A recent study, published in the European Journal of Human Genetics, traced a pathogenic variant in the BRCA1 gene to the Orkney Islands, an isolated population in the Northern Isles of Scotland. Researchers discovered the pathogenic variant V1736A in multiple breast and ovarian cancer families from the Orkney Islands during routine clinical care. This finding prompted further investigation into the prevalence and potential clinical implications of the variant in the Orkney population.
Small islands, big impact
Pathogenic variants in the BRCA1 gene are associated with a high lifetime risk of breast and ovarian cancer. Genetic testing for these variants is widely available, and predictive testing of unaffected family members is common practice. In isolated populations, pathogenic variants can become widespread and contribute significantly to the overall disease burden. The Orkney Islands have the most divergent and isolated population in the British Isles and Ireland.
The study used data from the Orkney Complex Disease Study (ORCADES) and the UK Biobank, both containing genetic and health information from large cohorts of participants. The NHS Grampian genetics team observed the BRCA1 missense variant V1736A in a number of breast and ovarian cancer cases from Orkney. In vitro studies suggested that the variant disrupts BRCA1 activity, and independent evidence for pathogenicity came from saturation genome editing of BRCA1 exons in cultured cells. This led to the reclassification of V1736A from a variant of unknown significance to likely pathogenic. These findings highlight the importance of studying isolated populations to understand the prevalence and impact of pathogenic variants.
“In a person here on this island hundreds of years ago this variation happened in a BRCA1 gene and now we are finding many descendants both in Westray and further afield in Scotland and beyond,” said James Wilson, a co-author of the study. “I think this is the most significant thing that I have ever really discovered. Its going to have immediate benefit to society at large.”
Another NHS genomics success story
Identifying the pathogenic variant V1736A in the BRCA1 gene in the isolated population of the Orkney Islands was the result of routine clinical care by the NHS Grampian Clinical Genetics service. This work highlights the importance of studying isolated populations to understand the impact of pathogenic variants. Professor Zosia Miedzybrodzka, director of NHS North of Scotland Genetic Service said “There are many complex factors, and some people with gene alterations will not get cancer. However, we know that testing and the right follow-up can save lives.”
This is another example of how the use of genomic medicine and screening are having a real impact on patients. By identifying pathogenic variants, healthcare providers can provide personalized care and interventions to reduce the risk of disease and improve health outcomes. The availability of genetic testing and counselling services through the NHS has allowed patients to make informed decisions about their healthcare and empowered healthcare providers to deliver targeted interventions. These advancements have led to improved patient outcomes and have transformed the way healthcare is delivered. It appears the genomics healthcare revolution is in full swing.