Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications

氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响

基本信息

  • 批准号:
    10312770
  • 负责人:
  • 金额:
    $ 67.79万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-12-01 至 2025-11-30
  • 项目状态:
    未结题

项目摘要

SUMMARY Conventional wisdom says that antioxidants should lower cancer risk by neutralizing cell- damaging, cancer-causing oxidative stress. However, despite the compelling biochemical evidence that ties oxidative damage to carcinogenesis for in vitro systems, almost all large randomized clinical trials have shown that antioxidant supplementation provides no clear benefit and even increases cancer risk. These disappointing and seemingly contradictory results have puzzled the public and researchers for decades. Even more controversial is whether antioxidant supplementation is safe and effective for cancer survivors. An estimated 15.5 million Americans in 2016 were cancer survivors, and up to 81% of them used antioxidant supplements to promote healing. However, we do not understand whether and to what extent post-treatment oxidative stress is associated with cancer prognosis. We recently conducted a molecular epidemiological study of colorectal cancer (CRC). We found the first piece of evidence in humans that the association between oxidative stress and CRC risk was bidirectional, with both beneficial and deleterious effects. Moreover, these bidirectional effects were time-dependent. Specifically, in earlier phases of cancer development, high oxidative stress was associated with increased risk of CRC, whereas in later phases, it was associated with decreased risk. Correspondingly, we found that the association between antioxidant intake and CRC risk was also time- dependent and varied by baseline oxidative stress. In the pilot study, we found that among patients with more advanced cancer, their systemic levels of oxidative stress were actually lower. Furthermore, cancer patients with higher post-treatment levels of oxidative stress had odds of living longer, after comprehensively adjusting for clinical parameters. In this proposed study, we will conduct a large case-cohort study, building upon three Asian and European cohorts to determine whether our novel findings—the time-dependent and bidirectional effects of oxidative stress and antioxidants on CRC, first observed in Chinese women (discovery phase)—can be replicated in both sexes and in different ethnic populations (replication phase). Comprehensive assessments of oxidative stress in pre-diagnostic urine samples will be performed. We will also conduct a follow-up study of CRC cases from whom both pre-diagnostic and post-treatment urine samples have been collected. We will examine whether higher levels of systemic post-treatment oxidative stress are associated with better CRC survival, while comprehensively accounting for pre-diagnostic oxidative stress and other clinical parameters. We expect that this study, with its focus on the time-dependent and bidirectional association between oxidative stress and CRC, will provide novel insights into the role of oxidative stress in carcinogenesis, the first evidence linking oxidative stress and clinical outcomes of CRC, and much needed information for identification of population subsets for chemoprevention. Thus, this study will have high translational potential to lead to tailored strategies for CRC prevention and patient care.
总结

项目成果

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Qingxia Chen其他文献

Qingxia Chen的其他文献

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{{ truncateString('Qingxia Chen', 18)}}的其他基金

DARSaW: Developing, Assessing, and Refining Synthetic Sampling Weights to Improve Generalizability of the All of Us Research Program Data
DARSaW:开发、评估和细化合成采样权重,以提高我们所有人研究计划数据的普遍性
  • 批准号:
    10796237
  • 财政年份:
    2023
  • 资助金额:
    $ 67.79万
  • 项目类别:
Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
  • 批准号:
    10520027
  • 财政年份:
    2019
  • 资助金额:
    $ 67.79万
  • 项目类别:
Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
  • 批准号:
    9887609
  • 财政年份:
    2019
  • 资助金额:
    $ 67.79万
  • 项目类别:
Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
  • 批准号:
    10063979
  • 财政年份:
    2019
  • 资助金额:
    $ 67.79万
  • 项目类别:
A New Approach to Correct Verification Bias Using Auxiliary Information
使用辅助信息纠正验证偏差的新方法
  • 批准号:
    8048932
  • 财政年份:
    2010
  • 资助金额:
    $ 67.79万
  • 项目类别:
A New Approach to Correct Verification Bias Using Auxiliary Information
使用辅助信息纠正验证偏差的新方法
  • 批准号:
    8207859
  • 财政年份:
    2010
  • 资助金额:
    $ 67.79万
  • 项目类别:

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