Abstract 3665: Clear cell renal cell carcinoma molecular characteristics in Hispanic Americans compared to European Americans
Authors: Batai Ken , Chen Yuliang , Rheinheimer Brenna , Heimark Ron , Ellis Nathan , Lee Benjamin R. 
Published: June 2022

Abstract
Background: Hispanic Americans (HAs) have higher incidence and mortality rates of renal cell carcinoma (RCC) than European Americans (EAs). Despite the disparate burden of RCC, tumor molecular characteristics among HAs are unknown. This study explored clear cell RCC (ccRCC) molecular difference between HAs and EAs.
Methods: Paraffin embedded surgical specimens of ccRCC patients who underwent nephrectomy for a treatment of RCC were obtained. Three exons of VHL gene were screened for somatic mutations in a total of 150 patients. 96 patients were included for TempO-Seq analysis. A centroid-based approach with 34 gene set was used to assign molecular subtype (ccA or ccB). DESeq2 was used for differential gene expressional analysis.
Results: HAs were younger (mean age of 55.7 vs. 61.2) and had slightly higher mean Body Mass Index (BMI, 32.1 vs. 30.3). More HAs reported that they never smoked (71%) compared to EAs (46%). 73 somatic mutations in coding regions of VHL were found in 56 patients (37.3%), and 11 patients had more than 2 somatic mutations in coding regions. Mutations in coding regions were more common in EAs (41.5%) than HAs (35.5%), but the difference was not statistically significant (p=0.49). When we focused on moderate or high impact mutations, EAs had mutations at higher frequency than HAs (40.2 vs. 27.4%; p=0.07 after adjusting for age and sex). Frequency of somatic mutations was also higher for former (30.3%) and current smokers (40.0%) compared to non-smokers (24.3%). After including smoking history in the regression model, HA ethnicity was not associated with presence of high/moderate impact somatic mutations. HAs had a higher frequency of ccA subtype than EAs (61.9% vs 45.8%). ccA subtype was also more common in patients with BMI&gt;35 (65.2%) than patients with BMI&lt;25 (45.0%). In the adjusted model, HAs had significantly increased odds of having ccA (OR 3.34, 95%CI: 1.17-9.52). Haptoglobin (HP) gene was most significantly over-expressed in high-grade compared to low-grade ccRCC in an analysis including all samples (log2 fold change 4.0, adjusted-p=1.7x10-12). HP was highly over-expressed in high-grade compared to low-grade ccRCC in EAs (log2 fold change 5.2, adjusted-p=4.9x10-9), but not in HA tumors (log2 fold change 2.5, adjusted-p=0.06).
Conclusion: HA and EA tumors have different molecular characteristics potentially due to differences in prevalence of behavioral risk factors.
Impact: Different molecular characteristics in racial/ethnic groups may impact clinical treatment in diverse patient populations.
Citation Format: Ken Batai, Yuliang Chen, Brenna Rheinheimer, Ron Heimark, Nathan Ellis, Benjamin R. Lee. Clear cell renal cell carcinoma molecular characteristics in Hispanic Americans compared to European Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3665.