Genomic Differences in African-Americans with ccRCC May Contribute to Responsiveness

Genomic differences in African-American patients with clear cell renal cell carcinoma (ccRCC) compared to white patients may contribute to decreased responsiveness to vascular endothelial growth factor (VEGF)-targeted therapy and worse survival, according to a study published in JAMA Oncology.

Researchers led by Bhavani Krishnan, PhD, of the University of North Carolina at Chapel Hill looked at 438 patients with ccRCC who were identified through The Cancer Genome Atlas (TCGA) clear cell kidney (KIRC) dataset.

Findings were validated through the GSE25540 dataset which contained 135 patients. They collected tumor samples from numerous cancer centers and examined for racial differences in somatic mutation rates and RNA expression.

From 419 patients who were identified as non-Hispanic white and 19 who were non-Hispanic African-American, as well as 10 African-American ccRCC patients and 125 white patients identified through the GSE25540 dataset, African-American patients were found to be significantly less likely to have VHL mutations. They were also enriched in the ccB molecular subtype, which carries a worse prognosis.

Additionally, the study found that RNA expression analysis revealed relative down-regulation of hypoxia-inducible factor (HIF) and VEGF-associated pathways in African-American patients compared to white patients.

Reference

1. Krishnan B, Rose TL, Kardos J, et al. Intrinsic genomic differences between African American and white patients with clear cell renal cell carcinoma. [published online ahead of print March 24, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.0005.