Cancer risk gene variant discovered in Orkney
Orkney Complex Disease Study (ORCADES) volunteer data has helped to link a variant in the gene BRCA1 to a historic origin in Westray, Orkney
Around one in 1000 women across the UK have a BRCA1 variant that gives them an increased chance of developing breast cancer and ovarian cancer.
In contrast, one in 100 people who have grandparents from Orkney have a founder gene variant that causes a higher than average lifetime risk of developing breast and ovarian cancer.
Most breast and ovarian cancers happen due to chance. However, some cases are caused in part by inherited gene alterations, which increase the chances that a woman will get one or both of these conditions. One of the most common of these predisposing genes is BRCA1.
The Orkney Complex Disease Study (ORCADES), which is part of Viking Genes, is led by Professor Jim Flett Wilson. Viking Genes is part of the Quantitative Traits in Health and Disease programme, funded by the Medical Research Council, at the MRC Human Genetics Unit.
The fact that one in a hundred Orcadian women carry a high-risk variant for breast and ovarian cancer highlights the value of population studies such as Viking Genes, without which we would not know this. It is imperative that Scottish island populations are represented in research, to allow equitable delivery of genomic medicine across the country.
Historic origin linked to Westray, Orkney
Over many years, the Orkney NHS genetics clinic team, led by the University of Aberdeen’s Professor Zosia Miedzybrodzka, found the same specific variant in the BRCA1 gene repeatedly in women from Orkney with breast and / or ovarian cancer. The genetics team used clinical genealogy to show that the patients with the variant linked into one large family tree with an origin in the Orkney outer isle of Westray.
When the ORCADES (Viking Genes) team examined genetic data from more than 2000 volunteers, men and women with three or more Orkney grandparents, they found this BRCA1 “V1736A” variant present in the DNA of 1% of the volunteers. Many of the ORCADES participants with the variant are not closely related to branches of the family identified in the clinic, but all share historic Westray ancestors.
Professor Zosia Miedzybrodzka is director of the NHS Grampian Clinical Genetics service and Independent Genetic Advisor to the Viking Genes study, and has also run the Orkney genetic clinic for over 20 years.
Developing cancer is not solely down to carrying the BRCA1 mutation alone, 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. Many people who have the gene alteration are unaware of it. In the long run we want to make a test available to women who want to know if they have the gene. As it is hereditary, the gene variant can affect multiple members of families. Risk-reducing surgery, breast screening with MRI and lifestyle advice can all improve health for women with the gene. Men do not need to take any particular action for themselves, but they can pass the gene onto their descendants.
The NHS Grampian genetic clinic is running a helpline for queries about breast and ovarian cancer in Orkney. The number to call is 01224 553940. Queries can also be directed by email to gram.orkBRCAgene@nhs.scot.
This paper was published in the European Journal of Human Genetics. To read more visit:
Clinical case study meets population cohort: identification of a BRCA1 pathogenic founder variant in Orcadians
Frequently Asked Questions - BRCA1 and Orkney
What does the latest study mean for people with Orkney ancestry?
A study has found that 1 in 100 people (1%) who have grandparents from Orkney have a gene alteration that causes women a higher change of developing breast and/or ovarian cancer.
Over many years, the Orkney genetics clinic team identified the same specific single variant in the BRCA1 gene repeatedly in women from Orkney with breast and/or ovarian cancer. Prof Zosia Miedzybrodzka from the NHS Orkney genetic clinic worked with Prof Jim Wilson’s ORCADES and VIKING studies to see how common the gene is and where it came from. They found that almost all the people with the gene alteration share historic Westray ancestors.
How does BRCA1 link to cancer?
We have two copies of most of the genes in our body – one from our mother and one from our father. Most breast and ovarian cancers are caused by chance damage to both copies of one of a number of genes in a cell of the breast or ovary.
However, some women inherit an alteration in one copy of a gene in all of their cells. This increases the chances that both copies of one of those key genes get damaged and go on to cause breast or ovarian cancer.
One of the commonest of these predisposing genes is BRCA1. Around one in 1000 women across the UK have a BRCA1 gene alteration that gives them a high lifetime chance of developing breast cancer and ovarian cancer.
How are people with BRCA1 looked after?
Risk-reducing surgery or breast screening using MRI from age 30 and lifestyle advice can all improve health for women with the gene. Men with the gene do not have a big increased chance of getting breast cancer but can pass the gene onto their children.
Who can be tested for the gene right now?
A test is currently available to people with Orkney born grandparents who (1) know of a direct family connection to the gene, or (2) have a close history of ovarian or breast cancer in their family.
Are there plans to expand the availability of testing?
Planning is now underway for a small pilot trial, organised by NHS Grampian and supported by local cancer charity Friends of ANCHOR, that will offer testing for the gene variant to anyone living in Westray with a Westray-born grandparent, regardless of a family history. Further work is being done with the Westray community to explore the latest findings and if the pilot is successful, the long-term aim is to offer the test to anyone in Scotland with a Westray-born grandparent who wants it.
I took part in ORCADES and want to know if the study found I have the BRCA1 gene change. How can I find out?
You can get in touch with Viking Genes at firstname.lastname@example.org for more information.
Where can I find more information?
NHS Grampian is running a helpline for queries about the gene variant linked to breast and ovarian cancer for those who have grandparents from Orkney. The number to call is 01224 553940. Email enquiries can be directed to gram.orkBRCAgene@nhs.scot. GPs will not be able to assist with gene testing and any questions about this research and next steps should be directed to the helpline.
More information on BRCA1 and breast and ovarian cancer in families is available via the NHS and MacMillan Cancer Support. Cancer support and advice is available from CLAN and Friends of Anchor can also provide practical and emotional support.
Information about cancer symptoms and how to reduce your chances of getting cancer is available from the NHS Inform website. People worried that they might have cancer should read the advice on NHS Inform and consult their GP.