Suffering head injuries may increase risk of developing brain tumors

By James Gamble via SWNS

Suffering a head injury could increase the risk of developing a brain tumor four times, a new study shows.

A team of scientists at University College London (UCL) found a link between inflammation in the brain and dangerous mutations in brain cells which make them more likely to become cancerous.

The researchers from the UCL Cancer Institute first analyzed changes in the brain cells of mice with head injuries before studying data in humans to support their hypothesis.

The study concluded that injuries to the head may contribute to an increased risk of developing brain cancer in later life.

The UCL team focused on a "rare but aggressive" form of tumor called a "glioma."

Gliomas are tumors, which occur in neural stem cells in the brain - the stem cells of the nervous system.

More mature cells such as star-shaped astrocyte cells - the most abundant cell type in the brain - have previously been considered less likely to give rise to tumors.

However, more recent studies have shown that, following injury, astrocytes can revert to exhibiting the behavior of stem cells.

The researchers decided to test this hypothesis by injecting young adult mice with a substance which permanently labels astrocytes in red, and disabled a gene - called p53 - believed to be crucial in suppressing many different cancers.

A control group of mice were treated the same way, but with their p53 left intact.

A third group had their p53 gene deactivated but had suffered no head trauma.

The scientists, led by Professor Simona Parrinello, found that the astrocyte cells in the mice with previous head trauma "reverted" into stem cells, showing signs of 'early glioma cells' which could divide.

Prof. Parrinello, Head of the Samantha Dickson Brain Cancer Unit and co-lead of the Cancer Research UK Brain Tumor Center of Excellence, explained: "Our research suggests that a brain trauma may contribute to an increased risk of developing brain cancer in later life."

"Normally astrocytes are highly branched – they take their name from stars – but what we found was that without p53, and only after an injury, the astrocytes had retracted their branches and become more rounded.

"They weren’t quite stem cell-like, but something had changed.

"So we let the mice age, then looked at the cells again and saw that they had completely reverted to a stem-like state with markers of early glioma cells that could divide.”

This suggested to the team that mutations in certain genes "synergized" with brain inflammation caused by injury and increased over time to make astrocytes more likely to initiate cancer.

Furthermore, when the mice were injected with a solution known to cause inflammation, this process of change to stem cell-like behavior accelerated.

The study, published in the journal Current Biology, then turned to evidence pointing towards a similar hypothesis in humans.

The researchers studied the medical records of more than 20,000 people who had been diagnosed with head injuries; comparing the rate of brain cancer with a control group of people who matched them in age, sex and socioeconomic status.

This analysis showed that those patients who experienced a head injury were nearly four times more likely to develop brain cancer in later life than those who have not suffered such trauma.

However, the study team emphasized the fact that the risk of developing brain cancer is low overall - estimated at less than one percent over a lifetime - so the risk, even after an injury, is still modest.

Prof. Parrinello added: "We know that normal tissues carry many mutations which seem to just sit there and not have any major effects.

"Our findings suggest that if on top of those mutations, an injury occurs, it creates a synergistic effect.

"In a young brain, basal inflammation is low so the mutations seem to be kept in check even after a serious brain injury.

"However, upon aging, our mouse work suggests that inflammation increases throughout the brain but more intensely at the site of the earlier injury.

"This may reach a certain threshold after which the mutation now begins to manifest itself.”

The collaborative study involved researchers from the UCL Cancer Institute, UCL Laboratory for Molecular Cell Biology and UCL Institute of Health Informatics alongside external collaborators from Imperial College London; with funding provided by Cancer Research UK, the Oli Hildson foundation through the Brain Tumor Charity and the Medical Research Council.