Scientists have found what they say is the first direct evidence of the powerful role our genetic makeup plays in influencing our risk of cancer.

The study by teams across the world has found a strong link between inherited genes interacting with acquired genetic mutations to shape how tumours evolve.

The findings could explain why some people are more susceptible to cancer than others in the same environment and suggest that future cancer prevention and screening strategies may need to account more carefully for inherited genetics and population diversity.

The research, carried out in mice, suggests that responses to DNA-damaging cancer treatments could differ depending on a patient’s background genetics, strengthening the case for a more personalised approach to treatment.

The study is the result of years of international collaboration, between the University of Cambridge, University of Edinburgh, and others around Europe and the US, and was co-led by Professor Duncan Odom, Dr Sarah Aitken and Professor Martin Taylor.

The team explained tumours arise when our DNA accumulates errors, or mutations, causing the cells to grow faster and ignore signals that would otherwise instruct damaged cells to die before they can cause harm. Environmental exposures – for example, cigarette smoke or sunlight – influence how much DNA damage occurs, and inherited genetic alterations can alter how many mutations accumulate.

Not everyone exposed to the same environmental risk factors will develop cancer, however. Most smokers do not develop lung cancer – and some non-smokers develop lung cancer. The reason why is almost certainly related to our inherited genetic makeup, but finding direct evidence has proved challenging in patient cohort studies. Even though many studies have suggested that inherited genetic differences affect cancer risk, proving this link has been difficult because individuals within – and between – human populations vary in lifestyle, environment, and exposure history.

In experiments largely carried out at the Cancer Research UK (CRUK) Cambridge Institute at the University of Cambridge, scientists developed an experimental approach that allowed them to control environmental factors experimentally and show that genetic background itself can alter how tumours arise and evolve.

Senior author Professor Duncan Odom, who led the research while at the CRUK Cambridge Institute and is now based at DKFZ (German Cancer Research Centre) in Heidelberg, Germany, 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.”

The researchers said the findings have implications for cancer screening and precision medicine.

First author Dr Sarah Aitken, assistant professor at Yale School of Medicine, 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.

“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.”

Cancer Research UK research information lead Dr Sam Godfrey said: “This study gives us a fascinating hint that our inherited genes might have a big influence on the way that cancers develop after DNA damage.

“We still need to see more research before we can understand what this means in humans, but this finding could change our understanding of how cancer starts, and lead to more powerful and precise ways of tackling cancer.”