Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk.
Sci Adv
; 8(31): eabj7176, 2022 08 05.
Article
in En
| MEDLINE
| ID: mdl-35921407
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genomics
/
Neoplasms
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Adv
Year:
2022
Document type:
Article
Affiliation country:
United States