A long-standing puzzle in cancer biology—why some lifelong smokers develop lung cancer while others do not, or why not everyone exposed to sunlight gets skin cancer—may have moved closer to a solution. A study published in Nature provides the first experimental evidence that inherited genetic makeup plays a decisive role in how cancers evolve after DNA damage.
Researchers at the Cancer Research UK Cambridge Institute and the German Cancer Research Centre (DKFZ) in Heidelberg used four genetically distinct strains of mice, chosen to reflect the level of genetic diversity found in human populations. They exposed all animals to identical doses of diethylnitrosamine, a liver carcinogen present in tobacco smoke and some processed foods, at the same age—15 days—under controlled conditions.
Despite receiving the same carcinogenic insult, the mice developed cancers through markedly different evolutionary routes depending on their genetic background. The team analysed nearly 600 tumours to reconstruct how the cancers evolved. Although many tumours ultimately activated the same biological pathways that promote cancer growth, they reached that destination via different mutations and genetic changes.
Implications for screening and treatment
“We’ve been able to show for the first time the extent to which genetic background influences both the mutation processes and the pathways leading to tumour development,” said Duncan Odom, who led the research while at the CRUK Cambridge Institute and is now based at DKFZ in Heidelberg. The findings suggest that inherited DNA not only affects cancer risk but also shapes the tumour’s evolutionary trajectory once it begins to form.
Sarah Aitken, Assistant Professor at Yale School of Medicine and a co-author of the study who also worked on the research at the CRUK Cambridge Institute, said: “If genetic background influences both cancer risk and the evolutionary trajectory of tumours, future cancer prevention and screening strategies will need to take into account inherited genetics and population diversity.”
The researchers also propose that inherited genetics could influence how patients respond to treatments that target tumour DNA, including certain forms of chemotherapy and radiotherapy. “How people respond to cancer drugs is likely to differ depending on their inherited genetics, and so we may need to tailor our diagnostics and treatments accordingly,” Aitken added.
Sam Godfrey, Cancer Research UK’s research information lead, described the work as “a fascinating hint that our inherited genes might have a big influence on the way that cancers develop after DNA damage.” He cautioned that more research is needed to confirm the findings in humans, but added that “this finding could change our understanding of how cancer starts, and lead to more powerful and precise ways of tackling cancer.”
The study underscores the growing push toward personalised medicine in oncology, a field where European institutions have been active. For instance, AstraZeneca's recent financial results highlighted the company's focus on cancer drug sales, reflecting the continent's investment in targeted therapies. Meanwhile, broader health trends such as longer lives not necessarily being healthier years reinforce the need for more nuanced prevention strategies.
If the genetic influence on tumour evolution is confirmed in human studies, it could open the door to more tailored approaches to risk assessment and treatment selection, moving beyond the one-size-fits-all model that has dominated cancer care for decades.
