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Head injuries may be a risk factor for developing brain cancer

Previous studies have suggested a possible link between head injury and increased brain tumor rates, but the evidence is inconclusive. The UCL team identified a possible mechanism to explain this link, implying genetic mutations that act in concert with brain tissue inflammation to change the behavior of cells, making them more likely to become cancerous. While this study was largely performed in mice, it suggests that it will be important to explore the relevance of these findings to human gliomas.

The study was led by Samantha Dickson Head of the Brain Cancer Unit and Professor Simona Parrinello (UCL Cancer Institute). "Our research shows that a brain injury can contribute to an increased risk of developing brain cancer later in life," she said.

Gliomas are brain tumors that usually arise from neural stem cells. More mature brain cells, such as astrocytes, are thought to be less likely to give rise to tumors. However, recent findings have shown that astrocytes can again exhibit stem cell behavior after injury.

Professor Parrinello and his team therefore set out using a preclinical mouse model to investigate whether this trait could make astrocytes a tumor following brain trauma.

Young adult mice with brain damage were injected with a substance that permanently labels astrocytes red and disables the function of a gene called p53, which is known to have a vital role in suppressing many different cancers. A control group was treated in the same way, but the p53 gene was left untouched. A second group of mice underwent p53 inactivation without injury.

Professor Parrinello said: "Normally astrocytes are very branched -- they get their name from stars -- but what we found was that without p53 and only after an injury, astrocytes retracted their branches and became more rounded, cell-like, but something had changed. So we aged the mice, Then we looked at the cells again and found that they had completely reverted to a root-like state with markers of early glioma cells that were able to divide."

This suggested to Professor Parrinello and his team that mutations in certain genes synergize with time-increasing brain inflammation in the natural aging process caused by acute injury, which then increases the likelihood that astrocytes will initiate a cancer. Indeed, the transition to stem cell-like behavior was accelerated when the mice were injected with a solution known to cause inflammation.

The team then looked for evidence to support their hypothesis in human populations. Working with Dr Alvina Lai at UCL's Institute of Health Informatics, they consulted the electronic medical records of more than 20,000 people diagnosed with head trauma, and compared brain cancer rates to a control group matched for age, sex, and socioeconomic status. They found that patients who had a head injury were about four times more likely to develop brain cancer later in life than those without a head injury. It is important to keep in mind that the overall risk of developing brain cancer is low, estimated at less than 1% in lifetime, so the risk remains modest even after an injury.

Professor Parrinello said: "We know that normal tissues carry many mutations that seem to just sit still and have no significant effect. Our findings show that if an injury occurs alongside these mutations, it creates a synergistic effect. "Mutations seem to be kept in check even after brain injury. However, as we age, our mouse study shows that inflammation increases throughout the brain, but more intensely at the site of previous injury. It reaches a certain threshold, after which the mutation starts to manifest."


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