High-risk cancer genes identified in landmark study exploring faults of ‘tumour protection gene’

Cancer patient
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A groundbreaking study has revealed thousands of gene variants that affect BAP1, commonly known as the tumour protection gene, could increase your risk of cancer. The BAP1 protein is a powerful tumour suppressor protecting against cancers of the eye, lung lining, brain, skin and kidney.

A malfunction in the gene fuels cancer growth and while this has been a well-known fact for a while, scientists weren’t entirely sure what changes or malfunctions to look out for in the gene to indicate a risk of cancer growth. However, British researchers have now divulged their findings after discovering more than 5,000 harmful changes that can interfere with the protective effects of BAP1.

The study also revealed roughly a fifth of these faults were caused by pathogens, viruses for example, that significantly increased the risk of developing the likes of eye, brain, skin and even kidney cancer.

Some inherited variants of the gene can increase a person’s lifetime risk of developing cancers of the eye, lung lining, brain, skin and kidney by up to 50% around middle age. Early detection through genetic screening following the study’s results can guide preventative measures.

Published in Nature Genetics, the results of the study could help diagnose and connect patients with targeted treatments quicker as well as enabling the development of new drugs to prevent or slow down the progression of certain findings. The findings are also freely available meaning it can be used immediately by doctors.

The researchers from the Sanger Institute and collaborators at The Institute of Cancer Research and the University of Cambridge tested 18,108 possible DNA changes in the BAP1 gene by artificially altering the genetic code and identified a total of 5,665 changes that were harmful by disrupting the protein’s protective effects. Comparing these results against UK Biobank data confirmed individuals with these harmful variants were over 10% more likely to be diagnosed with cancer.

Additionally, it was discovered that people with these harmful variants also had elevated levels of IGF-1 in their blood. This hormone has previously been linked to both cancer growth and brain development.

A combination of harmful BAP1 variants and higher IGF-1 levels were also linked to worse outcomes in uveal melanoma patients. First author of the study, Dr Andrew Waters noted that the approach used in the study “provides a true picture of gene behaviour” to open more possibilities for future insights on the gene, its changes and the impact these have on cancer.

Clinical lead of the study, and professor of Translational Cancer Genetics at The Institute of Cancer Research, Professor Clare Turnbull added: “This research could mean more accurate interpretation of genetic tests, earlier diagnoses and improved outcomes for patients and their families.”