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

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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.