Cancer Research UK scientists have identified a DNA region which can increase or decrease the high breast cancer risk associated with the BRCA1 gene. The region is particularly involved in oestrogen receptor negative breast cancer and has also been linked to an increased risk of ovarian cancer in the general population.

The research is published in Nature Genetics today (Sunday) alongside two other independent studies linking this region and four others to ovarian cancer.

Two independent research groups identified the same region after carrying out genome-wide association studies*. Researchers led by Dr Antonis Antoniou based at the Cancer Research UK Centre for Cancer Genetic Epidemiology at the University of Cambridge, identified the region after searching through the genomes of more than 2,300 women with faults in the BRCA1 gene, to find other sections of DNA which could alter breast cancer risk.

Meanwhile researchers led by Dr Simon Gayther, based at the Cancer Research UK Genetic Epidemiology Unit, at the University of Cambridge and UCL (University College London), pinpointed the same region after carrying out a similar study looking at nearly 9,000 women with ovarian cancer from the general population.

On average, around 65 per cent of women carrying a faulty BRCA1 gene will develop breast cancer – and around 40 per cent ovarian cancer – by the age of 70.

These studies reveal that if a woman with a BRCA1 fault also carries the risk ‘version’ of the 19p13 region, her breast cancer risk may be higher still.

Dr Antonis Antoniou, lead author on the breast cancer study and scientist at the Cancer Research UK Centre for Cancer Genetic Epidemiology, University of Cambridge, said: “We’ve found a DNA region that acts like a volume control – to turn up or down the risk of developing breast cancer from faults in the BRCA1 gene.

“Our discovery is the first step in a much larger study to identify genetic factors that modify breast cancer risk in women carrying BRCA1 mutations, and ultimately could help assess the risk for each woman and monitor for the disease.”

The same DNA stretch was also associated with the risk of developing oestrogen receptor negative breast cancer in women without a faulty BRCA1 gene, and also associated with the risk of developing triple negative breast cancer – oestrogen, progesterone and HER2-negative breast cancer.

In a separate study in Nature Genetics today, the same region was also shown to increase the risk, to a lesser degree, of ovarian cancer in women who don’t carry a BRCA1 fault.

Dr Simon Gayther at UCL, who is lead author on this study and whose work is supported by Cancer Research UK and the Eve Appeal, said: “Our study showed that the same genetic region also plays a role in ovarian cancer, suggesting that it is involved in the same faulty pathway.

”This is important because it suggests that women who carry certain versions of this DNA stretch could benefit from closer monitoring for both breast and ovarian cancers.”

Dr Andrew Berchuck, head of the international Ovarian Cancer Association Consortium (OCAC) steering committee and an author on the study, said: “The critical validation of these findings was performed by large consortia of investigators from around the world, and this research represents a triumph of science without borders for the benefit of all women.”

A third study, led by Dr Paul Pharoah, also at the Cancer Research UK, Centre for Cancer Genetic Epidemiology at the University of Cambridge and UCL, and published in the same journal today, reveals four other separate genetic regions also associated with ovarian cancer risk in the general population.

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “We’re dedicated to unravelling cancer risk so we can provide doctors with better tools to identify who is at risk and help select the best treatment.

“This research provides evidence that by carrying out genome wide association studies in certain subgroups – such as people with BRCA1 mutations – we can identify other breast and ovarian cancer risk factors which have previously been missed.”


For media enquiries please contact the Cancer Research UK press office on 020 7061 8309 or, out-of-hours, the duty press officer on 07050 264 059.


Antoniou A. et al., A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population (2010), Nature Genetics.

Bolton K. et al., A genome-wide association study of survival in ovarian cancer identifies a locus at chromosome 19 that is associated with susceptibility to ovarian cancer (2010), Nature Genetics.

Goode E. et al., Identification of four novel ovarian cancer susceptibility loci identified in a genome-wide association study (2010), Nature Genetics.


* Stage 1 of the study involved screening more than 500,000 markers in the genome for their associations with breast cancer risk for BRCA1 mutation carriers. This paper investigated in more detail the 100 most promising markers in a large group of the population carrying the faulty BRCA1 gene. A large scale replication stage is also ongoing in which thousands of markers will be investigated in detail.

Oestrogen and breast cancer

Breast cancer can be oestrogen positive (ER positive) – in which case it is driven by the hormone oestrogen attaching to oestrogen receptors on the breast cancer cells. These tumours are normally treated with hormonal therapy such as tamoxifen. If a breast cancer involves cells which do not have oestrogen receptors – it is ER negative – patients will usually be advised to have chemotherapy.


  • Around 1 in 800 women in the UK carry a faulty BRCA1 gene and 1 in 500 carry a faulty BRCA2 gene.
  • Women carrying the BRCA1 and BRCA2 mutation have a 45-65 per cent chance of developing breast cancer, and a 20-45 per cent chance of developing ovarian cancer, by the age of 70.
  • Risks in carriers of genetic faults vary substantially and understanding these differences can potentially lead to better understanding of an individual’s risk, with implications for the clinical management of these individuals.
  • BRCA1 breast tumours have distinct characteristics compared with the large majority of tumours in the general population.
  • Genetic testing for faulty BRCA genes is available on the NHS for women with a very strong family history.

The study was coordinated jointly in Cambridge funded by Cancer Research UK and Mayo clinic (USA).

The BRCA1 study involved 39 research groups from Europe, North America and Australia participating in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) coordinated in Cambridge and funded by Cancer Research UK.

About Cancer Research UK

  • Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.
  • Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.
  • Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.
  • Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.
  • Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.

For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7121 6699 or visit

About the University of Cambridge

The University of Cambridge’s reputation for excellence is known worldwide and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the world’s most significant scientific breakthroughs have occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history’s greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.

About UCL

Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. UCL is the fourth-ranked university in the 2010 QS World University Rankings. UCL alumni include Marie Stopes, Jonathan Dimbleby, Lord Woolf, Alexander Graham Bell, and members of the band Coldplay. UCL currently has over 12,000 undergraduate and 8,000 postgraduate students. Its annual income is over £600 million.

About The Eve Appeal

The Eve Appeal fundraises for the vital research into ovarian cancer undertaken by the Gynaecological Cancer Research Centre at UCL, and funded Dr Gayther’s team and the UKOPS population study elements of this Genome Wide Association Study work to a total in excess of £850,000.
For further information or to support the work of The Eve Appeal please call 0207 299 4430 or visit

About the Ovarian Cancer Association Consortium (OCAC)

The Ovarian Cancer Association Consortium (OCAC) was founded in 2005 and its activities are supported by the Ovarian Cancer Research Fund (OCRF) in New York City ( OCAC comprises over twenty groups of investigators from around the world who are conducting genetic epidemiology studies of ovarian cancer. The group meets biannually and is working together to discover common genetic polymorphisms that affect a woman’s risk of developing ovarian cancer.
The ability to inform women whether they are more or less likely to develop the disease is an important first step towards an indivualised approach to decreasing ovarian cancer deaths. Those at increased risk due to genetic factors, as well as reproductive risk factors such as not having had children or used oral contraceptives, would be the best candidates for screening and prevention strategies. This potentially includes interventions such as screening with CA125 and/or ultrasound, as is being examined in the randomised UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Other approaches include prophylactic removal of the ovaries and fallopian tubes or chemoprevention with oral contraceptives.