Study links inherited genetics to cancer susceptibility and progression

An international team of scientists, including researchers at the Institute of Genetics and Cancer, has discovered that inherited genetic differences play a crucial role in shaping how cancers develop and evolve after DNA damage to the body occurs. 

The findings could help explain why some people exposed to major cancer risks, such as smoking, never develop disease while others do.

The research, carried out in mice by researchers at Edinburgh, Cambridge, Heidelberg and Yale universities, shows that genetic ancestry can directly influence how cancer-causing mutations behave and how the resulting cancers grow and interact within the body.

Personalised medicine is a growing area of cancer research which aims to tailor treatment to a specific patient but more information is needed to understand why and how cancer behaves in different people.

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.

To understand the role genetics plays, the research team recreated cancer development under controlled conditions.

Using four genetically distinct groups of mice, representing levels of genetic variation similar to those 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.

The study 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.