Scientists say they have found an important reason why some people who smoke tobacco face a higher lifetime cancer risk than others.
Smoking is associated with at least 15 forms of cancer, and people who smoke are around 15 to 30 times more likely to develop lung cancer than those who do not.
Although the dangers of smoking are already well established, new findings suggest a person’s inherited DNA can also strongly affect how likely cancer is to develop.
A study from researchers at the University of Cambridge, published in Nature on July 27, 2026, examined how “inherited genes interacting with acquired genetic mutations to shape how tumours evolve”. The research was co-led by Professor Duncan Odom, Dr Sarah Aitken, and Professor Martin Taylor in collaboration with scientists from the University of Edinburgh and institutions across Europe and the US.
To investigate this, scientists at the Cancer Research UK Cambridge Institute used mice in an experimental model designed to show how inherited genetic differences can influence not only whether cancer begins, but also how it progresses.
The team used four groups of mice that were all susceptible to liver cancer, with each group representing a different genetic profile similar to the variation seen across humans.
The animals were given a single dose of diethylnitrosamine, or DEN, a liver carcinogen present in tobacco and some processed foods that can damage DNA in liver cells and eventually trigger cancer.
Environmental influences were kept to a minimum, as the mice were raised under controlled conditions from 15 days old. Because every mouse received the same dose of the carcinogen at the same age under identical conditions, the researchers were able to isolate the specific impact of inherited genetics on cancer development.
Researchers then examined the genomes of nearly 600 tumours and found that, in many cases, the cancers “acquired a cancer-driving mutation that activated the same cancer-promoting signalling system”.
In simple terms, that signalling system helps regulate how cells grow and how they develop into specialised cell types, and it is known to be involved in several types of cancer.
Even so, the study found that the inherited genetics of each mouse had a major impact on whether cancer emerged in the first place.
Senior author on the study, Professor Duncan Odom, said:
“Cancer does not arise entirely by chance. Although tumours often reach the same biological endpoint, the path to that endpoint is determined by an individual’s genetic background.
“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.”
Dr Sarah Aitken, Assistant Professor at Yale School of Medicine and first author on the research, also 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.
“Similarly, 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.”
Researchers cautioned that while the findings are significant, the study was conducted in mice and further research in humans will be needed to determine whether the same mechanisms operate in people. The research was largely funded by Cancer Research UK, the Medical Research Council, European Research Council, and Wellcome.