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Last Updated: Aug 19th, 2006 - 22:18:38

Breast Channel
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Latest Research : Cancer : Breast

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ATM Gene Fault Doubles Breast Cancer Risk
Jul 10, 2006, 19:19, Reviewed by: Dr. Priya Saxena

“This is a significant study. Pinpointing genes that raise the risk of breast cancer will help us to gain a much clearer understanding of how the disease develops."

 
The risk of developing breast cancer is doubled in women who inherit a damaged version of a gene called ATM, according to a study published by Cancer Research UK funded scientists and collaborators in Nature Genetics today (Monday).

A team of researchers at The Institute of Cancer Research compared 433 breast cancer patients with a family history of the disease, but who don’t carry faults in the breast cancer genes BRCA1 or BRCA2, with 521 healthy women. They found 12 ATM gene faults in the patient group, compared with two in the healthy group, showing that the gene is linked to breast cancer more often than would be expected by chance.

The team conducted a detailed statistical analysis of their data and estimated that carrying a faulty version of the ATM gene raises a woman’s risk of breast cancer by about two-fold. This takes the overall risk of breast cancer by age 70 in a carrier of the faulty gene from one in twelve to around one in six. These findings could lead to new ways of identifying women at increased risk of developing breast cancer and in treating and preventing the disease, but further research will need to be done first.

Around five to ten per cent of breast cancers are believed to be due to inherited genetic faults. Some of these are well known, such as faults in the BRCA genes, but most of the genes involved in familial breast cancer have not yet been identified. For over 20 years scientists have reported links between breast cancer and the ATM gene, but until now, there was controversy about which faults in ATM could increase the risk of breast cancer and by how much.

Study author Nazneen Rahman, professor of cancer genetics at The Institute of Cancer Research, said: “Our study provides strong evidence for the first time that damaged ATM genes definitely have a moderate effect on breast cancer risk in a small number of women. Women who carry these genetic faults could benefit from targeted screening and new treatments in the future, but we need to learn much more about ATM before this information will feed into clinical practice.”

Serious faults in the ATM gene are responsible for a rare, progressive, childhood disease, called ataxia-telangiectasia, which leads to severe neurological disability, as well as blood cancers and respiratory problems. People with this disorder have two faulty copies of the ATM gene, and carriers of the disease have one. It is the carriers with one faulty copy of the gene who have the higher breast cancer risk, although they are otherwise healthy.

ATM, like BRCA1 and BRCA2, is a DNA-repair gene, so women with a faulty ATM gene cannot repair damaged DNA correctly. Cells with damaged DNA can start to replicate uncontrollably and become cancer cells, which is why individuals with faulty DNA repair genes are at an increased risk of cancers, such as breast cancer.

About 150 families in the UK have members with two faulty copies of the ATM gene who are affected by ataxia-telangiectasia. Between half to one percent of the general population carry a single faulty copy of the gene. This means around 400 of the women who develop breast cancer each year in the UK are thought to carry an ATM gene fault – less than one per cent of the 41,000 breast cancer cases.

Professor Michael Stratton, from The Institute of Cancer Research and The Wellcome Trust Sanger Institute, who also worked on this study and who led the team that discovered BRCA2, said: “Inherited risk of breast cancer is probably caused by a combination of genes, so our work is now focused on finding out what other genetic factors are at play that cause around 15 per cent of female ATM carriers to go on to develop breast cancer.”

Professor John Toy, medical director at Cancer Research UK, said: “This is a significant study. Pinpointing genes that raise the risk of breast cancer will help us to gain a much clearer understanding of how the disease develops. Also by identifying individuals who could benefit from specific treatments, scientists can begin to develop drugs that could help these patients in the future. An example is a new class of anti-cancer drugs currently being developed by Cancer Research UK scientists to exploit this defect in DNA repair.”

The relative risk of breast cancer associated with ATM mutations was estimated to be 2.37 (two fold). This is similar to the increase in risk seen with the CHEK2 gene, which was reported by the same group of researchers in 2002.

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

Women who have a very strong family history may have a faulty gene in their family that increases their risk of breast cancer. There are several genes faults that can increase breast cancer risk. But, so far, doctors can only test for two of them, BRCA1 and BRCA2.
 

- ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Renwick et al. (2006). Nature Genetics.
 

www.cancerresearchuk.org

 
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This research was supported by Cancer Research UK, The Institute of Cancer Research and Breast Cancer Campaign.

The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. Website at: www.icr.ac.uk.

The Institute works in a unique partnership with The Royal Marsden NHS Foundation Trust, forming the largest Comprehensive Cancer Centre in Europe. This relationship enables close daily contact with those on the frontline in the fight against cancer - the clinicians, the carers and most importantly, the patients.

The Institute is a charity that relies on voluntary income. The Institute is one of the world’s most cost-effective major cancer research organisations with over 90p in every £ directly supporting research.


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