Two founder variants account for 90% of pathogenic BRCA alleles in Orkney and Shetland

Viking Genes volunteer data has linked a harmful variant in the gene BRCA2, which increases the chance of developing breast, ovarian and prostate cancers, to a historic origin in Whalsay, Shetland. This follows previous observations for the origin of a BRCA1 founder variant from the isle of Westray in Orkney.

The Viking Genes research team has found that one in 40 people who have four grandparents from Whalsay, one of the isles of Shetland, share the same variant in the BRCA2 gene. The variant increases the chance of developing breast, ovarian and prostate cancers.  It is six times more common in Whalsay descendants than BRCA1 and BRCA2 gene variants are in the UK mainland population.

Most breast, ovarian and prostate cancers start due to chance damage. However, some people inherit a variant in a gene which increases their chance developing cancer.  BRCA2 works in this way.

VIKING Genes found a BRCA2 variant called the c.517-2A>G variant in 9 of the 2,000 volunteers with three or more Shetlandic grandparents.

This variant had already been seen by the NHS Grampian genetics team in families in Shetland with breast, ovarian and prostate cancer.

VIKING DNA testing and genealogy research linked the origin of the variant to a founder from Whalsay. This is like our previous observations for the origin of a BRCA1 founder variant from the isle of Westray in Orkney.

Whalsay pedigree

It is very important to understand that just two gene variants account for nearly all (>90%) of the inherited cancer risk from BRCA variants in Orkney and Shetland. This is in stark contrast to the situation in the general UK population, where 369 variants would need to be tested to account for the same proportion of cancer risk from BRCA genes. Any future screening programme for the Northern Isles should therefore be very cost-effective, like the NHS England Jewish screening programme.

Professor Jim Flett Wilson Chair of Human Genetics, University of Edinburgh

Developing cancer is not solely down to carrying the BRCA2 variant, there are many complex factors, and some people with the gene variant will not get cancer. However, we know that testing and the right follow-up can save lives. Many people who carry a gene variant are unaware of it. Biological relatives of people with the BRCA2 variant are encouraged to consider being tested.

Professor Zosia Miedzybrodzka Chair of Medical Genetics (University of Aberdeen), Director of the NHS North of Scotland Genetic Service

Women with the BRCA2 variant are offered MRI breast screening, usually from age 30. Some also choose prophylactic breast and ovarian surgery to significantly reduce risks. Men with BRCA2 are advised to have annual PSA blood tests from the age of 40.

An NHS Grampian genetics pilot recently demonstrated feasibility of community-based BRCA1 testing in Westray. The pilot was funded by the Westray Development Trust and funding for a wider roll out is currently being sought. It is hoped more testing for the Whalsay BRCA2 variant could similarly become available if funding can be secured to enable targeted community screening.  

Everyone in the VIKING I and VIKING II studies who asked for genetic results feedback and who have this Whalsay BRCA2 variant have already been sent a letter.

Comprehensive testing for all BRCA1/2 variants is already standard NHS care for everyone who develops ovarian cancer, and also those with breast cancer under 40 and prostate cancer under 50, and in some other circumstances.

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