Mayo Clinic Researchers Discover Novel Approach to Estimate Risk of Breast Cancer
Rochester, MN (PRWEB) May 1, 2008 -- In a paper published today, a team of medical researchers from the Mayo Clinic (www.mayoclinic.com) in collaboration with academic colleagues from the University of Utah, France, and Australia report on the outcome of a study that analyzes the risk for breast cancer imparted by inherited mutations in the BRCA2 gene.
Mutations in the BRCA2 gene have been strongly linked to familial breast cancer. Inheritance of one mutation in BRCA2 can lead to up to more than 90% lifetime risk of acquiring breast cancer. The BRCA2 gene has a critical role inside the cell in repairing damaged DNA. Unfortunately, it has been difficult to determine which mutations in BRCA2 cause breast cancer and which don't since individual mutations are relatively rare and are only found running in a handful of families in the world. Hence it is impossible to estimate risk of breast cancer by epidemiological methods. The lead author of the present study, Daniel J. Farrugia, M.D., Ph.D. of the Mayo Clinic in Rochester, Minn., explained that an epidemiological study published last year of more than 1400 mutations only managed to identify 43 mutations that could be reliably linked to breast cancer.
In a novel approach, the authors of the study experimentally introduced these mutations in BRCA2 into cells, and evaluated which mutations disrupted the function of BRCA2 inside the cell. In particular, they tested whether the mutation had any effect on the ability of the cell to repair DNA. Failure to repair DNA leads the way for the cell to accumulate additional mutations in other genes, ultimately leading to development of breast cancer. The authors also measured the effect of the mutations in BRCA2 on the number of centrosomes, structures within the cell that are vital for ensuring error-free cell division. These structures are frequently found in increased numbers within the cell in tumor cells.
The authors found that their two assays correlated very well with each other and could reliably distinguish inherited mutations that disrupted BRCA2 and thus cause breast cancer from those that did not. To validate their novel approach, the authors then compared their results with those from the epidemiological study published last year and found a very strong correlation. Fergus J. Couch, Ph.D., the leader of the research team, said that since this study proved that this novel approach works in principle, his team has now expanded this study to approximately a hundred other mutations of unknown clinical significance that will be evaluated in an identical fashion for breast cancer risk.
Knowing which mutations disrupt BRCA2 function and start the cell on its path to cancer will enable better clinical decision making and enable doctors to maintain closer supervision to patients and family members that inherit these mutations. On the other hand, patients that harbor mutations that can be reliably shown not to affect the function of BRCA2 may be reassured that they are not at increased risk for cancer, and thus avoid needless screening and potentially harmful surgery.
The paper, entitled "Functional assays for classification of BRCA2 variants of uncertain significance (http://cancerres.aacrjournals.org/cgi/content/abstract/68/9/3523)," is published today in both the online edition and print version of the bimonthly research journal Cancer Research.
Contact:
Fergus J. Couch, Ph.D., Mayo Clinic College of Medicine, Rochester, MN
Phone: (507) 284-3623,
Daniel J. Farrugia, M.D., Ph.D., Mayo Clinic College of Medicine, Rochester, MN
Phone: (507) 266-0878
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