Investigations of Black Ancestry on Pancreatic Cancer Tumor Biology for US-related Cancer Health Disparities

黑人血统对胰腺癌肿瘤生物学与美国相关癌症健康差异的调查

基本信息

批准号：
10166025
负责人：
FOLAKEMI T ODEDINA
金额：
$ 19.24万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-17 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10166025
关键词：
Address Administrative Supplement Africa African African American American Applications Grants Area Automobile Driving Award Biological California Cancer Center Caribbean region Clinical Data Colorectal Cancer DNA Sequence DNA Sequence Alteration Data Disease Early Diagnosis Education Epidemiology Florida Foundations Funding Gene Mutation Genetic Genomics Goals Health Heterogeneity Hispanics Incidence Infrastructure Investigation Investments Knowledge Latino Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Malignant neoplasm of pancreas Malignant neoplasm of prostate Malignant neoplasm of urinary bladder Minority Minority Groups Molecular Profiling Mutation NCI Center for Cancer Research National Cancer Institute Nigeria Nigerian Not Hispanic or Latino Organ Outcome Pancreatic Ductal Adenocarcinoma Pathway interactions Patients Population Regimen Research Research Personnel Research Project Grants Resource Sharing Resources Saliva Scientist Serum Solid Somatic Mutation Tissue Model Tissues Training Translational Research Treatment Efficacy Tumor Biology Tumor-Derived United States National Institutes of Health Universities anticancer research base biobank cancer health disparity cancer type career epidemiology study ethnic diversity exome sequencing gemcitabine health disparity health equity improved innovation interest malignant breast neoplasm mortality new therapeutic target next generation pancreatic neoplasm parent grant patient population prognostic value programs response treatment response tumor tumor growth

项目摘要

ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT- CA-20-032. The applicant parent grant is the Florida-California Cancer Research, Education & Engagement (CaRE2) Health Equity Center at University of Florida (MPIs: Odedina and Wilkie). The CaRE2 Health Equity Center was established in 2018 through funding from the NIH/National Cancer Institute (NCI) collaborative partnership among University of Florida (UF), Florida A&M University and University of Southern California (U54CA233444, U54CA233396, U54CA233465). The long-term goals of the CaRE2 center are to reduce cancer disparities in Blacks and Latinos, to train and increase the pool of underrepresented Black and Latino scientists conducting health disparity research, to increase research capacity at Florida A&M University, and to increase cancer disparity research at UF and University of Southern California. The main scientific focus of the center is translational disparities research among heterogeneous minority populations focusing on cancers known for high mortality. We are coalescing expertise, infrastructure and sharing resources in support of six (6) innovative translational research projects focused on understanding the biological basis of disparities in Black and Latino populations, capturing the wide heterogeneity within these two groups, with two foundational projects focusing on pancreas cancer (one full, one pilot) and one full project focusing on prostate cancer. This supplement award application focuses on Pancreatic Ductal Adenocarcinoma (PDAC) to: (1) expand our understanding of the biological basis of disparities in ethnically diverse Black populations by comparing US Blacks to their ancestral populations in Nigeria, Africa; and (2) stimulate global cancer health disparities research in Africa through genomic and epidemiological study of PDAC in Nigerian patients. The primary aim is to explore if there are genomic differences between US Blacks and their ancestral populations in Nigeria relative to PDAC. A secondary aim is to characterize and compare the burden of PDAC among US Blacks and Nigerians. Unique gene mutations have been identified in PDAC from non-Hispanic Black Americans. An ongoing study by our team discovered 22 new somatic mutations in US Black tumors and these mutations were found to have prognostic value in other solid organ tumors. However, we are not aware of any PDAC genomic study comparing US Blacks to Nigerians. Comparison of genetic mutations of US Blacks and Nigerians will improve knowledge of the pathways to PDAC where incidence rates may be partially explained by genetic differences. Whole-exome sequencing is a powerful means by which to sequence DNA derived from tumor to identify somatic mutations. The addition of ancestral data will allow for comparison of genetic alterations of US Blacks and one of their ancestral populations, Nigerians. It is unclear if there may be a similarity in the genetic drivers of PDAC in both US Blacks and Nigerians or if there are differences in tumor genetics that may account for disparate outcomes between US Blacks and Nigerians. Investigating this important area may identify means of early detection and novel therapeutic targets in the treatment of PDAC as the genomic alterations driving tumor growth in minority groups may be fundamentally different from those arising in Whites. The study team is led by Dr. Jose Trevino (a clinician scientist whose research career is dedicated to understanding pancreatic cancer amongst a diverse patient population) and Dr. Folakemi Odedina (a global cancer health disparities scientist who leads an NIH/NCI Epidemiology and Genomics Research Program - approved cancer consortium with over 100 investigators in Africa). Within the last 15 years, Dr. Odedina’s Prostate Cancer Transatlantic Consortium (CaPTC) has been leveraged to stimulate global cancer health disparities research in the areas of breast cancer, bladder cancer, colorectal cancer, pancreatic cancer, ovarian cancer and lung cancer. In addition to building on the resources of the NIH/NCI CaRE2 U54 Center, we are leveraging the existing NIH/NCI investment in the CaPTC for this supplement. Through the CaPTC, the CaRE2 Center Tissue Modeling Core (TMC) is building a robust global biobank for different types of cancer, including PDAC. Using the leveraged funding provided by the UF Health Cancer Center, the CaRE2 TMC has a robust “next-generation biobank” that includes clinical data, tissues (pancreatic tumor and “normal” adjacent tissue) and biofluids (serum, saliva) of PDAC patients from the US and Nigeria.

