Biological Determinants of Kidney Cancer Health Disparities
Abstract
Background: Kidney cancer ranks as a top 10 leading site of new cancer cases (~64,000), killing ~15,000 people in the U.S. each year. Renal cell carcinoma (RCC) is the most common type of kidney cancer (~90% cases). RCC subtypes each look different under the microscope and have a variable response to cancer therapy. African Americans (AAs) have higher incidence rates of RCC than European Americans (EAs) for unclear reasons. It is well documented that DNA changes called somatic copy number variations (SCNVs) are associated with increased cancer risk, differences in drug response, and a variety of health outcomes in kidney cancer patients. However, most of the studies that contributed to our understanding were performed in EA populations. Very few were carried out in diverse populations, including AAs. A recent kidney cancer study discovered AAs have DNA mutation profiles that differ from EAs, and this can correlate with poor clinical outcomes. The proposed project would help to better understand how SCNVs may impact kidney cancer disease burden in AAs and EAs. Hypothesis: Kidney cancers from AA and EA patients have different SCNV profiles that can change their disease progression or treatment. Addressing the Gap: There are very few published studies that address differences in AAs and EAs with kidney cancer, which is limiting scientific advances in the field of kidney cancer health disparities. This work contributes to the knowledge gap. Innovation: First, this project studies if new genes have SCNV alterations in addition to those already known. Second, the proposed study measures racial differences of genomic instability by using both a standard approach and cutting-edge method. Third, this project will incorporate genetic ancestry (a biological construct), in addition to self-reported race (a social construct), to determine if increased West African ancestry is associated with increased cancer rates (as seen in prostate cancer disparities contexts). Short-Term Impact: This study can catalyze new investigations into other population-specific differences in kidney tumor biology between AAs and EAs. AAs with an increased risk of developing kidney cancer, or those with early stage disease, can be tested for a clinically relevant SCNV. If present, healthcare providers can recommend more frequent regular imaging tests (e.g., CT, MRI) or ultrasound scans to look for kidney tumors in this population. When found early through surveillance with these tests, kidney cancers can often be cured. Further genomic classification of AA patients with advanced stage kidney cancer based on clinically relevant SCNV could be used to determine prognosis, guide treatment decisions, and better predict patient response as demonstrated in other published clinical studies. Long-Term Impact: The discovery of novel biological factors contributing to kidney cancer health disparities (e.g., SCNAs) can lead to new culturally competent health interventions aimed at improving education and awareness of biological, environmental, and social determinants of health and modifiable risk factors in AAs and other at-risk populations. The short-term and long-term impacts are directly in line with recent Precision Medicine initiatives, which is an emerging approach for disease prevention and treatment that takes into account an individual’s genetic variation, environment, and lifestyle.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910425
Entities
People
- Khadijah A. Mitchell
Organizations
- Lafayette College
- United States Army