Cancer Research UK scientists have isolated five regions of the genome containing genes which can increase a woman’s risk of developing breast cancer, reveals a major international study published online in Nature* today (Sunday).

The Cambridge based scientists led an international team of researchers in the world’s first large-scale ‘whole genome search’ for faulty genes that increase breast cancer risk. They studied the DNA – the genetic material that makes us unique – in nearly 50,000 women.

Two of the genetic regions they identified contain genes that are thought to increase breast cancer risk by about 20 per cent in women who carry one faulty copy of a gene and by between 40 and 60 per cent if they carry two faulty copies. The lifetime risk for women who carry two faulty copies in either of these two genes would rise from one in 11 to around one in six or one in seven, respectively.

The increased risks incurred by these genetic faults are relatively small and would currently not be suitable for genetic testing. But as more of these ‘low risk’ genes are found, it may be possible to design tests for a combination of genes. This could help doctors make decisions about prevention, diagnosis and treatment for women who inherit faults in one or more of these genes.

Around half of the women in the study were breast cancer patients, and half were healthy women from the general population. The researchers found five regions of DNA that were present more often in the breast cancer patients than the healthy group, suggesting the genes situated within or close to these regions may be the cause of their inherited breast cancer risk.

Study author Professor Douglas Easton, director of Cancer Research UK’s Genetic Epidemiology Unit in Cambridge, said: “We’re very excited by these results because the regions we identified don’t contain previously known inherited cancer genes. This opens the door to new research directions. Only very recent advances in technology have allowed us to carry out such a large comparison study.”

Two of the genes the researchers homed in on are relatively common among the general population. Between one in six and one in 16 women are thought to carry two faulty copies of one of these genes. The genes present in the three other regions identified in the study are also common among the population but carry a lower risk.

In contrast, faults in the well known breast cancer genes BRCA1 and BRCA2 are relatively rare among the population, but put women who carry them at a very high risk of developing breast cancer.

Breast cancer is the most common cancer among women in the UK with 44,000 new cases diagnosed each year. Breast cancer that is caused by inherited genetic faults is thought to account for around five to ten per cent of all cases of the disease. However, the genes identified so far only account for a quarter of cases of inherited breast cancer.

Professor Easton added: “We still don’t know which genes cause 75 per cent of inherited breast cancer cases. This study pinpoints regions containing genes that are responsible for another four per cent. Now we know these search methods are effective, we think that many more breast cancer genes can be found. These methods are also being applied by Cancer Research UK to find genes for a whole range of other cancers, including prostate, bowel and lung cancer.”

The researchers used a three-step approach. First they studied more than 200,000 ‘tags’ – distinct blocks of DNA that act as ‘signposts’ for genes – in 800 patients and healthy people. Then they narrowed the search to 11,000 tags, but studied more women (8,000 in total). They chose these tags because they were more common among the breast cancer patients than among the healthy group in the first stage of the study.

Finally they selected just 30 of the most common tags among the breast cancer patients and looked at them more closely in an extremely large number of women – over 40,000. Five of these tags were found to be more common among the breast cancer patients than the healthy women. These tags ‘signposted’ researchers to four genes they think are responsible for the increased breast cancer risk among the patients they studied.

Lead author Professor Bruce Ponder, Director of Cancer Research UK’s Cambridge Research Institute at the University of Cambridge, said: “Previously scientists have had to search for new cancer genes one at a time, but we have been able to search two thirds of the genome in one go. Rather than fish for new genes one at a time with a rod and line, we have trawled the pool. This is not only a more efficient approach, it gets round the bias of previous studies in which scientists only examined genes they already knew something about.

“At the moment we don’t know how these genes interact with each other or with lifestyle factors, each of which might increase the risk. We’ll continue to search for more genes, but we’ll also focus on unravelling this information so that we’re ready to offer advice to women who may carry one or more of these faulty genes in the future.”

Harpal Kumar, Cancer Research UK’s chief executive, said: “This is an outstanding discovery. Thanks to the international collaboration of more than 15 research teams, this is the first study in the world to demonstrate that by searching the whole genome it’s possible to discover new genes that can increase breast cancer risk.

“These findings will open doors for cancer researchers across the globe to unearth even more genes linked to cancer and ultimately this will benefit patients. Understanding more about what causes breast cancer will help doctors in the future identify and better manage more women at increased risk of the disease.”


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* “A genome-wide association study identifies multiple novel breast cancer susceptibility loci” Douglas F Easton et al. 2007. Nature.

Breast cancer genes

Rare, high-risk genes

BRCA1, BRCA2 – out of every 100 women with a faulty copy of one of these genes, between 50 and 85 will develop breast cancer at some point in their lives (50-85 per cent lifetime risk). Tests for these genes are available to women with cancer and their families if a history of several breast and/or ovarian cancers run in the family.

TP53, PTEN – these genes are rare compared to BRCA1 and BRCA2 but tests are also available for these genes in genetics clinics.

Rare, low-risk genes

CHEK2, ATM, BRIP1, PALB2 – less than one per cent of the population carry a faulty copy of one of these rare genes. Not all women with these genetic faults will go on to develop breast cancer but researchers believe these particular genetic faults each contribute to around 100 cases of breast cancer diagnosed in the UK each year. There are currently no tests available to screen women for these genes.

Common, low-risk genes

CASP8 – this was the only common low-risk gene identified before this study. Around one in 50 women carries two faulty copies of this gene.

This study found:

  • FGFR2 – around one in six women carries two faulty copies of this gene and researchers are sure this gene contributes to inherited breast cancer risk.
  • TNRCP, MAP3K1, LSP1, 8q – these genes were all located close to the regions where the researchers identified the genetic variations.
    • TNRC9 – around one in 16 women carries two faulty copies of this gene.
    • MAP3K1 – around one in 13 women carries two faulty copies of this gene.
    • LSP1 – around one in 11 women carries two faulty copies of this gene.
    • 8q region – the researchers think that a gene exists within this region that contributes to breast cancer risk but they haven’t isolated a specific gene yet.

Genetic predisposition to cancer

Some people are born with a fault in one of their genes. This does not mean that they will actually develop cancer, but it does mean that fewer other things need to go wrong for disease to develop. Doctors say people with a fault in certain genes are more likely to get cancer or have a genetic predisposition to the disease.

Women who have a very strong family history may have a faulty gene or genes in their family that increases their risk of breast cancer. There are number of faulty genes that have been shown to increase breast cancer risk. But, so far, doctors only test for four genes BRCA1, BRCA2, TP53 and PTEN, as these are associated with high risks of developing cancer. For more information about breast cancer risk visit our patient information website CancerHelp UK.

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