Fergus J. Couch, PhD
Professor and Chair
2012-2013 BCRF Project:
On behalf of Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
Division of Experimental Pathology
Department of Laboratory Medicine and Pathology
Dr. Couch's team has completed the first two phases of a large genome-wide association study aimed at the identification of inherited genetic variants that modify the risk for breast cancer in BRCA1 mutation carriers. They found that seven different regions of the human genome contain modifiers of breast cancer risk in BRCA1 mutation carriers and two regions contained separate modifiers of ovarian cancer risk. These markers will be used to develop better methods for predicting risk of breast and ovarian cancer in individuals carrying BRCA1 mutations.
In the next year, Dr. Couch's team will continue the study with the intent of identifying modifiers of breast cancer risk that can be used for improved risk assessment for this population. They will evaluate all genetic variation in regions that influence breast cancer risk in BRCA1 mutation carriers and will attempt to identify new, previously overlooked, rare inherited genetic alterations that influence breast cancer risk in BRCA1 mutation carriers. The study is expected to lead to a better understanding of how BRCA1 breast tumors develop and to improve estimation of individual risk of breast cancer.
Mid-year Progress: This study involves identification of commonly inherited genetic variants that modify the risk for breast cancer in BRCA1 mutation carriers. It involves the evaluation of 32,000 selected genetic variants in DNA samples from 15,272 BRCA1 mutation carriers. Dr. Couch's team has identified new breast cancer risk factors on chromosomes 1q32 (MDM2), 5p (TERT), 6q25 (ESR1), 10q25 (TCF7L2), 12p24 (PTHLH), and 19p13.1 (MERIT40). These new risk factors are also linked to aggressive estrogen receptor negative and triple negative breast cancers in the general population. Separately, the investigators have identified two new ovarian cancer risk factors for BRCA1 mutation carriers on chromosomes 4q32 and 17q21. The 4q32 risk factor is only associated with ovarian cancer in BRCA1 carriers. These risk factors have also been used to generate risk models that can identify BRCA1 carriers with breast cancer risk as low as 28% and as high as 99% and ovarian cancer risk as low as 28% and as high as 63%. These risk models can now be used in clinics to predict individual risk of breast and ovarian cancer for BRCA1 mutation carriers. Further analyses to identify more risk factors for BRCA1 mutations carriers are underway.
Fergus J. Couch is Professor and Chair of the Division of Experimental Pathology in the Department of Laboratory Medicine and Pathology. He obtained his undergraduate and doctoral 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.