Genetic factors associated with cancer racial disparity - an integrative study across twenty-one cancer types

It is well known that different racial groups have significantly different incidence and mortality rates for certain cancers. It has been suggested that biological factors play a major role in these cancer racial disparities. Previous studies on the biological factors contributing to cancer racial disparity have generated a very large number of candidate factors, although there is modest agreement among the results of the different studies. Here, we performed an integrative analysis using genomic data of 21 cancer types from TCGA, GTEx, and the 1000 Genomes Project to identify biological factors contributing to racial disparity in cancer. We also built a companion website with additional results for cancer researchers to freely mine. Our study identified genes, gene families, and pathways displaying similar differential expression patterns between different racial groups across multiple cancer types. Among them, XKR9 gene expression was found to be significantly associated with overall survival for all cancers combined as well as for several individual cancers. Our results point to the interesting hypothesis that XKR9 could be a novel drug target for cancer immunotherapy. Bayesian network modeling showed that XKR9 is linked to important cancer-related genes, including FOXM1, cyclin B1, and RB1CC1 (RB1 regulator). In addition, metabolic pathways, neural signaling pathways, and several cancer-related gene families were found to be significantly associated with cancer racial disparities for multiple cancer types. Single nucleotide polymorphisms (SNPs) discovered through integrating data from the TCGA, GTEx, and 1000 Genomes databases provide biologists the opportunity to test highly promising, targeted hypotheses to gain a deeper understanding of the genetic drivers of cancer racial disparity and cancer biology in general.