Scientists Discover Four New Breast Cancer Genes

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Main Category: Breast Cancer
Also Included In: Genetics
Article Date: 29 May 2007 - 0:00 PDT


A large scale genetic study involving scientists from 15 countries has found four new genes that appear significantly to raise a woman's risk of getting breast cancer.

The study is published in the early online edition of the journal Nature.

The four genes are called FGFR2, TNRC9, MAP3K1 and LSP1.

The study was conducted by scientists from Australia, Denmark, Finland, France, Germany, Korea, The Netherlands, New Zealand, Poland, Singapore, Sweden, Taiwan, Thailand, the UK and the US.

Douglas Easton of the University of Cambridge, UK, who was involved in the research, said that the discovery could help doctors improve their prediction of breast cancer risk and select better treatments to prevent and cure the disease.

But more important, he said, is how these discoveries help researchers find out how the disease works.

"We had no inkling that these genes had anything to do with breast cancer," said Easton.

More than 10 per cent of women in the US and the UK are affected by breast cancer, which is thought to have a significant genetic component. But until this new research, scientists could only account for around 25 per cent of the genetic part of breast cancer risk. They suspected that the residual genetic variance was likely due to a range of different gene mutations.

To look for further mutations that might be linked to breast cancer, Easton and colleagues conducted a two-stage genome-wide association study (GWAS) in nearly 4,400 women with breast cancer and a similar number of controls. They then confirmed 30 suspected single nucleotide polymorphisms (SNPs) in nearly 22,000 women with breast cancer and a similar number of controls spanning 22 studies.

Overall they looked at over 225,000 SNPs and discovered that five in until now unknown loci in the genome showed strong and consistent links with breast cancer incidence. Four of these were found to be the most plausible: FGFR2, TNRC9, MAP3K1 and LSP1. However, they said that there may well be many other mutations that contribute similar significance to breast cancer risk that could be found using their approach.

The gene whose variants appears to confer the greatest risk of the four is fibroblast growth factor receptor 2, or FGFR2.

Women who have two copies of the high risk variants of this gene, estimated to be about 16 per cent of the female population, have a 60 per cent greater chance of getting breast cancer compared with women who have none, said Easton and colleagues.

These discoveries alone are not enough to enable doctors to scan a woman's genes and tell her what her breast cancer risk is likely to be. But, as more such studies are conducted and more risk factors revealed, the more realistic such a scenario becomes.

"As more genes are identified, tests will become more predictive," said Easton.

"I wouldn't be at all surprised if there were dozens or hundred of genes involved," he added.

Easton believes a similar approach will work for other cancers, and he is now studying prostate cancer.

Two other studies, reported in Nature Genetics, have also discovered genetic variants that appear to increase the risk of breast cancer.

One study conducted in the US and led by David J Hunter of the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusett, is also a genome-wide association study (GWAS). This GWAS examined around 2,000 postmenopausal women and 2,000 controls and found several genetic variants in the FGFR2 gene associated with increased risk of breast cancer.

And in the other study, led by Simon N Stacey of deCODE genetics, Reykjavik, Iceland, an international team of scientists found mutations on chromosomes 2 and 16 that appear to increase the risk of estrogen receptor-positive breast cancer. Overall they studied over 4,500 affected Icelandic women and 17,000 controls.

"Genome-wide association study identifies novel breast cancer susceptibility loci."
Douglas F. Easton, Karen A. Pooley, Alison M. Dunning, et al.
Nature advance online publication 27 May 2007
doi:10.1038/nature05887

Click here for Abstract.

"A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer."
David J Hunter, Peter Kraft, Kevin B Jacobs, et al.
Nature Genetics advance online publication 27 May 2007
doi:10.1038/ng2075

Click here for Abstract.

"Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer."
Simon N Stacey, Andrei Manolescu, Patrick Sulem, et al.
Nature Genetics advance online publication 27 May 2007
doi:10.1038/ng2064

Click here for Abstract.

Written by: Catharine Paddock
Writer: Medical News Today
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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