BRCA2 variant found in people of Shetland heritage

One in 40 people who have four grandparents from the Isle of Whalsay in Shetland, Scotland, carry a gene variant known to increase their risk of developing cancer.

The frequency and origin of this variant was investigated in a population-based research study of Shetlandic people, led by Professor Jim Wilson from the University of Edinburgh. The study, VIKING I, investigated genetic data from 2000 volunteers with three or more Shetlandic grandparents and found that nine carried the same BRCA2 variant. This variant is six times more common in Whalsay descendants than in the mainland UK population, and correlates with an increased risk of breast, ovarian and prostate cancers.

Professor Wilson told the BBC: 'This BRCA2 variant in Whalsay I think arose prior to 1750. This is why these things become so common in given places because many people descend from a couple quite far back in the past and if they have a cancer variant, then a significant number of people today – five or even ten – generations later will have it.'

Viking Genes, the overarching study that includes VIKING I, aimed to investigate the genetic diversity of people from Orkney and Shetland. Results published last year indicated a single variant in BRAC1 found in one percent of people with three grandparents from the Orkney island of Westray increased their risk of developing breast and ovarian cancer (see BioNews 1183). In a pilot programme, all adults living on the island, who have a grandparent from the island, are being invited to take a test for the gene variant.

'It is very important to understand that just two gene variants account for nearly all (over 90 percent) of the inherited cancer risk from BRCA variants in Orkney and Shetland,' said Professor Wilson. '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.'

Variants in BRCA1 and BRCA2 that increase risk of developing cancer have been identified in isolated populations including those in the Northern Isles of Scotland, as well as Ashkenazi Jews. People with Jewish ancestry are offered genetic testing for these variants through NHS England but are yet to be offered in Scotland (see BioNews 1225).

The NHS currently offers a test to relatives of those with the known BRCA2 variant, as well as genetic risk assessments for those with Whalsay born grandparents and a family history of cancer.

Professor Zosia Miedzybrodzka, from Aberdeen University, who was also involved in the study, said: '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 Wilson told Shetland News that he would like to see policy changes to increase the availability of NHS screening to affected populations. Current fundraising efforts aim to improve availability of screening to populations from Scotland's Isles and their descendants, who are at higher risk of having the BRCA2 variant.

The researchers have published their current findings as a preprint in medRxiv, which has not yet been peer-reviewed.