Comparative Effectiveness of Genomics Assay for Active Surveillance Failure Prediction in African American Men: the impact of genetic ancestry and socioeconomic status.

基因组学测定对非裔美国男性主动监测失败预测的比较有效性：遗传血统和社会经济地位的影响。

基本信息

批准号：
9199234
负责人：
Adam Bryant Murphy
金额：
$ 17.4万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2018-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Prostate Cancer (PCa) is the most common malignancy in men but overtreatment is a major public health concern. To address this, Genomic Health Inc. in collaboration with academic and military hospitals validated a 17-gene relative expression assay to predict the probability of adverse pathologic features at the time of radical prostatectomy to improve the safety of active surveillance. Their Oncotype DX (ODX) assay improves the prognostic accuracy beyond standard clinical parameters at the time of biopsy. The ODX GPS is scaled from 0-100 and increases the number of men deemed eligible for active surveillance by decreasing the pre-test probability of adverse pathology and allows patients and providers to confidently elect active surveillance to avoid upfront treatment morbidity. ODX has been validated in largely European American (EA) populations but has yet to be adequately assessed in high-risk African American (AA) men. Our overarching hypothesis is that the prognostic accuracy of Oncotype DX varies by race and by socioeconomic status and genetic ancestry among AAs. This is significant since AAs have the highest risk of PCa and PCa mortality and are more likely to harbor adverse pathology in their prostate despite being eligible for active surveillance by clinical parameters. Risk of aggressive PCa varies across studies in AA men based on socioeconomic factors including insurance, education and income. Moreover, gene expression varies significantly between AA and EA prostate tumors. Given this, ODX can be dangerous for AAs if prediction performance is poorer or differs significantly between AAs and EAs or between subpopulations of AAs with clinically localized prostate cancer (CLPCa). To assess the prediction performance of ODX in AAs with CLPCa, we propose the following Specific Aims: (1) to compare the effectiveness of the ODX GPS as a predictor of adverse pathology in archived specimen from 100 AA and 50 EA men with CLPCa; (2) to compare the prediction performance of the GPS for adverse pathology in archived specimen from 150 AAs with CLPCa from divergent socio-demographic (income, education, insurance status) backgrounds; (3) to assess for variation in GPS prediction performance in 100 previously recruited AAs with CLPCa by degree of genetic European or African ancestry. Should this comparative effectiveness study reveal variations in prediction performance by race, socioeconomic status or genetic ancestry, a calibrated GPS score could be provided. Alternatively, if the ODX assay inadequately measures risk of adverse pathology we prevent its use in men of African ancestry. In either scenario we improve the safety of active surveillance for a high-risk PCa population.

描述（由适用提供）：前列腺癌（PCA）是男性最常见的恶性肿瘤，但过度治疗是一个主要的公共卫生问题。为了解决这个问题，基因组健康公司与学术和军事医院合作验证了17基因相对表达测定法，以预测根治性前列腺切除术时不良病理特征的可能性，以提高主动监视的安全性。他们的ODY型DX（ODX）测定ODX已在大型欧美人群中得到验证，但尚未在高风险的非裔美国人（AA）男性中进行充分评估。我们的总体假设是，AAS中的种族和社会经济地位和遗传血统的Oncotype DX变化的预后准确性。这很重要，因为AAS具有PCA和PCA死亡率的最高风险，并且尽管有资格通过临床参数进行主动监测，但仍可能在前列腺中具有不良病理。基于保险，教育和收入在内的社会经济因素，在AA男性研究中有侵略性PCA变化的风险。此外，基因表达在AAS和EA前列腺肿瘤之间显着。鉴于此，如果AAS和EAS之间的预测性能较差或明显不同，则ODX对于AAS可能是危险的，或者在患有临床局部局部前列腺癌（CLPCA）的AAS亚群之间存在显着差异。为了评估使用CLPCA在AAS中ODX的预测性能，我们提出了以下特定目的：（1）将ODX GPS作为不良病理学的有效性比较了100个AA和50名EA患者CLPCA的不良病理的预测因子；（2）比较在150 AA的存档标本中GP对不良病理的预测性能与来自不同社会人口统计学（收入，教育，保险状态）背景的CLPCA的预测性能；（3）评估以前100个以前招募AAS的GPS预测性能的变化，该AAS通过遗传欧洲或非洲血统的程度与CLPCA一起招募了AAS。如果这项比较有效性研究揭示了种族，社会经济地位或遗传血统的预测绩效差异，则可以提供校准的GPS评分。另外，如果ODX测定法衡量不良病理的风险，我们会阻止其在非洲血统中的使用。在两种情况下，我们都提高了高风险PCA人群的主动监视安全性。