American Cancer Society Professor
Departments of Medicine and Genome Sciences
University of Washington
Dr. King is working with several BCRF colleagues on two studies that are focused on understanding the genetic susceptibility of breast cancer. The New York Breast Cancer Study (NYBCS) is a study to identify all genes responsible for inherited predisposition to breast cancer among women of Ashkenazi Jewish ancestry and, by extension, among women of all ancestries. Dr. King and Ms. Marks use genomic sequencing to evaluate DNA from women who have developed breast cancer and from their relatives to identify inherited mutations in genes critical to the development of breast cancer. The goal of the NYBCS for the coming year is to identify mutations responsible for breast cancer in families of any ancestry with no inherited mutations in any of the known breast cancer genes. The study investigators believe that much of the remaining genetic risk of breast cancer, both in the NYBCS and among women generally, is due to mutations that lie in regions of the genome where they may alter expression of breast cancer genes, but cannot be detected by existing approaches. Therefore, Dr. King and Ms. Marks will integrate whole genome sequencing with bioinformatics tools and experimental biology to characterize other gene mutations associated with inherited breast cancer in high-risk families of any ancestry, as well as early-onset patients of Ashkenazi Jewish ancestry from the NYBCS. The goal is to search for cancer-predisposing mutations wherever they exist in the genome.
A sister project of the New York Breast Cancer Study (NYBCS) is the Middle East Breast Cancer Study (MEBCS). MEBCS is directed jointly by Ephrat Levy-Lahad, MD, of Shaare Zedek Hospital and Hebrew University, Jerusalem, Israel; Moien Kanaan, PhD, of Bethlehem University, Bethlehem, Palestinian Authority, and Dr. King. As of this year, the MEBCS has enrolled 1000 breast cancer patients of Palestinian and Arab-Israeli origins and has completed genomic analysis comprising BRCA1 and BRCA2 and more than 30 other known and candidate breast cancer genes for 400 of these patients. In more than 10 percent of the young-onset and familial patients, they have identified the inherited mutation responsible for their disease. These mutations appeared not only in BRCA1 and BRCA2 but in a total of 11 different breast cancer genes.The observation supports the hypothesis that breast cancer has many different genetic causes and therefore that studying this population will enable discovery of new genes underlying breast cancer in women from all parts of the world.
In parallel, the researchers are establishing a comprehensive infrastructure for breast and ovarian cancer genetics services on the West Bank with clinical, laboratory, and bioinformatics capacities. They are providing genetic counseling and testing for breast and ovarian cancer patients at Augusta Victoria Hospital in East Jerusalem and at El Hussein Hospital in Beit Jala, a major breast cancer referral center on the West Bank. Laboratory and bioinformatics capacities at Bethlehem University are growing with development of genomic sequencing capacity.
Mary-Claire King, PhD, is American Cancer Society Professor at the University of Washington, Seattle. She was the first to show that breast cancer is inherited in some families, as the result of mutations in the gene that she named BRCA1. In addition to inherited breast and ovarian cancer, her research interests include the genetic bases of schizophrenia, genetic disorders in children, and human evolution. She pioneered the use of DNA sequencing for human rights investigations. Dr. King has been elected to the National Academy of Sciences, the American Academy of Arts and Sciences, the Institute of Medicine, the American Philosophical Society, and as a foreign member of the French Academy of Sciences. She has served on the Advisory Committee to the Director of NIH; the National Commission on Breast Cancer of the President’s Cancer Panel, multiple councils and study sections of the NIH, and as past president of the American Society of Human Genetics.