Abdominal Adiposity in Early-Onset and Aggressive Clear Cell Renal Cell Carcinoma and Health Disparities
Abstract
Kidney cancer is one of the top ten most common cancers in the United States. Individuals who are obese, particularly during adolescence and early adulthood, have an increased risk for kidney cancer. Kidney cancer incidence has increased significantly over the past 40 years, and its incidence increased more rapidly among adults aged 50 years or younger. A similar trend is seen in obesity rates during the same decades. Hispanic Americans (HAs) and Native Americans (NAs) have a higher prevalence of obesity and a heavier kidney cancer burden with higher incidence and mortality rates than European Americans (EAs). Similarly, kidney cancer incidence and obesity rates increased among U.S. Service Members and Veterans, and obesity rates among them are higher than the U.S. civilian populations. Among renal cell carcinoma (RCC) patients at Banner University Medical Center Tucson (BUMCT), obesity was common among HAs and NAs, and HA and NA patients as well as obese patients were diagnosed with RCC at a younger age (under the age of 50). However, HAs and NAs are under- and poorly represented in kidney cancer research. The molecular genomic and metabolomic characteristics of clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, among them, are unknown, and it is not fully understood how obesity, particularly abdominal adiposity, affects age of onset, ccRCC aggressiveness, and genomic and metabolomic characteristics. Our long-term goal is to develop diagnostic and prognostic biomarkers that can be used in racially/ethnically diverse patient populations. This is a Basic Science research project using genomic and metabolomic approaches (FY20 KCRP Area of Emphasis) to characterize early-onset (diagnosis before the age of 50 years) and aggressive ccRCC. This project will investigate if abdominal adiposity is associated with early-onset ccRCC genomic and metabolomic profiles and if abdominal adiposity and identified genes and metabolites are associated with aggressiveness. We hypothesize that abdominal adiposity significantly influences age of onset, and gene expression and metabolomic characteristics of early-onset and aggressiveness. This proposed study will pursue two specific aims: (1) determine relationships between abdominal adiposity, age of onset, and aggressiveness and (2) identify gene expression signatures in tumors and metabolomic signatures in the blood that are associated with abdominal adiposity, age of onset, and aggressiveness. Our study is innovative in three ways. First, our project will address the gap in kidney cancer precision medicine research by a higher representation of racial/ethnic minority groups. BUMCT is uniquely located and has high representations of HA and NA RCC patients. By focusing on previously underrepresented racial/ethnic groups with a high burden of kidney cancer and obesity-related comorbid conditions, we will gain a better understanding of the biological basis of early-onset and aggressive ccRCC. Second, instead of using imprecise measurements of obesity based on body mass index, pre-operative CT and MRI scans will be used to measure abdominal adiposity, which is shown to be a better predictor of oncologic outcomes. Third, we will use a cost-effective and efficient transcriptomic and metabolomic profiling method. This will allow us to use a multi-omics approach, which was previously possible only for large-scale projects. We will use a novel computational biology approach that combines two different types of data, gene expression and serum metabolites, for the same patients to detect commonly altered pathways and driver genes. The inclusion of previously understudied minority groups, along with more precise measurements of adiposity and a novel multi-omics approach, will allow us to discover novel genomic and metabolomic signatures and associations, which otherwise are missed in studies using a single approach or in studies among predominantly EA p
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110811
Entities
People
- Ken Batai
Organizations
- United States Army
- University of Arizona