Oxidative Stress, Antioxidants and Racial Disparities in Prostate Cancer

前列腺癌的氧化应激、抗氧化剂和种族差异

• 批准号: 7321269
• 负责人: CATHRYN H BOCK
• 金额: $ 13.47万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7321269
• 关键词: 8-oxoguanine; African; African American; Age; American; Antioxidants; Area; Bioinformatics; Blood specimen; Case-Control Studies; Class; Data; Disease Progression; Doctor of Philosophy; Enrollment; Etiology; European; Gene Mutation; Gene-Modified; Genes; Genetic Markers; Genetic Variation; Incidence; Individual; Institutes; Intake; Interview; K-Series Research Career Programs; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical Records; Mentorship; Mitochondria; Modeling; Morbidity - disease rate; OGG1 gene; Oxidative Stress; Oxidative Stress Pathway; Participant; Population; Population Genetics; Prevention; Questionnaires; Race; Research Personnel; Research Training; Role; SOD2 gene; Sampling; Screening procedure; Selenium/vitamin E; Superoxide Dismutase; Techniques; Testing; Training; Universities; Variant; cancer risk; experience; genetic epidemiology; glutathione peroxidase; improved; lycopene; men; metropolitan; mortality; professor; racial difference

DESCRIPTION (provided by applicant): This career development award will provide crucial training and experience in population genetics, bioinformatics, haplotyping, and tag SNP identification for Cathryn Bock, Ph.D. She is an Assistant Professor at Karmanos Cancer Institute and Wayne State University, proposing formal training and research under the mentorship of Ann Schwartz, Ph.D. and Rick Kittles, Ph.D., who have considerable expertise in these areas. In addition to attending relevant classes, seminars, and meetings, she will examine genes in the oxidative stress pathway, antioxidant intake and their potential interaction effects on racial disparities in prostate cancer incidence and progression in a sample of African American (AA) and European American men from metropolitan Detroit. Despite the considerable morbidity and mortality associated with prostate cancer, neither the etiology of the disease is not well characterized, nor are the large racial disparities. Oxidative stress has been proposed as one mechanism of prostate cancer initiation and progression, and early evidence supports this hypothesis. However, the specific role of genes in the oxidative stress pathway and their interactions with dietary and supplemental antioxidants are not yet well understood. Furthermore, it is possible that some of the racial differences in prostate cancer risk and progression may be explained by differences in genes involved in the oxidative stress pathway and their interaction with antioxidant intake. Therefore, this study will first estimate ancestry of the AA subjects using ancestry-informative markers from a previous study. Tag SNPs in three genes in the oxidative stress pathway, SOD2, OGG1, and GPX1 will then be identified. We will next assess whether variation in these genes modifies prostate cancer risk associated with intake of the antioxidants vitamin E, selenium and lycopene. Furthermore, each of these potential interactions will be examined by race and by prostate cancer aggressiveness to see if these oxidative stress pathway measures explain racial differences or disease progression. All analyses within the AA men will control for ancestry. DMA for analysis, interview, questionnaire, and medical record data will come from participants in an existing case-control study of prostate cancer in which enrollment recently was completed (PI: Benjamin A. Rybicki, Ph.D.). There are 275 AA men and 362 EA men with prostate cancer and 99 AA and 125 EA age- and race-matched men without prostate cancer enrolled in the case-control study with available data and blood samples and eligible for inclusion. This training is essential for Dr. Bock's transition to being an independent researcher in the genetic epidemiology of cancer. The identification of genetic markers for prostate cancer risk and progression, and of racial differences in the interaction of these markers with intake of antioxidants will improve screening techniques and prevention targeting efforts.

描述（由申请人提供）：该职业发展奖将为Cathryn Bock博士提供群体遗传学，生物信息学，单倍型分析和标签SNP鉴定方面的重要培训和经验。她是Karmanos癌症研究所和韦恩州立大学的助理教授，建议在Ann Schwartz博士的指导下进行正式的培训和研究。和里克·基特尔斯博士他们在这些领域有相当的专业知识。除了参加相关的课程，研讨会和会议，她将研究基因在氧化应激途径，抗氧化剂的摄入量及其潜在的相互作用对种族差异的前列腺癌的发病率和进展的样本中的非洲裔美国人（AA）和欧洲裔美国人从底特律大都市的男性。尽管与前列腺癌相关的发病率和死亡率相当高，但该病的病因尚未得到很好的表征，也没有很大的种族差异。氧化应激被认为是前列腺癌发生和发展的一种机制，早期证据支持这一假设。然而，基因在氧化应激途径中的具体作用及其与饮食和补充抗氧化剂的相互作用尚未得到很好的理解。此外，前列腺癌风险和进展的一些种族差异可能可以通过参与氧化应激途径的基因差异及其与抗氧化剂摄入的相互作用来解释。因此，本研究将首先使用先前研究中的祖先信息标记物估计AA受试者的祖先。然后将鉴定氧化应激途径中的三个基因SOD 2、OGG 1和GPX 1中的标签SNP。接下来我们将评估这些基因的变异是否会改变与摄入抗氧化剂维生素E、硒和番茄红素相关的前列腺癌风险。此外，将根据种族和前列腺癌的侵袭性来检查这些潜在的相互作用中的每一种，以了解这些氧化应激途径指标是否可以解释种族差异或疾病进展。AA男性中的所有分析都将控制血统。DMA用于分析、访谈、问卷调查和医疗记录数据，将来自一项现有的前列腺癌病例对照研究的参与者，该研究最近完成了招募（PI：Benjamin A. Rybicki，Ph.D.）。有275名AA男性和362名EA男性患有前列腺癌，99名AA和125名EA年龄和种族匹配的无前列腺癌男性入选病例对照研究，有可用的数据和血液样本，符合入选条件。这种培训对于博克博士过渡到成为癌症遗传流行病学的独立研究人员至关重要。识别前列腺癌风险和进展的遗传标记，以及这些标记与抗氧化剂摄入相互作用的种族差异，将改善筛查技术和预防靶向工作。