Scientists may be one step closer to new cancer treatments after discovering thousands of genetic mutations that increase risk of the disease.
Experts have long known that many cases are linked to problems with a gene called BAP1, also known as ‘the tumour protection gene’, that cause it to malfunction and fuel cancer growth.
But until now, they were unsure which specific changes to look out for.
Now British researchers have an answer after discovering more than 5,000 harmful faults which can disrupt its protective effects.
They also found around a fifth of these possible changes were caused by pathogens such as viruses, significantly increasing the risk of developing cancers of the eye, lung lining, brain, skin, and even kidney.
Until now, experts were unsure exactly which specific genetic changes to look out for in the ‘tumour protection’ gene BAP1 that cause it to malfunction and fuel cancer growth. But researchers in the UK have now discovered more than 5,000 harmful changes to the protein’s DNA which can disrupt its protective effects. Pictured, researchers at the Wellcome Sanger Institute in Cambridgeshire
They found around a fifth of these possible changes were caused by pathogens, significantly increasing the risk of developing cancers of the eye, lung lining, brain, skin, and even kidney
In what could be good news for thousands of Brits at risk of the disease, scientists said the discovery could help patients get targeted treatments quicker and open the door for developing new drugs.
Professor Clare Turnbull, an expert in cancer genetics at The Institute of Cancer Research in London, and consultant in clinical cancer genetics at The Royal Marsden NHS Foundation, said: ‘This research could mean more accurate interpretation of genetic tests, earlier diagnoses and improved outcomes for patients and their families.’
Dr Andrew Waters, an expert in cancer gene mutations at the Wellcome Sanger Institute, added: ‘Previous approaches for studying how variants effect function in genes have been on a very small scale, or exclude important contexts that may contribute to how they behave.
‘Our approach provides a true picture of gene behaviour, enabling larger and more complex studies of genetic variation.
‘This opens up new possibilities for understanding how these changes drive disease.’
Under the research, scientists at the Wellcome Sanger Institute, the Institute of Cancer Research, London, and the University of Cambridge tested 18,108 DNA changes in the BAP1 gene.
In a process known scientifically as ‘saturation genome editing’, they artificially altered the genetic code of human cells grown in a dish, identifying 5,665 of these changes were harmful.
People carrying these harmful BAP1 variants are over ten per cent more likely to be diagnosed with cancer than the general population.
Writing in the journal, Nature Genetics, the researchers also discovered people with harmful BAP1 variants have elevated levels of IGF-1 in their blood, a hormone linked to both cancer growth and brain development.
Even individuals without cancer showed these elevated levels, suggesting that IGF-1 could be a target for new treatments to slow down or prevent certain cancers, they added.
The discovery also opens the door to developing new drugs that could inhibit these harmful effects, potentially slowing down or preventing the progression of certain cancers, they said.
Detecting these variants early through genetic screening can also guide preventative measures and enhance treatment effectiveness.
Dr David Adams, senior author of the study at the Wellcome Sanger Institute, said: ‘We want to ensure that life-saving genetic insights are accessible and relevant to all people, regardless of their ancestry.
‘Our aim is to apply this technique to a wider range of genes, potentially covering the entire human genome in the next decade with the Atlas of Variant Effects.’
The BAP1 protein acts as a powerful tumour suppressor in the body, protecting against cancers of the eye, lung lining, brain, skin, and kidney.
Inherited variants that disrupt the protein can increase someone’s risk of developing these cancers by up to 50 per cent.
Most of the BAP1-related cancers tend to be more aggressive and triggered earlier in life, research shows.
At the same time, several studies have reported that patients with a BAP1 mutation have an overall survival rate that is seven times longer than those without a genetic predisposition.
