Fergus J. Couch, PhD

2009-2010 BCRF Project:

On behalf of Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
Evidence suggests that 35% of women with BRCA1 mutations will never develop breast cancer but it is currently not possible to predict which BRCA1 mutation carriers are in this category. Dr. Couch and his collaborators propose to validate the results from a genome wide association study of BRCA1 carriers in order to identify the commonly inherited alterations in the human genome that are associated with altered risk of breast cancer in BRCA1 mutation carriers. Once a number of these risk modifiers have been verified, they aim to develop new risk assessment models for BRCA1 carriers that will predict individual risk of breast cancer.

To date, the genome wide analysis of genetic alterations has been completed and the 96 alterations most significantly associated with breast cancer risk have been identified. These are being further tested in another 7,500 BRCA1 mutation carriers to identify the alterations that truly influence breast cancer risk.

Mid-Year Progress Report:
The first stage of the analysis using DNA samples from 2,400 BRCA1 mutation carriers has been completed and the 88 variants showing the most significant associations with breast cancer risk have been further evaluated. Of these, five variants from a single chromosomal region have shown convincing associations with breast cancer. Thus, the genome wide association study has successfully identified markers that account, in part, for the tremendous variability in the age of onset of breast cancer in BRCA1 mutation carriers. These markers and others that will be identified through additional follow-up studies, will be used to develop better methods for predicting risk of breast cancer in individuals carrying BRCA1 mutations.

Bio:
Fergus J. Couch is an Associate Professor in the Department of Laboratory Medicine and Pathology in the Mayo Clinic College of Medicine. He obtained his undergraduate and Ph.D degrees from University College Cork, Ireland and received postdoctoral training under the mentorship of Francis S. Collins at the University of Michigan and Barbara L. Weber at the University of Pennsylvania. He is the vice-chair of the Division of Experimental Pathology and the deputy director of the breast cancer research program at the Mayo Clinic.

Dr. Couch has had a long-standing interest in the genetics of breast cancer following his involvement in the initial characterization of the BRCA1 and BRCA2 genes as a postdoctoral fellow. Dr. Couch is taking a multidisciplinary approach to characterization of genetic factors associated with breast cancer. Much of his work is focused on identification of common genetic risk factors for breast cancer and genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. In addition, he leads an international consortium that is using laboratory and epidemiological approaches to determine which unclassified variants in BRCA1 and BRCA2 predispose to cancer. Dr. Couch is also studying how BRCA2 and a number of candidate oncogenes from a region of gene amplification on chromosome 17 contribute to breast cancer using animal models and cell biology approaches. His studies of these genes have led to a specific interest in the contribution of defects in cell division to breast cancer.