抽象的本申请是为了响应被确定为 NOT- 的特殊利益通知 (NOSI) 而提交的 CA-20-032 申请人家长补助金是佛罗里达州-加利福尼亚州癌症研究、教育和参与组织。 (CaRE2) 佛罗里达大学健康公平中心（MPI：Odedina 和 Wilkie）。该中心成立于 2018 年，由 NIH/国家癌症研究所 (NCI) 合作资助佛罗里达大学 (UF)、佛罗里达农工大学和南加州大学之间的合作伙伴关系（U54CA233444、U54CA233396、U54CA233465）CaRE2 中心的长期目标是减少癌症。黑人和拉丁裔之间的差异，以培训和增加代表性不足的黑人和拉丁裔科学家的数量开展健康差异研究，提高佛罗里达农工大学的研究能力，并提高佛罗里达大学和南加州大学的癌症差异研究该中心的主要科学重点是。异质少数群体之间的转化差异研究，重点关注以高发病率闻名的癌症我们正在整合专业知识、基础设施并共享资源，以支持六 (6) 项创新。转化研究项目的重点是了解黑人和拉丁裔差异的生物学基础人口，捕捉这两个群体内的广泛异质性，两个基础项目侧重于关于胰腺癌的项目（一项完整项目，一项试点项目）和一项针对前列腺癌的完整项目。该补充奖励申请重点关注胰腺导管腺癌 (PDAC)，以：(1) 扩展通过比较美国，我们对不同种族黑人人口差异的生物学基础的理解非洲尼日利亚的黑人及其祖先人口；(2) 加剧全球癌症健康差异；通过尼日利亚患者 PDAC 的基因组和流行病学研究在非洲开展研究。是探索美国黑人与其尼日利亚祖先群体之间是否存在基因组差异相对于 PDAC 的第二个目标是描述和比较美国黑人和黑人中 PDAC 的负担。尼日利亚人在非西班牙裔美国黑人的 PDAC 中发现了独特的基因突变。我们团队正在进行的研究在美国黑人肿瘤中发现了 22 个新的体细胞突变，这些突变是发现对其他实体器官肿瘤具有预后价值然而，我们不知道任何 PDAC 基因组。比较美国黑人和尼日利亚人的研究将比较美国黑人和尼日利亚人的基因突变。提高对 PDAC 途径的了解，其中发病率可能部分由遗传因素解释全外显子组测序是对源自肿瘤的 DNA 进行测序的有力手段。识别体细胞突变。添加祖先数据将允许比较美国的基因改变。黑人和他们的祖先之一尼日利亚人的基因是否相似尚不清楚。美国黑人和尼日利亚人中 PDAC 的驱动因素，或者肿瘤遗传学是否存在差异针对美国黑人和尼日利亚人之间不同的结果，调查这一重要领域可能会找到方法。基因组改变驱动 PDAC 治疗的早期检测和新治疗靶点少数族裔的肿瘤生长可能与白人的肿瘤生长有根本不同。该研究小组由 Jose Trevino 博士（一位临床科学家，其研究生涯致力于了解不同患者群体中的胰腺癌）和 Folakemi Odedina 博士（全球领导 NIH/NCI 流行病学和基因组学研究项目的癌症健康差异科学家 - 在过去 15 年里，Odedina 博士的癌症联盟获得了批准，该联盟在非洲拥有 100 多名研究人员。前列腺癌跨大西洋联盟 (CaPTC) 已被用来促进全球癌症健康乳腺癌、膀胱癌、结直肠癌、胰腺癌、卵巢癌领域的差异研究除了利用 NIH/NCI CaRE2 U54 中心的资源外，我们还致力于癌症和肺癌的研究。利用 NIH/NCI 对 CaPTC 的现有投资来提供此补充。中心组织建模核心 (TMC) 正在为不同类型的癌症建立一个强大的全球生物库，包括利用佛罗里达大学健康癌症中心提供的杠杆资金，CaRE2 TMC 拥有强大的实力。 “下一代生物库”，包括临床数据、组织（胰腺肿瘤和“正常”邻近组织）和来自美国和尼日利亚的 PDAC 患者的生物体液（血清、唾液）。