Oxidative Stress, Antioxidants and Racial Disparities in Prostate Cancer

描述（由申请人提供）：该职业发展奖将为凯瑟琳·博克博士提供在群体遗传学、生物信息学、单倍型和标签SNP鉴定方面的重要培训和经验。她是卡尔马诺斯癌症研究所和韦恩州立大学的助理教授，建议在Ann Schwartz博士和Rick Kittles博士的指导下进行正式培训和研究，他们在这些领域具有相当的专业知识。除了参加相关的课程、研讨会和会议外，她还将研究氧化应激途径中的基因、抗氧化剂的摄入及其对来自底特律大都会的非裔美国人和欧裔美国人前列腺癌发病率和进展的种族差异的潜在相互作用。尽管与前列腺癌相关的发病率和死亡率相当高，但该病的病因和巨大的种族差异都没有得到很好的描述。氧化应激被认为是前列腺癌发生和发展的机制之一，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膳食和补充抗氧化剂的相互作用尚不清楚。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及其与抗氧化剂摄入相互作用的基因差异来解释。因此，本研究将首先使用前人研究中的祖先信息标记来估计AA受试者的祖先。随后将鉴定氧化应激途径中SOD2、OGG1和GPX1三个基因的标签snp。接下来我们将评估这些基因的变异是否会改变与抗氧化剂维生素E、硒和番茄红素摄入有关的前列腺癌风险。此外，这些潜在的相互作用将通过种族和前列腺癌的侵袭性来检查，看看这些氧化应激途径是否解释了种族差异或疾病进展。所有AA成员的分析都将控制他们的祖先。DMA的分析、访谈、问卷调查和医疗记录数据将来自最近完成登记的前列腺癌病例对照研究的参与者（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男性和125名EA男性年龄和种族匹配，但没有前列腺癌，纳入了病例对照研究，有可用的数据和血液样本，符合纳入条件。这种培训对于博克博士成为癌症遗传流行病学的独立研究人员至关重要。确定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之间相互作用的种族差异，将改善筛查技术和预防目标。

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.