This article is more than 5 years old. Information may no longer be current.
Tumor biology may explain racial disparities in clear cell RCC survival
Click Here to Manage Email Alerts
Distinct differences in tumor biology may explain racial disparities in survival of patients with clear cell renal cell carcinoma, according to study results.
Studies conducted prior to the development of targeted therapy demonstrated that black patients with renal cell carcinoma have shorter OS than white patients. OS among white patients has improved considerably since the advent of targeted therapy, whereas survival in black patients has remained unchanged, according to study background.
No studies have examined the potential genetic variances in clear cell renal cell carcinoma (ccRCC) that might contribute to this disparity.
Bhavani Krishnan, PhD, postdoctoral fellow at Lineberger Comprehensive Center at University of North Carolina at Chapel Hill, and colleagues used The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset to identify 438 patients (white, n = 419; black, n = 19) with ccRCC.
The researchers analyzed incidence of the most common gene mutations — VHL, PBRM1, SETD2, KDM5C, PTEN, BAP1, MTOR, TP53 and PI3KCA — to determine if differences existed in the somatic mutation rate and gene expression of tumors in black patients compared with white patients.
The GSE25540 dataset (white, n = 125; black, n = 10) served as validation.
Researchers determined 175 of 351 evaluable white patients (50%) and two of 12 evaluable black patients (17%) presented with VHL mutations (P = .04). No racial differences existed in the mutational frequencies of other gene mutations.
Researchers confirmed these results in the validation set.
Krishnan and colleagues then assessed RNA expression of VEGF ligands and receptors to assess downstream effects of VHL loss.
Black patients appeared significantly less likely to express the VEGFA ligand, as well as the FLT-1 (VEGFR-1) and KDR (VEGFR-2) receptors. Researchers also determined genes associated with hypoxia-inducible factor (HIF) activation appeared upregulated in white patients, and that several VEGF and HIF signatures were negatively enriched in black patients.
“We therefore postulate that a significantly larger proportion of tumors from African American patients may have a HIF–independent and VEGF–independent propensity for aggressiveness, resulting in resistance to the commonly used VEGF–targeted therapies,” Krishnan and colleagues wrote.
Black patients also showed a predominance for the ccB subtype (79% vs. 45%; P = .005), which is associated with shorter survival.
Krishnan and colleagues acknowledged that disparities in health care delivery also may contribute to survival differences between races.
“Comprehensive population-based studies will be needed to define correlations between race and etiologic heterogeneity,” they wrote. – by Kristie L. Kahl
Reference:
Krishnan B, et al. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.0005.
Disclosure: The researchers report no relevant financial disclosures.