Abstract C059: Clinical and molecular profile of renal cell carcinoma in Hispanic Americans, Native Americans, and European Americans

Abstract

Abstract Background: Racial/ethnic minority groups, including Hispanic Americans (HAs) and Native Americans (NAs), have a heavier burden of kidney cancer with a higher incidence and mortality than European Americans (EAs). However, HAs and NAs are under-represented in clinical and molecular genomic studies of renal cell carcinoma (RCC), the most common type of kidney cancer, and clinical and molecular characteristics of RCC among them are also unknown. We investigated variations in clinical and molecular characteristics of RCC patients. Methods: A total of 284 patients, including 90 HAs (31.6%) and 22 NAs (7.7%), who were diagnosed with RCC and without prior diagnosis of cancer were included to understand the patients' clinical characteristics. A subset of 51 samples were selected to screen for somatic mutations on the VHL gene, and 33 samples were selected for whole-transcriptome sequencing analysis. Results: Compared to EAs, HA and NA patients were diagnosed with RCC at younger ages (P<0.001). HA had about 5 years younger average age at diagnosis than EAs (55.2 vs. 60.6) and an over 2-fold increased odds of diagnosis before age 60 years (OR 2.50, 95% C.I.: 1.36-4.60). Mean age of diagnosis among NAs was 48.9, and NAs had more than 4-fold higher odds of diagnosis at a younger age (OR 4.12, 95% C.I.: 1.31-12.95). NA patients had higher body mass index than EA patients with 77.3% of NA obese patients. Diabetes was more common in HA (45.6%) and NA (50.0%) patients compared to EA (19.6%) patients. An RCC histologic subtype, clear cell RCC (ccRCC), was more common in HAs and NAs than EAs. Over 90% of HA patients had ccRCC, while only 77.6% of EA patients had ccRCC. HAs had increased odds of diagnosis with ccRCC compared to EAs (OR 2.39, 95% C.I.: 1.01-5.67). Among HAs, older patients were more likely to have advanced-stage RCC diagnosis (OR 7.06, 95% C.I.: 1.46-34.11). HAs who used Spanish as their primary language were more likely to have radical nephrectomy rather than partial nephrectomy (OR 5.13, 95% C.I.: 1.23-21.33). We detected pathogenic somatic mutations on the VHL gene, which is known to cause von Hippel-Lindau syndrome, in 4 patients, and these patients were younger than the patients without these mutations (45.5 vs. 57.1). We were able to assign 32 out of 33 patients into molecular subtypes (ccA and ccB). Molecular subtype could not be assigned to one HA patient with high-grade and advanced-stage ccRCC. Molecular subtype, ccA, was more common in HAs than EAs (64.3% vs. 41.2%), but this difference was not statistically significant. One gene, HABP2, showed evidence of differential expression between HA and EA tumors (PADJ<0.05) and was downregulated in HA tumors with log2 fold change <-2.0. Conclusion: HA and NA RCC patients had different clinical and molecular characteristics from EA patients. Impact: As we move toward a precision medicine approach for RCC care, it is necessary to better understand the clinical and molecular characteristics of these underserved HA and NA populations with high kidney cancer burden. Citation Format: Ken Batai, Alfredo Harb de la Rosa, Francine Gachupin, Elliot Imlaer, Erika R. Bracamonte, Bruce Seligmann, Benjamin R. Lee. Clinical and molecular profile of renal cell carcinoma in Hispanic Americans, Native Americans, and European Americans [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C059.