In a recent study, scientists have found over 5,000 genetic variations that allow some cancers to grow. Along with these they also found a possible therapeutic target for treating or even preventing these cancers from arising. The study was published in Nature Genetics and was conducted by researchers from the Wellcome Sanger Institute, The Institute of Cancer Research, London and the University of Cambridge.

They analysed the health effects of genetic alterations in BAP1, a ‘tumour defence’ gene. They discovered that almost one-fifth of these potential mutations were pathogenic, considerably raising the likelihood of developing malignancies of the eye, lung lining, brain, skin and kidney.

Scientists say that the findings benefit individuals from diverse ethnic backgrounds, who have historically been underrepresented in genetics research because the study assessed all possible variants.

The researchers also found a link between certain disruptive BAP1 variants and higher levels of IGF-1, a hormone and growth factor. This discovery opens the door to developing new drugs that could inhibit these harmful effects, potentially slowing down or preventing the progression of certain cancers.

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 a person's lifetime risk of developing these cancers by up to 50 percent, typically occurring around middle age.

Detecting these variants early through genetic screening can help in preventative measures and improve treatment effectiveness and the quality of life for individuals affected.

Researchers from the Sanger Institute and their collaborators at The Institute of Cancer Research and the University of Cambridge tested all 18,108 possible DNA changes in the BAP1 gene by artificially altering the genetic code of human cells grown in a dish, in a process known as ‘saturation genome editing’.

They identified that 5,665 of these changes were harmful and affected the protein’s protective effects. Analysis of UK Biobank data confirmed that individuals carrying these harmful BAP1 variants are over ten per cent more likely to be diagnosed with cancer than the general population.

The team also discovered that people with harmful BAP1 variants have elevated levels of IGF-1 in their blood which is 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.

Further analysis revealed harmful BAP1 variants and higher IGF-1 levels were linked to worse outcomes in uveal melanoma patients, highlighting the potential for IGF-1 inhibitors in cancer therapy.

Dr Andrew Waters, the first author of the study at the Wellcome Sanger Institute, said, “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 variation4. This opens up new possibilities for understanding how these changes drive disease.”

Professor Clare Turnbull, clinical lead of the study, Professor of Translational Cancer Genetics at The Institute of Cancer Research, 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.”