Over 5,000 high-risk cancer variants identified in study of 'tumour protection gene'

A startling new study has identified thousands of genetic mutations that could amplify the risk of cancer, pinpointing malfunctions in the "tumour protection gene" BAP1.

In a groundbreaking revelation, researchers have unearthed over 5,000 genetic alterations that may compromise the BAP1 gene, a critical tumour suppressor that shields against various cancers including those affecting the eye, lung lining, brain, skin, and kidney.

For years, the scientific community has recognised the role of BAP1 in curbing cancer growth, but the specific genetic changes leading to increased cancer risk remained elusive.

Now, British scientists have shed light on these harmful mutations that can thwart BAP1's protective functions.

Carrying certain inherited variants of this gene could heighten an individual's risk of developing specific cancers by up to 50% as they approach middle age.

As a result of the study, genetic screening for early detection could pave the way for proactive prevention.

The research also highlighted a fifth of these genetic defects are attributable to pathogens like viruses, which markedly raise the likelihood of contracting cancers of the eye, brain, skin, and kidney.

Published in Nature Genetics, the results of this study could expedite diagnosis and connect patients with targeted treatments more swiftly. It could also spur the development of new drugs to prevent or slow down the progression of certain findings.

The findings are freely available, meaning doctors can utilise them immediately.

The research was conducted by scientists from the Sanger Institute, in collaboration with The Institute of Cancer Research and the University of Cambridge. They tested 18,108 potential DNA changes in the BAP1 gene by artificially altering the genetic code.

A total of 5,665 harmful changes were identified that disrupted the protein's protective effects. When these results were compared against UK Biobank data, it was confirmed that individuals with these harmful variants were over 10% more likely to be diagnosed with cancer.

Furthermore, it was found that people with these harmful variants also had elevated levels of IGF-1 in their blood. This hormone has previously been associated with 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. Dr Andrew Waters, the first author of the study, noted that the approach used in the study "provides a true picture of gene behaviour", opening up more possibilities for future insights into the gene, its changes, and the impact these have on cancer.

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