Genetic Background Determines Cancer Risk in Mouse Study

Researchers sequenced nearly 600 liver tumours from four inbred mouse strains that were all given the same dose of the carcinogen diethylnitrosamine. By eliminating environmental variation, the study, published in Nature and led by the University of Cambridge and the University of Edinburgh with contributions from US laboratories, showed that the inherited genetic makeup of each strain dictated which driver genes – such as Braf, Hras, Egfr or Kras – were mutated, how quickly tumours appeared and whether whole‑genome duplication occurred.

Strains with highly susceptible germline backgrounds required only a single driver event and often displayed whole‑genome doubling associated with Braf mutations, while resistant strains needed multiple hits and showed greater early sub‑clonal loss. The findings highlight a strong germline‑somatic epistatic interaction that shapes cancer evolution, suggesting that host genetics can profoundly influence cancer risk even under identical environmental exposures.