Contributions of tumor molecular subtypes to prostate cancer racial disparities

肿瘤分子亚型对前列腺癌种族差异的影响

• 批准号: 10355638
• 负责人: Kevin Hughes Kensler
• 金额: $ 24.9万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10355638
• 关键词: African; African American; American; Award; Bioinformatics; Biological Factors; Biology; Cancer Biology; Cancer Prognosis; Cessation of life; Clinical Data; Clinical Management; Cluster Analysis; Complement Factor B; Computational Biology; Consensus; Dana-Farber Cancer Institute; Data; Databases; Diagnosis; Disease; Disease Management; Disease Progression; Environment; Epidemiology; Ethnic Origin; Etiology; European; Gene set enrichment analysis; Genes; Genomics; Gleason Grade for Prostate Cancer; Goals; Individual; Intervention; Knowledge; Malignant Neoplasms; Malignant neoplasm of prostate; Mediation; Mentors; Methods; Molecular; Molecular Epidemiology of Prostate Cancer; Molecular Profiling; Outcome; PTEN gene; Pathology; Phase; Phenotype; Prediction of Response to Therapy; Predictive Value; Prevalence; Prognosis; Prognostic Factor; Prognostic Marker; Progression-Free Survivals; Prostate carcinoma; Prostatic Neoplasms; Race; Radiation; Radiation therapy; Radical Prostatectomy; Research; Research Training; Resources; Retrospective cohort; Risk; Role; Socioeconomic Factors; Training; Tumor Subtype; Validation; Variant; Woman; Work; aggressive therapy; anticancer research; biological heterogeneity; cancer epidemiology; cancer health disparity; cancer subtypes; career; cohort; contextual factors; differential expression; experience; health care service utilization; improved; malignant breast neoplasm; men; molecular marker; molecular subtypes; mortality; novel; novel strategies; prognostic value; prostate cancer risk; racial disparity; risk stratification; skills; transcriptome; transcriptomics; tumor; tumor heterogeneity; tumor progression

PROJECT SUMMARY/ABSTRACT African American men (AAM) disproportionately experience the burden of prostate cancer with a mortality rate approximately 2.4-fold greater than that observed among white men in the U.S. This represents the single largest known cancer disparity by race in the U.S., and it may reflect both biologic heterogeneity in the cancers that arise in AAM, as well as differences in socioeconomic factors that influence healthcare utilization. The relative contribution of sociocontextual and biologic factors to prostate cancer disparities remains unclear. Prostate cancers are phenotypically and molecularly heterogeneous, and a better understanding of tumor subtypes by race may aid in the understanding of disease etiology and disparities. Preliminary evidence suggests that low grade tumors in AAM have a higher propensity for progression. The identification of intrinsic subtypes in other cancers, such as breast cancer, has had profound implications for our understanding of the underlying biology and clinical management of those cancers. I hypothesize that the clinical management of prostate cancer can be further optimized for AAM with further understanding of molecular tumor heterogeneity. I will leverage transcriptomic and clinical data from the Men of African Descent and Carcinoma of the Prostate Network and GenomeDx Decipher Genomic Resource Information Database™ to investigate molecular tumor subtypes with respect to prostate cancer disparities. To that end, I will: 1) characterize the PAM50 subtypes in prostate cancer by self-identified race/ethnicity and assess their prognostic value; 2) use tumor transcriptomic data to derive, validate, and characterize novel prostate cancer subtypes among AAM; 3) assemble a retrospective cohort of AAM with low-grade prostate cancer to identify molecular predictors of tumor progression. These research aims are supported by a comprehensive training plan tailored to my training goals: 1) developing an applied knowledge of advanced concepts in prostate cancer biology, epidemiology, and disparities, and 2) developing a bioinformatic and computational biology skillset. This research and training plan will provide me with the skill set to establish a career as a leader in molecular prostate cancer epidemiology and disparities research. To help me accomplish these goals, I will receive guidance from a team of experts in molecular prostate cancer research, who will help expand my knowledge of prostate cancer epidemiology, disparities, biology, pathology, clinical management, and methods for tumor molecular profiling. With the support of my mentor, Advisory Panel, and the rich training environment of Dana-Farber Cancer Institute, this award will help facilitate my transition to research independence.

项目概要/摘要 非裔美国男性 (AAM) 承受的前列腺癌负担和死亡率不成比例 大约比美国白人男性中观察到的高出 2.4 倍。 美国已知最大的种族癌症差异，它可能反映了癌症的生物学异质性 AAM 中出现的问题，以及影响医疗保健利用的社会经济因素的差异。这 社会背景和生物因素对前列腺癌差异的相对影响仍不清楚。 前列腺癌具有表型和分子异质性，更好地了解肿瘤 按种族划分的亚型可能有助于了解疾病的病因和差异。初步证据 表明 AAM 中的低级别肿瘤具有较高的进展倾向。内在的识别 其他癌症（例如乳腺癌）的亚型对我们理解癌症具有深远的影响。 这些癌症的基础生物学和临床管理。我假设临床管理 通过进一步了解分子肿瘤异质性，可以进一步优化前列腺癌的 AAM。 我将利用来自非洲人后裔和前列腺癌的转录组和临床数据 Network 和 GenomeDx Decipher Genomic Resource Information Database™ 用于研究分子肿瘤 前列腺癌差异的亚型。为此，我将： 1) 描述 PAM50 亚型的特征 前列腺癌的自我识别种族/民族并评估其预后价值； 2）使用肿瘤转录组学 用于导出、验证和表征 AAM 中新型前列腺癌亚型的数据； 3）组装一个 低级别前列腺癌 AAM 回顾性队列以确定肿瘤的分子预测因子 进展。这些研究目标得到了针对我的培训量身定制的全面培训计划的支持 目标：1）发展前列腺癌生物学、流行病学等先进概念的应用知识， 和差异，2) 开发生物信息学和计算生物学技能。本次研究和培训 计划将为我提供建立分子前列腺癌领导者职业生涯的技能 流行病学和差异研究。为了帮助我实现这些目标，我将接受团队的指导 分子前列腺癌研究专家，他们将帮助我扩展对前列腺癌的了解 流行病学、差异、生物学、病理学、临​​床管理和肿瘤分子分析方法。 在我的导师、顾问小组的支持以及丹娜—法伯癌症中心丰富的培训环境的帮助下 研究所，这个奖项将有助于促进我向独立研究的过渡。