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

• 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
• 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

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.

摘要 本申请是为了回应特别利益通知（NOSI）而提交的，该通知被确定为不- CA-20-032申请人父母补助金是佛罗里达州-加利福尼亚州癌症研究，教育和参与 （CaRE 2）健康公平中心在佛罗里达大学（MPI：Odedina和威尔基）。CARE 2健康公平 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伙伴关系 （U54CA233444、U54CA233396、U54CA233465）。CARE 2中心的长期目标是减少癌症 黑人和拉丁美洲人的差异，以培训和增加代表性不足的黑人和拉丁美洲科学家的人才库 进行健康差异研究，以提高佛罗里达A&M大学的研究能力，并增加 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 异质性少数群体之间的转化差异研究，重点关注以高 mortality.我们正在整合专业知识，基础设施和共享资源，以支持六（6）个创新 翻译研究项目侧重于了解黑人和拉丁美洲人差异的生物学基础 人口，捕捉这两个群体内的广泛异质性，两个基础项目重点 胰腺癌（一个完整的，一个试点）和一个完整的项目集中在前列腺癌。 该补充奖申请重点关注胰腺导管腺癌（PDAC）：（1）扩大 我们通过比较美国和美国， 非洲尼日利亚的黑人祖先;（2）刺激全球癌症健康差距 通过对尼日利亚患者进行PDAC的基因组和流行病学研究，在非洲进行研究。主要目的 是探索美国黑人和他们在尼日利亚的祖先群体之间是否存在基因差异 相对于PDAC。第二个目的是描述和比较美国黑人和 埃塞俄比亚人。在非西班牙裔美国黑人的PDAC中发现了独特的基因突变。一个 我们团队正在进行的一项研究发现，在美国黑人肿瘤中有22种新的体细胞突变，这些突变是 发现在其他实体器官肿瘤中具有预后价值。然而，我们不知道任何PDAC基因组 美国黑人与美国黑人的比较研究。美国黑人和印第安人的基因突变比较将 提高对PDAC途径的认识，其中发病率可能部分由遗传因素解释 差异全外显子组测序是一种强有力的手段，通过该手段对来源于肿瘤的DNA进行测序， 识别体细胞突变。增加祖先数据将允许比较美国的遗传改变， 黑人和他们的祖先之一，埃塞俄比亚人。目前还不清楚是否有可能在遗传相似性， 在美国黑人和哥伦比亚人中PDAC的驱动因素，或者是否存在肿瘤遗传学差异， 美国黑人和黑人之间的不同结果。对这一重要领域进行调查， 早期检测和新的治疗靶点在治疗PDAC作为基因组改变驱动 少数群体中的肿瘤生长可能与白人中产生的肿瘤生长根本不同。 该研究小组由Jose Trevino博士（临床科学家，其研究生涯致力于 了解不同患者人群中的胰腺癌）和Folakemi Odedina博士（全球 癌症健康差异科学家，领导NIH/NCI流行病学和基因组学研究计划， 在非洲有超过100名研究人员的癌症联盟）。在过去的15年里，Odedina博士 前列腺癌跨大西洋联盟（CaPTC）已被用来刺激全球癌症健康 乳腺癌、膀胱癌、结肠直肠癌、胰腺癌、卵巢癌、乳腺癌、 癌症和肺癌。除了利用NIH/NCI CaRE 2 U 54中心的资源外，我们还 利用现有的NIH/NCI在CaPTC中的投资来获得这种补充。通过CaPTC，CaRE 2 组织建模中心（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 PDAC。使用UF健康癌症中心提供的杠杆资金，CaRE 2 TMC有一个强大的 “下一代生物库”，包括临床数据、组织（胰腺肿瘤和“正常”相邻组织）和 来自美国和尼日利亚的PDAC患者的生物流体（血清、唾液）。