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: 8283201
• 负责人: RICK A. KITTLES
• 金额: $ 39.23万
• 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 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8283201
• 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

DESCRIPTION (provided by applicant): 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 a 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. PUBLIC HEALTH RELEVANCE: Vitamin D has been shown to induce differentiation of prostate cells and to inhibit growth and induce apoptosis in prostate cancer cell lines. There has been epidemiologic evidence linking vitamin D status to breast, colon and prostate cancer. Prospective studies have been lacking and among the literature there have been inconclusive results. Notably, these studies are lacking in numbers of men of African ancestry who are likely to have aggressive prostate cancer and to be more vitamin D deficient. Also the studies fail to look at the interaction of vitamin D level, sun exposure, skin color, and genetic variation in genes in the vitamin D synthesis and metabolism pathway. Here we will propose a prospective study of serum vitamin D (25-OH D) levels and prostate cancer risk among African American and European American men aged 40-79. The study will be conducted at five Chicago area institutions, 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 in Chicago.

描述（由申请人提供）：前列腺癌（Pca）的差异是由遗传易感性、个体风险因素和环境因素的复杂相互作用引起的。 前列腺癌是所有男性中的第二大死亡原因;然而，非裔美国人（AA）男性的前列腺癌死亡率是美国任何种族/民族群体中最高的。这种死亡率差异占AA和欧洲-美国人（EA）男性之间总体癌症死亡率差异的44%。因此，迫切需要探索导致这种差异的病因学途径。不幸的是，PCA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，低水平的维生素D与Pca风险增加有关，在多项研究中，维生素D治疗减少了Pca疾病的进展。这些研究支持了维生素D缺乏会增加Pca风险的假设，维生素D是一种潜在的化学预防和治疗剂。虽然遗传和环境因素，包括常见的低渗透等位基因，饮食，体重指数（BMI）和维生素D水平可能会影响风险，但其意义和多重联合效应尚不清楚。大量的数据支持一个关键的 维生素D3 [25（OH）维生素D]对Pca风险的作用。然而，很难确定其重要性，主要是因为维生素D是在皮肤中合成的，血清水平受到肤色，遗传血统，年龄，BMI和环境因素（如阳光照射和饮食）的强烈影响。该项目的目标是在一项对2,000名AA和2,000名EA男性的研究中探索血清维生素D、UVR暴露、肤色、年龄、BMI以及参与维生素D合成、代谢和信号传导的基因对Pca和侵袭性Pca风险的影响。将从芝加哥医院联盟招募40-79岁的男性，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。该项目将提高我们对维生素D在前列腺癌易感性中所起作用的理解，特别是在非洲裔美国人中，如果AA中维生素D水平较低是AA和EA之间Pca发病率和死亡率差异的一部分。更重要的是，鉴于紫外线和饮食是一般的环境暴露，可以很容易地改变，了解他们的影响可能有广泛的健康影响。 公共卫生相关性：维生素D已被证明可以诱导前列腺细胞分化，抑制前列腺癌细胞系的生长并诱导细胞凋亡。有流行病学证据表明，维生素D状况与乳腺癌、结肠癌和前列腺癌有关。缺乏前瞻性研究，文献中也没有结论性结果。值得注意的是，这些研究缺乏可能患有侵袭性前列腺癌和更缺乏维生素D的非洲血统男性的数量。此外，这些研究没有考虑维生素D水平，阳光照射，肤色以及维生素D合成和代谢途径中基因的遗传变异的相互作用。在这里，我们将提出一项前瞻性研究血清维生素D（25-OH D）水平和前列腺癌的风险，非洲裔美国人和欧洲裔美国人之间的40-79岁的男性。本研究将在五个芝加哥地区机构进行，即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、John 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在芝加哥。