Genetics 'shape' how cancer develops, say Scots scientists
Research helps bring scientists step closer to ‘truly personalised’ cancer care
Genetic differences play a vital role in determining how cancerous tumours develop and evolve, helping to explain why some people get the disease while others do not, according to a new study involving Scots scientists.
The international team of researchers found that genetic ancestry can directly influence how cancer-causing mutations behave, and how the resulting cancers grow and interact within the body after DNA damage occurs.
The team, which included scientists from the University of Edinburgh, said genetic factors can influence differences in which genes become mutated, how tumours grow, the number of additional cancer-driving mutations, and whether entire genomes were duplicated - a major step in cancer progression.
Those behind the study said the findings have important implications for cancer screening, diagnosis, and prognostication as well as profound implications for precision medicine.
The research, published in the leading journal, Nature, 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 tracked how tumours developed in 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 - the 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 mutations and tumour growths. Even more striking, the study found that 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.
The study’s co-lead, Professor Martin Taylor, from the Institute of Genetics and Cancer at the University of Edinburgh, said: “Cancer doesn’t develop in a vacuum. Our research has shown that inherited genetics can fundamentally shape how tumours grow and evolve.
“Understanding this interaction between an individual’s inherited genetics and new cancer-driving mutations caused by DNA damage brings us a step closer to truly personalised cancer care.”
The research, funded by Cancer Research UK, could help explain why some people exposed to major cancer risks, such as smoking, never develop the disease, although other factors, such as differences in lifestyle, environment, also play a part.
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.
The study is the result of years of international collaboration between the universities of Edinburgh, Yale and Cambridge and forms part of the Liver Cancer Evolution consortium, led by Prof Taylor, Professor Duncan Odom from the German Cancer Research Centre, and Yale University’s Dr Sarah Aitken.
Cancer Research UK’s 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.”
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