Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk

Nishanth Ulhas Nair*, Kuoyuan Cheng*, Lamis Naddaf, Elad Sharon, Lipika R. Pal, Padma S. Rajagopal, Irene Unterman, Kenneth Aldape, Sridhar Hannenhalli, Chi Ping Day, Yuval Tabach*, Eytan Ruppin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Cancer is a predominant disease across animals. We applied a comparative genomics approach to systematically characterize genes whose conservation levels correlate positively (PC) or negatively (NC) with cancer resistance estimates across 193 vertebrates. Pathway analysis reveals that NC genes are enriched for metabolic functions and PC genes in cell cycle regulation, DNA repair, and immune response, pointing to their corresponding roles in mediating cancer risk. We find that PC genes are less tolerant to loss-of-function (LoF) mutations, are enriched in cancer driver genes, and are associated with germline mutations that increase human cancer risk. Their relevance to cancer risk is further supported via the analysis of mouse functional genomics and cancer mortality of zoo mammals' data. In sum, our study describes a cross-species genomic analysis pointing to candidate genes that may mediate human cancer risk.

Original languageAmerican English
Article numbereabj7176
JournalScience advances
Issue number31
StatePublished - 5 Aug 2022

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