A controlled study in mice has shown that inherited genetics strongly influence how tumors develop following DNA damage. The findings, published in Nature, suggest that genetic background shapes cancer risk and tumor evolution.
Researchers bred four strains of mice with varying susceptibility to liver cancer and exposed each to the same dose of the carcinogen diethylnitrosamine at 15 days old. They then sequenced nearly 600 tumors to track how the cancers evolved under identical environmental conditions.
All tumors activated the MAPK signaling pathway, yet the specific driver mutations differed based on each strain's genetic background. Some strains also showed higher rates of whole-genome duplication.
Professor Duncan Odom said the results demonstrate that an individual's genetic background determines the path to tumor development. Dr. Sarah Aitken noted that future screening and treatment strategies may need to account for inherited genetics and population diversity.
The work was conducted at the Cancer Research UK Cambridge Institute and involved collaborators from the University of Edinburgh and other European and US institutions.
