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: 10688163
• 负责人: ULRIKE PETERS
• 金额: $ 64.34万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10688163
• 关键词: Address; Adoption; Affect; African American population; Age; Age of Onset; American; Asian population; Cancer Burden; Cancer Etiology; Cessation of life; Clinical; Colorectal Cancer; Communication Tools; Communities; Complex; Cost Effectiveness Analysis; Data; Decision Modeling; Development; Diagnosis; Disease; Ensure; Environmental Risk Factor; Equity; Ethics; Ethnic Origin; Ethnic Population; European; European ancestry; Evaluation; Genetic; Genetic Research; Genetic Risk; Genomics; Genotype; Incidence; Individual; Latino Population; Lead; Life Style; Mind; Minority; Minority Groups; Minority Health Research; Modality; Modeling; Not Hispanic or Latino; Online Systems; Participant; Population; Population Genetics; Population Heterogeneity; Prevention; Race; Research; Risk; Risk Factors; Science; Side; Translating; acceptability and feasibility; age effect; cancer health disparity; clinical practice; colorectal cancer risk; colorectal cancer screening; colorectal cancer treatment; commercialization; cost; cost-effectiveness evaluation; design; early onset colorectal cancer; ethnic diversity; ethnic minority; ethnic minority population; genetic approach; genetic risk factor; genome-wide; implementation science; improved; individual patient; individualized prevention; models and simulation; mortality; novel strategies; personalized intervention; personalized screening; polygenic risk score; precision medicine; preference; racial diversity; racial minority; racial minority population; racial population; recruit; risk prediction; risk prediction model; risk stratification; risk variant; screening; screening guidelines; sex; tool

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，新方法至关重要 重要的是减轻这种致命疾病的负担。精密医学持有 随着以前难以想象的基因组研究的进步，巨大的前景现在提供了广泛的 商业潜力并迅速转移到临床实践中，即使关键问题仍然存在 被解决。多基因风险评分（PRS）将共同遗传风险变体汇总为单个评分 预测疾病是一个关键例子。广泛的可访问性，基因分型成本下降以及需要考虑的需求 为了使患者的个人风险概况改善筛查，已提供了变革的机会 个性化预防。但是，大规模的PR临床采用提高了关键的道德和科学 挑战。可以说，最关键的挑战之一是当前的PR更大 由于欧元 遗传研究中心的偏见。因此，我们需要开发一个公正的PR，以预测所有人的CRC风险 主要的种族/族裔群体。但是，这只是实施的第一步，这也需要 评估最佳风险分层筛查方法和开发风险交流工具的开发 其他的。为了满足这些需求，我们将开发并验证跨种族/种族的CRC公正的PR 少数群体为风险分层的CRC筛查提供通知（AIM 1A）。我们将通过环境/ 生活方式风险评分（ERS）以考虑其他风险因素（AIM 1B），并检查差异效应 鉴于早期发作CRC的惊人增加，发作（AIM 1C）。在AIM 2A中，我们将确定最佳CRC 筛选策略鉴于AIM 1在AIM 1中定义的风险，使用我们的微观模拟建模来合并 划分年龄，性别和种族/种族以及风险因素分布的CRC发病率和死亡率差异 跨种族/族裔。在AIM 2B中，我们将评估风险分层筛查的成本效益 与当前的筛查指南相比。最后，我们将开发一个风险交流工具（AIM 3A）和 调查跨种族/种族少数群体的风险分层CRC筛查的潜在传播问题 （AIM 3B）。我们的跨学科研究团队（包括社区顾问委员会）是独特的 解决这些关键问题时1）将所有已知的种族/种族多样化的CRC汇集在一起 总计120,000多个CRC案例和对照的研究，2）在发展全面方面具有强大的专业知识 种族/种族多样性人群的遗传和环境风险评分，3）领导最多的人之一 成本效益分析的全面决策模型，该模型一直被用来通知我们 筛查指南和4）在少数群体的遗传研究实施科学方面具有专业知识。 解决所有目标对于避免在这个迅速移动的精确医学领域中的顺序科学至关重要。

项目成果

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: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 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