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: 10399661
• 负责人: Kevin Hughes Kensler
• 金额: $ 19.59万
• 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/10399661
• 关键词: African American; African ancestry; 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.

项目总结/摘要 非裔美国人（AAM）不成比例地经历前列腺癌的负担， 大约是美国白色男性的2.4倍。 美国已知的最大的种族癌症差异，这可能反映了癌症的生物异质性 以及影响医疗保健利用的社会经济因素的差异。的 社会背景和生物学因素对前列腺癌差异的相对贡献仍不清楚。 前列腺癌的表型和分子异质性，更好地了解肿瘤 按种族划分的亚型可能有助于理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更高的进展倾向。内在的识别 在其他癌症中的亚型，如乳腺癌，对我们理解癌症的发病机制有着深远的影响。 这些癌症的基础生物学和临床管理。我假设， 随着对分子肿瘤异质性的进一步理解，可以进一步优化前列腺癌的AAM。 我将利用非洲裔男性和前列腺癌患者的转录组学和临床数据， Network和GenomeDx Decipher Genomic Resource Information Database™研究分子肿瘤 前列腺癌的治疗方法为此，我将：1）表征PAM 50亚型， 前列腺癌通过自我确定的种族/民族，并评估其预后价值; 2）使用肿瘤转录组学 数据以导出、验证和表征AAM中的新型前列腺癌亚型; 3）组装 低级别前列腺癌AAM的回顾性队列，以确定肿瘤的分子预测因子 进展这些研究目标是由一个全面的培训计划，为我的培训量身定制的支持 目标：1）发展前列腺癌生物学，流行病学， 和差异，以及2）开发生物信息学和计算生物学技能。这项研究和培训 该计划将为我提供一套技能，以建立一个职业生涯作为一个领导者在分子前列腺癌 流行病学和差异研究。为了帮助我实现这些目标，我将接受一个团队的指导， 分子前列腺癌研究专家，他们将帮助扩大我对前列腺癌的知识 流行病学、差异、生物学、病理学、临床管理和肿瘤分子谱分析方法。 在我的导师、顾问团和Dana-Farber Cancer丰富的培训环境的支持下， 研究所，这个奖项将有助于促进我过渡到研究独立。