Cancer relevance of human genes

Background It is unclear how many of genes contribute to the biology of cancer. We hypothesize that genes that interact with core cancer gene (CCG) in a protein-protein interaction network (PPI) may have functional importance. Methods We categorized genes into 1- (n=6791), 2- (n=7724), 3- (n=1587), and >3-steps (n=362) removed from the nearest CCG in the STRING PPI and demonstrate that the cancer-biology related functional contribution of the genes in these different neighborhood categories decreases as their distance from the CCGs increases. Results Genes closer to cancer genes manifest greater connectedness in the network, show greater importance in maintaining cell viability in a broad range of cancer cells in vitro, are also under greater negative germline selection pressure in the healthy populations, and have higher somatic mutation frequency and cancer effect. Conclusions Approximately 70% of human genes are 1 or 2 steps removed from cancer genes in protein network and show functional importance in cancer-biology. These results suggest that the universe of cancer-relevant genes extends to thousands of genes that can contribute functional effects when dysregulated.