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
- 来源:
- 关键词:AddressAdoptionAffectAfrican American populationAgeAge of OnsetAmericanAsian populationCancer BurdenCancer EtiologyCessation of lifeClinicalColorectal CancerCommunication ToolsCommunitiesComplexCost Effectiveness AnalysisDataDecision ModelingDevelopmentDiagnosisDiseaseEnsureEnvironmental Risk FactorEquityEthicsEthnic OriginEthnic PopulationEuropeanEuropean ancestryEvaluationGeneticGenetic ResearchGenetic RiskGenomicsGenotypeIncidenceIndividualLatino PopulationLeadLife StyleMindMinorityMinority GroupsMinority Health ResearchModalityModelingNot Hispanic or LatinoOnline SystemsParticipantPopulationPopulation GeneticsPopulation HeterogeneityPreventionRaceResearchRiskRisk FactorsScienceSideTranslatingacceptability and feasibilityage effectcancer health disparityclinical practicecolorectal cancer riskcolorectal cancer screeningcolorectal cancer treatmentcommercializationcostcost-effectiveness evaluationdesignearly onset colorectal cancerethnic diversityethnic minorityethnic minority populationgenetic approachgenetic risk factorgenome-wideimplementation scienceimprovedindividual patientindividualized preventionmodels and simulationmortalitynovel strategiespersonalized interventionpersonalized screeningpolygenic risk scoreprecision medicinepreferenceracial diversityracial minorityracial minority populationracial populationrecruitrisk predictionrisk prediction modelrisk stratificationrisk variantscreeningscreening guidelinessextool
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.
项目总结/摘要
由于结直肠癌(CRC)仍然是癌症死亡的主要原因之一,因此新方法至关重要
我们必须在减少这一致命疾病的负担方面取得重大进展。精准医疗
巨大的希望,因为基因组研究的进步,以前是不可想象的,现在提供了巨大的
商业潜力,并迅速进入临床实践,即使关键问题仍然存在,
被解决。多基因风险评分(PRS),将常见的遗传风险变异汇总为单个评分,
预测疾病是一个重要的例子。广泛的可及性,降低基因分型成本,以及需要考虑
为患者的个体风险状况,以改善筛查提供了变革的机会,
个性化预防。然而,PRS的大规模临床采用提出了关键的伦理和科学问题,
挑战可以说,最关键的挑战之一是,目前的减贫战略大大超过了
与其他人群相比,欧洲血统的个体有效预测风险,
基因研究中的中心偏向因此,我们需要制定一个无偏见的PRS,预测CRC风险的所有
主要种族/民族群体。然而,这只是实施的第一步,还需要
评估最佳风险分层筛选方法,开发风险沟通工具,
他人为了满足这些需求,我们将制定并验证跨种族/种族的CRC无偏见PRS。
少数群体告知风险分层CRC筛查(目标1a)。我们会在生产者责任计划中加入环保/
生活方式风险评分(ERS),以解释其他风险因素(目标1b),并检查年龄的差异效应,
发病(目标1c),因为早发性CRC的惊人增加。在目标2a中,我们将确定最佳CRC
在目标1中定义的个体风险下,使用我们的微观模拟模型,
不同年龄、性别和人种/种族的CRC发病率和死亡率差异,以及风险因素分布
种族/民族群体。在目标2b中,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,我们将开发风险沟通工具(目标3a),
调查风险分层CRC筛查在少数民族/种族群体中的潜在传播问题
(Aim 3 b)。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,
解决这些关键问题,因为我们1)将所有已知的种族/民族多样化的CRC聚集在一起,
研究总计超过120,000例CRC病例和对照,2)在开发全面的
在种族/民族多样化的人群中的遗传和环境风险评分,3)导致最
成本效益分析的综合决策模型,该模型一直被用于告知我们
筛选准则和4)在少数群体遗传研究的实施科学方面具有专门知识。
在这个快速发展的精准医学领域,解决所有目标对于避免顺序科学至关重要。
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。
- DOI:10.1016/j.cgh.2023.03.003
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:vandenPuttelaar,Rosita;Meester,ReinierGS;Peterse,ElisabethFP;Zauber,AnnG;Zheng,Jiayin;Hayes,RichardB;Su,Yu-Ru;Lee,JeffreyK;Thomas,Minta;Sakoda,LoriC;Li,Yi;Corley,DouglasA;Peters,Ulrike;Hsu,Li;Lansdorp-Vogelaar,Iris
- 通讯作者:Lansdorp-Vogelaar,Iris
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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:
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:
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:
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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