Thousands of High-Risk Cancer Genes Identified in Landmark Study…So Could You Be Carrying Them Without Knowing It?

Scientists could be closer to new cancer treatments after discovering thousands of genetic mutations that increase the risk of the disease.

Experts have long known that many cases are linked to problems with a gene called BAP1, also known as the “tumor protection gene,” which causes it to malfunction and fuel cancer growth.

But until now, they weren't sure exactly what changes they should pay attention to.

British researchers now have an answer after discovering more than 5,000 harmful defects that can disrupt its protective effects.

They also found that about 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 kidneys.

In what could be welcome news for thousands of Britons at risk of the disease, scientists said the discovery could help patients get targeted treatments more quickly and pave the way for the development of new drugs.

Professor Clare Turnbull, cancer genetics expert at the Institute of Cancer Research in London and consultant in clinical cancer genetics at the Royal Marsden NHS Foundation Trust, said: “This research could lead to more accurate interpretation of genetic tests, earlier diagnoses and better outcomes for patients and their families.”

Dr Andrew Waters, an expert in cancer gene mutations at the Wellcome Sanger Institute, added: “Previous approaches to studying how variants affect gene function have been done on a very small scale or have excluded important contexts that may contribute to their behaviour.

“Our approach provides a faithful picture of gene behavior, enabling larger and more complex studies of genetic variation.

“This opens up new possibilities for understanding how these changes cause disease.”

As part of this research, scientists from the Wellcome Sanger Institute, the Institute for Cancer Research, Londonand the University of Cambridge tested 18,108 DNA changes in the BAP1 gene.

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In a process known scientifically as “saturation genome editing,” they artificially altered the genetic code of human cells grown in a petri dish, identifying 5,665 of the edits as harmful.

People carrying these harmful variants of the BAP1 gene have a more than 10% higher risk of being diagnosed with cancer than the general population.

In a paper published in the journal Nature Genetics, the researchers also found that people with harmful variants of the BAP1 gene had high 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 or prevent certain cancers, they added.

The discovery also opens the door to the development of new drugs that could inhibit these harmful effects, potentially slowing or preventing the progression of some cancers, they said.

Early detection of these variants through genetic screening can also guide preventive measures and improve treatment effectiveness.

Dr David Adams, lead author of the study at the Wellcome Sanger Institute, said: “We want to ensure that vital genetic knowledge is accessible and relevant to everyone, regardless of their ancestry.

“Our goal is to apply this technique to a broader range of genes, potentially covering the entire human genome over the next decade with the Atlas of Variant Effects.”

The BAP1 protein acts as a powerful tumor suppressor in the body, protecting against cancers of the eye, lung lining, brain, skin and kidney.

Inherited variants that disrupt the protein can increase the risk of developing these cancers by up to 50%.

Most cancers linked to the BAP1 gene tend to be more aggressive and start earlier in life, research shows.

At the same time, several studies have reported that patients carrying a BAP1 mutation have an overall survival rate seven times longer than those without a genetic predisposition.