Advancing equity in colorectal cancer genetic risk prediction through expansion of racial/ethnic minority representation

通过扩大种族/族裔少数群体代表性,促进结直肠癌遗传风险预测的公平性

基本信息

  • 批准号:
    10688163
  • 负责人:
  • 金额:
    $ 64.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

Project Summary / Abstract As colorectal cancer (CRC) remains one of the leading causes of cancer death new approaches are of vital importance to make critical inroads in reducing the burden of this lethal disease. Precision medicine holds enormous promise as advances in genomic research that were previously unimaginable now offer vast commercial potential and are rapidly being moved into clinical practice, even though critical questions remain to be addressed. Polygenic risk scores (PRS) that aggregate common genetic risk variants into a single score to predict disease are a key example. Broad accessibility, plummeting genotyping costs, and the need to account for the patient's individual risk profile to improve screening have provided transformative opportunities in personalized prevention. However, wide-scale clinical adoption of PRS raises key ethical and scientific challenges. Arguably one of the most critical challenge is the fact that current PRS are substantially more effective in predicting risk in individuals of European ancestry compared with other populations due to the Euro- centric bias in genetic research. Accordingly, we need to develop an unbiased PRS that predicts CRC risk in all major racial/ethnic groups. However, this is only the first step towards implementation, which also requires the evaluation of the optimal risk-stratified screening approach and development of risk communication tool among others. To address these needs, we will develop and validate an unbiased PRS for CRC across ethnic/racial minority groups to inform risk-stratified CRC screening (Aim 1a). We will augment the PRS with an environmental/ lifestyle risk score (ERS) to account for other risk factors (Aim 1b) and examine differential effects by age of onset (Aim 1c), given the alarming increase of early onset CRC. In Aim 2a we will determine the optimal CRC screening strategy given an individual's risk defined in Aim 1 using our microsimulation modeling by incorporating differences in CRC incidence and mortality rates by age, sex and race/ethnicity, and in risk factor distributions across racial/ethnic groups. In Aim 2b we will evaluate the cost-effectiveness of risk stratified screening compared with current screening guidelines. Finally, we will develop a risk communication tool (Aim 3a) and investigate potential dissemination issues of risk-stratified CRC screening across ethnic/racial minority groups (Aim 3b). Our trans-disciplinary research team, which includes a community advisory board, is uniquely set up to address these critical questions as we 1) have brought together all known racially/ethnically diverse CRC studies totaling to over 120,000 CRC cases and controls, 2) have strong expertise in developing comprehensive genetic and environmental risk scores in racially/ethnically diverse populations, 3) lead one of the most comprehensive decision models for cost-effectiveness analysis which has consistently been used to inform US screening guidelines and 4) have expertise in implementation science for genetic research in minorities. Addressing all aims is critical to avoid a sequential science in this rapidly moving field of precision medicine.
项目摘要/摘要 由于结直肠癌(CRC)仍然是癌症死亡的主要原因之一,新的治疗方法至关重要。 在减轻这一致命疾病的负担方面取得重大进展具有重要意义。精准医学支撑 随着基因组研究的进步,以前不可想象的巨大前景现在提供了巨大的 商业潜力,并正在迅速进入临床实践,尽管关键问题仍然是 被称呼为。多基因风险分数(PR),将常见的遗传风险变量聚合到单个分数中,以 预测疾病是一个关键的例子。广泛的可及性,基因分型成本的直线下降,以及需要考虑 对于患者的个人风险概况来说,改善筛查提供了变革性的机会 个性化预防。然而,PrS的广泛临床采用提高了关键的伦理和科学 挑战。可以说,最关键的挑战之一是,当前的PR大大超过了 与其他人群相比,欧洲血统的个人在预测由于欧元- 遗传学研究中的中心偏向。因此,我们需要开发一种公正的预测结直肠癌风险的方法。 主要种族/民族群体。然而,这只是实现的第一步,这还需要 最佳风险分层筛选方法的评价及风险沟通工具的开发 其他。为了满足这些需求,我们将为儿童权利委员会制定和验证一项不带偏见的跨民族/种族责任计划 向少数群体通报风险分层的儿童疾病筛查(目标1a)。我们将通过环境保护/ 生活方式风险评分(ERS),以考虑其他风险因素(目标1b),并检查不同年龄的差异影响 初发(目标1c),鉴于早发性CRC的增加令人震惊。在目标2a中,我们将确定最佳CRC 给出目标1中定义的个人风险的筛选策略,使用我们的微观模拟建模,通过合并 不同年龄、性别和种族/民族的结直肠癌发病率和死亡率以及危险因素分布的差异 跨种族/民族群体。在目标2b,我们将评估风险分层筛查的成本效益。 与目前的筛查指南相比。最后,我们将开发一个风险沟通工具(目标3a)和 调查风险分层结直肠癌筛查在少数民族人群中的潜在传播问题 (目标3b)。我们的跨学科研究团队,其中包括一个社区咨询委员会,是独一无二的 为了解决这些关键问题,我们1)将所有已知的不同种族/民族的CRC聚集在一起 总计超过120,000例结直肠癌病例和对照的研究;2)在制定全面的 在种族/民族多元化人群中的遗传和环境风险得分,3)领先于 用于成本效益分析的综合决策模型,一直被用于向美国提供信息 筛查指南和4)在少数群体基因研究的实施科学方面具有专门知识。 解决所有目标是关键,以避免在这个快速发展的精确医学领域出现顺序科学。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Risk-Stratified Screening for Colorectal Cancer Using Genetic and Environmental Risk Factors: A Cost-Effectiveness Analysis Based on Real-World Data.
利用遗传和环境风险因素对结直肠癌进行风险分层筛查:基于真实世界数据的成本效益分析。
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ULRIKE PETERS其他文献

ULRIKE PETERS的其他文献

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{{ truncateString('ULRIKE PETERS', 18)}}的其他基金

Project 2: Racial/ethnic differences, impact on tumor microenvironment and mortality
项目2:种族/民族差异、对肿瘤微环境和死亡率的影响
  • 批准号:
    10044050
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Developmental Research Program
发展研究计划
  • 批准号:
    10244967
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Advancing equity in colorectal cancer genetic risk prediction through expansion of racial/ethnic minority representation
通过扩大种族/族裔少数群体代表性,促进结直肠癌遗传风险预测的公平性
  • 批准号:
    10180920
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10466936
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Advancing equity in colorectal cancer genetic risk prediction through expansion of racial/ethnic minority representation
通过扩大种族/族裔少数群体代表性,促进结直肠癌遗传风险预测的公平性
  • 批准号:
    10433925
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10601405
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10044048
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Developmental Research Program
发展研究计划
  • 批准号:
    10044052
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Developmental Research Program
发展研究计划
  • 批准号:
    10601409
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:
Project 2: Racial/ethnic differences, impact on tumor microenvironment and mortality
项目2:种族/民族差异、对肿瘤微环境和死亡率的影响
  • 批准号:
    10466939
  • 财政年份:
    2020
  • 资助金额:
    $ 64.34万
  • 项目类别:

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