Scientists have new proof that our genes play a big part in cancer risk. A new study shows that the genes we inherit work together with new mutations to shape how tumours grow. This is the first direct evidence of this process in action.
The discovery may explain a puzzle doctors have long faced. Some people face the same risks, like smoking, yet only some of them get cancer. Inherited genes appear to be a key reason for this discrepancy.
The study appears today in the journal Nature. Researchers from Cambridge, Edinburgh, and other US and European centres collaborated on it. The team of Professor Duncan Odom, Dr Sarah Aitken, and Professor Martin Taylor led the team. The team of Professor Duncan Odom, Dr Sarah Aitken, and Professor Martin Taylor led the team. The team was led by Professor Duncan Odom, Dr Sarah Aitken, and Professor Martin Taylor.
How Cancer Starts
Cancer begins when DNA picks up damage over time. This damage is called mutation. As mutations build up, cells start growing out of control. They also stop responding to signals that would normally make damaged cells die off.
Things in our environment, such as cigarette smoke or strong sunlight, can cause this kind of damage. But genes we inherit from our parents can also affect how much damage builds up and how the body handles it.
This phenomenon is why most smokers never get lung cancer, while some non-smokers do. Scientists have long suspected genetics was behind this pattern. But it has been challenging to prove. People’s lives differ too much. Diet, environment, and habits all vary, making it tough to isolate the effect of genes alone.
A Careful Experiment
To solve this problem, the research team turned to mice. They bred four different mouse strains. Each strain carried a different level of natural risk for liver cancer. Together, the strains reflected a range of genetic diversity similar to what is seen in humans.
Every mouse was then given the same single dose of a chemical called diethylnitrosamine, or DEN. This substance is found in tobacco smoke and some processed foods. It is known to damage liver cells and trigger tumour growth. All mice received the dose at exactly 15 days old, under the same lab conditions. This removed environmental differences from the equation entirely.
The team then studied the mice closely. They sequenced the genetic code of nearly 600 tumours. They also studied gene activity and compared untreated mice across the different strains. This let them trace how each tumour began and developed over time.
What They Found
In nearly every mouse, tumours activated the same key growth pathway, called MAPK. This pathway controls how cells grow and change, and it plays a major role in many cancers.
But the specific mutation that switched on this pathway was different depending on the mouse’s genetic background. These differences also affected other cancer-related pathways. Interestingly, some strains showed a strong tendency toward whole-genome duplication. This is when a cell’s entire set of chromosomes gets copied twice.
Professor Odom, now at the German Cancer Research Centre in Heidelberg, said cancer is not simply random. He explained that while tumours often end up at a similar point, the route they take depends heavily on a person’s genetic makeup.
What This Means for Treatment
The researchers believe this work could reshape cancer prevention and screening in the future. Dr Aitken, now at Yale School of Medicine, said screening approaches may need to consider both inherited genes and diversity across populations. She added that people may also respond differently to cancer drugs based on their genetic background, meaning treatments could eventually be tailored to the individual.
Dr Sam Godfrey of Cancer Research UK called the findings an important early clue. He noted that more research is needed to confirm how this applies to humans. Still, he said the work could reshape how scientists understand the beginnings of cancer, paving the way for more precise treatments in the future. The study Cancer Research UK, the Medical Research Council, the European Research Council, and Wellcome funded the study. by Cancer Research UK, the Medical Research Council, the European Research Council, and Wellcome.
