Genomic Differences Might Explain Kidney Cancer Disparity in African Americans

Targeted therapies have offered striking improvements in survival rates among white patients who are diagnosed with clear cell renal cell carcinoma (ccRCC) in recent years, but survival rates for African Americans have not budged, according to a recent study published in JAMA Oncology.

Now, researchers at the University of North Carolina at Chapel Hill may have discovered a piece of that troubling puzzle: intrinsic genomic differences between African American and white patients, including differences in vascular endothelial growth factor (VEGF) pathway gene expression--the target of several US Food and Drug Administration (FDA)-approved anticancer agents.

“Our study suggests there are differences in the cancer biology of clear cell kidney cancer that develop in African American patients as opposed to those that develop in white patients,” said senior study author William Y. Kim, MD, associate professor in the UNC School of Medicine, Genetics and Urology, in a news release.

“These genomic differences would predict decreased responsiveness to VEGF-targeted therapy and are a biologically plausible contributing factor to the worse survival of African American patients with ccRCC, even in the targeted therapy era,” Dr. Kim and his coauthors reported.

Importantly, however, the genetic differences are not likely on their own to explain all of the reported survival disparity, he was quick to add.

“While the genetic differences we saw suggest that African American patients have underlying biology that may contribute to their worse prognosis, we feel that access to health care and treatments also negatively impact their outcomes from kidney cancer,” Dr. Kim said.

The research team examined racial differences in somatic mutations and RNA expression levels in an analysis of genomic data from 419 ccRCC tumors from non-Hispanic white patients and 19 non-Hispanic African American patients from The Cancer Genome Atlas (TCGA), and in a validation analysis of 125 white and 10 African American patients’ tumor data from the GSE25540 dataset.

African American patients had significantly lower rates of VHL mutations (17% vs 50%; P = .04) and “were enriched in the ccB molecular subtype (79% in African American vs 45% in white patients; P = .005),” they reported. The ccB subtype is associated with worse patient prognosis.

The team also identified downregulation of hypoxia-inducible factor (HIF) and VEGF-associated pathway genes among African American patients.

 “We don’t know enough at this time to suggest that African Americans with kidney cancer should be treated differently, but it does underscore the need to investigate these findings further,” Dr Kim concluded.