Molecular Epidemiology of Oxidative Stress and Related Cancers in Black Women

 描述(由申请人提供)：氧化应激被定义为“促氧化剂和抗氧化剂的失衡，伴随着氧化还原回路的破坏和大分子损伤”。慢性氧化应激被认为会增加许多癌症的风险，如乳腺癌和结直肠癌。尽管非洲裔美国人罹患和死于氧化应激相关癌症的风险增加，但在以人口为基础的氧化应激和癌症研究中，非洲裔美国人的代表性不足。氧化应激的生物标记物和营养流行病学研究尤其如此。这一职业发展奖旨在为Dash博士提供培训和研究经验，以支持他成为一名独立研究员的目标，调查少数族裔癌症的分子流行病学，包括癌症差异。拟议的培训计划包括在蛋白质组学、代谢组学、生物信息学和探索性数据分析方面的指导和课程作业，填补与少数群体研究和健康差距研究有关的研究培训空白，以及在流行病学研究中招募少数群体和收集生物标本方面的研究考虑。该提案的研究部分旨在通过(1)通过使用蛋白质组学和代谢组学技术测量一组已知的氧化应激生物标记物来表征全身氧化应激负担；(2)确定与氧化应激有关的饮食模式；以及(3)调查这些饮食模式与非裔美国女性乳腺癌和结直肠癌风险的关系。研究将分两个阶段进行。第一阶段包括使用蛋白质组和代谢组学方法测量一组6个氧化应激生物标记物，并描述非裔美国女性中没有癌症的氧化应激负担。与氧化应激生物标志物相关的饮食模式也将通过参与者在食物频率调查问卷上自我报告的饮食摄入量数据来确定。这项研究的第二阶段涉及在一项具有全国代表性的大型黑人女性队列研究中，调查第一阶段形成的与氧化应激相关的饮食模式与乳腺癌和结肠癌风险的相关性。这项研究的结果将支持更大规模和更明确的关于非裔美国女性氧化应激与癌症的研究。这项拟议的研究补充了蛋白质组学、代谢组学、生物信息学、生物统计学和少数族裔健康研究方面的培训和指导计划。获得这一奖项后，Chiranjeev Dash博士将把他以前的流行病学培训与代谢组学/蛋白质组学、生物信息学和生物统计学的高级培训结合起来，并获得少数族裔健康研究方面的经验，以建立一个独立的研究生涯，专注于癌症病因和预防中氧化应激分子流行病学的转化研究。

 DESCRIPTION (provided by applicant): Oxidative stress is defined as an "imbalance in pro-oxidants and antioxidants with associated disruption of redox circuitry and macromolecular damage". Chronic oxidative stress is believed to increase the risk of many cancers such as breast and colorectal cancers. Despite being at increased risk of developing and dying from oxidative-stress related cancers, African-Americans are under-represented in population-based studies of oxidative stress and cancer. This is especially true for biomarker-based and nutritional epidemiology studies of oxidative stress. This career development award is designed to provide training and research experience to Dr. Dash to support his goal of becoming an independent researcher investigating the molecular epidemiology of cancers among minorities including cancer disparities. Proposed training plans include mentorship and coursework in proteomics, metabolomics, bioinformatics, and exploratory data analysis, filling gaps in research training related to studies among minorities and health disparity studies, and research considerations in recruitment and bio specimen collection from minorities in epidemiologic research. The research component of the proposal aims to address the research gaps mentioned above by (1) characterizing the systemic oxidative stress burden via measurement of a panel of known biomarkers of oxidative stress using proteomics and metabolomics technologies; (2) identifying dietary patterns associated with oxidative stress; and (3) investigating the association of these dietary patterns with risk of breast and colorectal cancers among African- American women. The study will be conducted in two phases. Phase 1 involves measurement of a panel of 6 oxidative stress biomarkers using proteomic and metabolomic approaches and describing the oxidative stress burden among African-American women without cancer. Dietary patterns related to the biomarkers of oxidative stress will also be identified usin dietary intake data self-reported by participants on food frequency questionnaires. Phase 2 of the study involves investigating the association of the oxidative stress-related dietary patterns developed in Phase 1 with breast and colon cancer risk in a large, nationally-representative, cohort study of Black women. Results from the study will support larger and more definitive studies on oxidative stress and cancer among African-American women. The proposed research complements the training and mentorship plans in proteomics, metabolomics, bioinformatics, biostatistics, and minority health research. With this award Dr. Chiranjeev Dash will combine his previous training in epidemiology with advanced training in metabolomics/proteomics, bioinformatics, and biostatistics, and gain experience in conduct of minority health research to establish an independent research career focusing on translational research on the molecular epidemiology of oxidative stress in cancer causation and prevention.