Genetic Differences Explain Survival Disparity in African Americans With Kidney Cancer
Several genetic differences uncovered in an analysis of data from The Cancer Genome Atlas (TCGA) are biologically plausible contributing factors for the worse survival of African American patients with clear cell renal carcinoma, even in the era of targeted therapy.1
Clear cell renal carcinoma is the most common type of kidney cancer. These findings could help explain why African American patients with this disease have lower survival rates than white patients. This difference in survival rates is independent of age, sex, tumor stage, and other variables.
“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 William Y. Kim, MD, a University of North Carolina (UNC) Lineberger member and associate professor in the UNC School of Medicine Department of Medicine, Genetics, and Urology in Chapel Hill, and senior author of the study.
“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 treatment also negatively impacts their outcomes from kidney cancer,” Kim said. “Additional research is needed to confirm this finding.”
This new study involved analysis of genomic data from TCGA, including 419 clear cell renal cell carcinoma tumors from non-Hispanic white patients and 19 from non-Hispanic African American patients. The findings were validated against a set of 125 white and 10 African American patient tumors from another publicly available data set.
A key finding was that African Americans were less likely to have inactivated von Hippel-Lindau (VHL) gene. Mutations that inactivate VHL can increase VEGF expression, which promotes blood vessel growth and is targeted by multiple drugs for kidney cancer. Only 17% of the African American patients had VHL mutations (2 of 17 patients), which is few compared with 50% of white patients (175 of 351 patients). Furthermore, the tumors of the African American patients had down-regulated VEGF signaling relative to those of the white patients.
Another finding was an increased frequency of the molecular tumor subtype known as ccB in African American patients. The ccB subtype is associated with lower survival. It occurred in 79% (15 of 19 patients) of the African American patients, compared with 45% of the white patients.
“There are clear genetic differences in clear cell kidney tumors that develop in African Americans compared to whites,” Kim said. “While we believe that these differences could impact outcomes we don't know enough at this time to suggest that African American's with kidney cancer should be treated differently, but it does underscore the need to investigate these findings further.”
The study was supported by the American Association for Cancer Research, Kure It Program, and the Department of Defense.
1. Krishnan B, Rose TL, Kardos J, et al. Intrinsic genomic differences between African American and white patients with clear cell renal carcinoma [published online ahead of print March 24, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.0005.