R01CA254951

Germline and Somatic Genomic Studies in CLL Minorities - African Americans are significantly underrepresented in cancer research. Although there have been recent efforts toward more inclusion of African Americans in cancer research, substantial work is still needed.

Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in the U.S., with approximately 21,000 new cases diagnosed each year. Despite significant developments in therapeutic interventions and subsequent improvements in outcome, CLL is still incurable.

Initial findings have demonstrated differences in molecular and clinical characteristics of CLL patients between African Americans and Caucasians. African American CLL patients have a younger age of onset, a more aggressive disease at diagnosis, shorter median time to therapy initiation, and reduced overall survival compared to Caucasians, even after controlling for therapy. This suggests that other factors may exist that are driving this disparity.

Despite these differences across these two populations, little is known about the relationship between genomics, race, and CLL pathogenesis. To date, the genetic landscape of CLL has been considerably scrutinized but only among individuals of European descent.

The goal of this application is to directly evaluate the genetic basis of CLL among African Americans, with the overall hypothesis that genomic heterogeneity exists between African American and Caucasian populations that may drive, in part, the disparity in risk, morbidity, and mortality in CLL.

To test this hypothesis, we will leverage our extensive experience in CLL and apply it to our collection of African American individuals with CLL. In Aim 1, we will perform a multi-omic (genomic, transcriptomic, and epigenomic) study in African American CLL individuals and compare the findings with publicly available sequencing data from Caucasian CLL individuals. With these data, we will be able to characterize the tumor heterogeneity across these two populations and identify novel somatic findings.

In Aim 2, we will evaluate the known CLL susceptibility loci identified through genome-wide association studies (GWAS) of Caucasians in African American CLL cases and controls. This will provide insight into the differential risk of the index variants and any other variants in the loci across African American and Caucasian populations.

Finally, in Aim 3, we will evaluate the generalizability of our recent findings that the genomic summary measure, the tumor mutational load, defined as the number of recurrently mutated CLL driver genes, is prognostic in African American CLLs.

The knowledge gained from this application may provide novel insight into the biological differences in leukemogenesis across these two racial groups, as well as provide understanding of the generalizability of the inherited and somatic genetic findings found in Caucasian CLL to African American CLL. Together, these results may improve risk stratification and prognostication among African American CLL cases, and ultimately, they may provide new insights into possible avenues to reduce health disparity in CLL.

Mayo Clinic

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Rochester, Minnesota 559050001 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 382% from $677,092 to $3,266,846.