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Breast cancer risk gene discovery fast tracked by new technology
Date:3/29/2012

An international team of researchers led by the University of Melbourne has used new technology to fast track the discovery of a breast cancer risk gene and could assist in the discovery of other cancer genes.

Professor Melissa Southey of the Genetic Epidemiology Laboratory, Department of Pathology at the University of Melbourne, who led the study, said it was a significant discovery and the first breast cancer risk gene to be discovered using the latest genetic sequencing technology.

"The mutations in the newly identified gene XRCC2, although rare, explain another proportion of breast cancers that run in families where there is no known genetic cause and that particularly occur at an early age," she said.

"We identified this gene quite quickly using genetic technology called massively parallel sequencing, which enables sequencing of large amounts of human DNA at high speed.'

"Due to these results and our methodology we believe that further risk genes will be identified at a faster rate than before and potentially for other cancers such as colorectal and prostate cancers," she said.

Professor Southey said the discovery could help manage the risk of breast cancer for families with a strong history of the disease and no known genetic cause.

"This discovery will assist some families to determine individual risk and which family members are at high risk of contracting the disease," Professor Southey said.

"Unaffected relatives of people with a mutation in this gene could also be offered predictive testing, subsequent genetic counselling and ongoing clinical management on the basis of their mutation status.'

"People whose breast cancer is associated with XRCC2 mutations could also benefit from specific treatments that target the genetic fault," she said.

Currently, only about 30 per cent of the familial risk for breast cancer has been explained, leaving the substantial majority still unaccounted for.

"Research indicates that no single gene is likely to account for a large proportion of the remaining unexplained genetic susceptibility to breast cancer," Professor Southey said.

"Although mutations in XRCC2 are rare, it is most likely that the remaining unknown breast cancer susceptibility genes will account for similar small proportions of the disease."

Initially, using massively parallel sequencing, researchers identified XRCC2 mutations in two families (in Melbourne and the Netherlands). This was followed by a larger series of studies using DNA from blood samples of 689 families with multiple members affected by breast cancer, and from 1308 women who were affected at an early age by breast cancer and recruited from the general population, as well as 1120 controls.

More XRCC2 mutations were detected in the breast cancer cases but not in the controls. These additional studies were conducted in Melbourne and at the International Agency for Research on Cancer (IARC) in France.

Co-first author Dr Daniel Park of the University's Department of Pathology (with Dr Fabienne Lesueur of IARC) said the study demonstrated the power of massively parallel sequencing for discovering susceptibility genes for common, complex diseases like breast cancer.

"Our study approach could be applied to many other common, complex diseases with components of unexplained heritability, such as colorectal and prostate cancers," he said.

Professor Southey oversaw this work with two long-standing collaborators and experts in the field of breast cancer genetics, Associate Professor Sean Tavtigian and Professor David Goldgar at the University of Utah.


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Contact: Rebecca Scott
rebeccas@unimelb.edu.au
61-383-440-181
University of Melbourne
Source:Eurekalert

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