美国（EA）男性之间的差异。因此，迫切需要探索病因学 导致这种差异的途径。不幸的是，唯一确定的风险因素（年龄， 种族和家族史）是不可改变的。然而，最近的研究发现， 维生素D与Pca风险增加有关，维生素D治疗降低了Pca风险。 多项研究中的Pca疾病进展。这些研究支持了维生素D 缺乏维生素D会增加Pca的风险，维生素D是一种潜在的化学预防和治疗药物。 剂虽然遗传和环境因素包括常见的低外显等位基因、饮食、身体 体重指数（BMI）和维生素D水平可能会影响风险，其意义和多重联合作用是 不清楚存在大量数据支持维生素D3 [25（OH）维生素D]对Pca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。本项目的目标是探索 血清维生素D、紫外线照射、肤色、年龄、BMI和维生素D相关基因的影响 在2，000例AA研究中， 两千EA的人年龄在40-79岁之间的男性将从芝加哥医院联盟招募，包括， 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 前列腺癌的易感性，特别是在非洲裔美国人中， AA水平是AA和AA之间Pca发病率和死亡率差异的一部分。 EA。更重要的是，考虑到紫外线和饮食是一般的环境暴露， 由于它们很容易改变，了解它们的影响可能会对健康产生广泛的影响。