The findings could help explain why some people exposed to known cancer risks, such as smoking, never develop cancer while others do.
In a study in mice, researchers found that genetic ancestry directly influences how cancer-causing mutations behave and how the resulting cancers grow and interact within the body.
Uncovering why and how cancer behaves in different people is crucial to support the use of personalised medicine, which aims to tailor treatment to a specific patient for better outcomes, experts say.
Genetic puzzle
In the UK, more than 403,000 people are diagnosed with cancer each year with around 170,000 people dying from the disease annually, so finding new ways to tackle the disease is vital.
DNA damage through normal ageing and environmental exposures like sunlight, tobacco smoke or processed meat can lead to cancer. However, the process is far from predictable.
Many smokers, for example, never develop lung cancer, while some people who have never smoked do. The reasons for this are not fully understood as studies of human cancers are limited by the complexity of real life such as differences in lifestyle, environment, and the role genetics plays.
Controlled experiment
To understand the role of genetics, researchers from the universities of Edinburgh, Cambridge, Heidelberg and Yale recreated cancer development under controlled conditions.
Using four genetically distinct groups of mice, representing levels of genetic variation similar to those seen in human populations, the team exposed each group to the same DNA-damaging chemical comparable to those found in some processed meats.
They then tracked how tumours developed in remarkable detail, analysing whole genomes, gene activity, and tumour structure.
Despite identical exposure, the cancers that emerged followed strikingly different paths depending on genetic background.
Different pathways
The study, which was funded by Cancer Research UK, found that most tumours shared a common feature: disruption of a key cancer-driving pathway known as MAPK. However, how this disruption occurred and what happened next, varied widely.
Researchers observed differences in which genes were mutated, how tumours grew, the number of additional cancer-driving mutations and whether entire genomes were duplicated – a major step in cancer progression.
Even more striking, the same cancer-causing mutation could have different effects depending on genetic background, influencing critical pathways such as the body’s key tumour suppressor system.
By better understanding how inherited DNA influences cancer evolution, future approaches could improve prediction of cancer risk, allow medics to tailor treatments more effectively to individuals and help address disparities in cancer outcomes across populations, researchers say.