Survey of cancer genes uncovers Viking roots

The Scots and Northern Irish are genetically distinct from elsewhere in the UK, with a different legacy of inherited cancers than in England and Wales, the largest ever survey of its kind reveals.

Researchers from across Scotland and Northern Ireland, funded by Cancer Research UK, the Medical Research Council, the Scottish Executive and the Breast Cancer Campaign, tracked down families with inherited breast and ovarian cancer and examined the genetic faults responsible.

The study, published in today’s British Journal of Cancer¹, found women from Scotland and Northern Ireland with breast cancer in their families have inherited a distinct cluster of genetic mutations, including one that may have been brought over by the Vikings. The results could help doctors improve genetic testing and counselling for affected women in the two countries.

Inheriting damaged versions of two key genes – called BRCA1 and BRCA2 – causes around three per cent of breast cancers, many ovarian cancers and several other types of the disease.

But women can be born with a wide variety of faults in these genes, some giving them a higher risk of developing cancer than others. Knowing which genetic faults are likely to occur is crucial for efficient genetic testing and accurate advice on the risk of developing cancer – vital if women are to take difficult decisions such as the choice to have breasts or ovaries removed.

Researchers studied BRCA mutations in the closely related Scottish and Northern Irish populations by tracking families visiting genetics clinics in Edinburgh, Glasgow, Aberdeen, Dundee and Belfast. They found 107 families – accounting for nearly 400 cases of breast cancer and 150 cases of ovarian cancer – and sequenced their BRCA genes to identify the inherited faults.

Just 10 types of genetic damage, five in each gene, accounted for almost half of all the mutations detected, a much narrower spread than in England or Wales. This reflects the common ancestry and close-knit populations in Scotland and Northern Ireland.

Two genetic faults – the 2800 delAA mutation in the BRCA1 gene and the 6503 delTT mutation in BRCA2 – were particularly common, accounting for a quarter of all mutations. The first of these is likely to have originated in West-Central Scotland or Ireland, while the second was especially common in the Aberdeen and Dundee clinics and may have been brought over by Viking raiders or Scandinavian fishermen.

Researcher Professor Mike Steel of the University of St Andrews, funded by the Breast Cancer Campaign and the Scottish Executive, says: “It looks like the original Scottish and Northern Irish population was founded by quite a small group of people with certain characteristic genes and less genetic variety than elsewhere. Today that genetic legacy continues to affect predisposition to inherited cancers and the way they are diagnosed and treated.”

Fellow researcher Dr Marie Boyd, of the Cancer Research UK Beatson Laboratories, adds: “Scotland seems to have its own distinctive cluster of cancer mutations, some originating here and others perhaps brought over by invaders.

“Knowing which genetic faults we can expect to find will make genetic testing and counselling much easier, helping genetics clinics to improve the service they provide for Scottish women.”

The BRCA genes are extremely large and identifying cancer-causing mutations is like finding a needle in a haystack. Testing primarily for the 10 most common types of genetic fault would be faster and more practical, allowing doctors to make the genetic test more widely available.

Dr Boyd adds: “Even without the extensive gene sequencing described here, this kind of study will help to identify people who are at risk of breast and ovarian cancer and channel them into the appropriate clinics at younger ages to pick up any abnormalities at an early stage. Such early cancer detection undoubtedly saves lives.”

Scientists also found evidence that specific genetic faults in the Scottish population have a different effect on cancer risk than others. They found that faults in the first two thirds of the BRCA1 gene gave women a significantly higher risk of ovarian cancer than faults in the final third, while damage in the central portion of BRCA2 also conveyed a high risk of the disease. This information should allow doctors to carefully tailor the advice they give to individual women.

Sir Paul Nurse of Cancer Research UK, which owns the British Journal of Cancer, says: “This study gives a fascinating insight into the ancestry of the Scottish and Northern Irish populations, but importantly, it also provides the basis for a more efficient testing procedure for breast cancer genes.

“Women who inherit a gene that gives them a very high risk of developing cancer need to have the best possible support and advice, to help them make difficult decisions about how to preserve their health. By identifying the most common types of cancer mutation, the new findings should further improve the standard of cancer care for women in Scotland and Northern Ireland.”

ENDS

1. British Journal of Cancer88 (8)

Notes to Editor:

Women who inherit a damaged BRCA1 gene have a 60-85 per cent chance of developing breast cancer at some stage in their lives and a 20-40 per cent chance of developing ovarian cancer. For BRCA2, the risks are 40-60 per cent and 10-20 per cent respectively.

Studies of cancer genetics in Scotland are particularly accurate, because the Scottish Cancer Registry is recognised as one of the best in the world.

The Medical Research Council (MRC) is a national organization funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC’s expenditure of over £412 million is invested in its 50 Institutes, Units and Centres, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.