Mary-Claire King, PhD

1) The New York Breast Cancer Study
Co-Investigator: Joan H. Marks, MS, New York Breast Cancer Study at Sarah Lawrence College, Bronxville, NY

TThe goals of the New York Breast Cancer Study are to identify genes underlying inherited risk of breast cancer among women of Ashkenazi Jewish ancestry, then to generalize their findings from Jewish women to women of all ancestries. This year, for the first time, the researchers have the capacity to address this question by sequencing the entire genomes of selected breast cancer patients. Their subjects for complete genome sequencing are five Ashkenazi Jewish women who developed breast cancer and whose families have been severely affected, but who have normal sequence of all known breast cancer genes. Inherited mutations predisposing to breast cancer in these patients could occur in anywhere in the human genome. By determining their complete genome sequences, the investigators will identify every rare genetic variant and evaluate which are coinherited with breast cancer in their families and which are associated with breast cancer in the Ashkenazi population as a whole. New breast cancer genes identified in the Ashkenazi Jewish populations will then be sequenced for other mutations in other populations.

2) Co-Investigators: Ephrat Levy-Lahad, MD, Shaare Zedek Medical Center, Jerusalem, Israel; and Moein Kanaan, PhD, Bethlehem University, Palestinian Authority

Drs. King, Levy-Lahad and Kanaan have created an infrastructure for Cancer Genetics counseling and testing for Arab women in the Palestinian Authority and Israel. Following a training course developed by the investigators and hosted at Shaare Zedek Medical Center (SZMC) in Jerusalem, Palestinian genetic counselors now provide counseling at Augusta Victoria Hospital in East Jerusalem, the major referral hospital for Palestinian cancer patients, ArabCare Hospital in Ramallah and Bethlehem University (BU). Laboratory infrastructure for sequencing and full BRCA1 and BRCA2 analysis has been established at the Hereditary Research Lab in Bethlehem University.

In the Palestinian Authority and Israel combined, they have enrolled over 250 Arab women with breast cancer. More than 20% of these women have family history suggestive of an inherited predisposition to breast cancer, and genetic analysis of BRCA1 and BRCA2 mutations is now underway at both BU and SZMC. In women with personal and family history of breast or ovarian cancer, full analysis of BRCA1 and BRCA2 is performed. Other study participants are tested for mutations previously found in Arab families.

Current results suggest that when specific BRCA1 and BRCA2 mutations occur within families, they are not recurrent or common in the general Arab population. Continued analyses will allow the researchers to identify the spectrum of mutations characteristic of the Arab population. They are planning to extend the study by searching for novel breast cancer genes using novel genomic technologies. Breast cancer genetic services established for the Palestinian population will ultimately increase their understanding of the causes of breast cancer in general and is already enabling early detection and prevention in this population.

Bio:
Mary-Claire King is American Cancer Society Research Professor of Genetics and Medicine at the University of Washington. Work in her lab focuses on genetic analysis of breast and ovarian cancer. Dr. King was the first to prove that breast cancer is inherited in some families. She is now studying BRCA1 and BRCA2 and searching for other breast and ovarian cancer genes. Her other medical research interests include genetic analysis of inherited deafness and systemic lupus erythematosus. Her lab is also interested in human genetic diversity and evolution, and in the application of DNA sequencing to human rights problems.

Dr. King received her BA in Mathematics from Carleton College, her PhD in Genetics from University of California at Berkeley, and her postdoctoral training at UC San Francisco. She has served on the National Commission on Breast Cancer of the President's Cancer Panel, the advisory board of the NIH Office of Research on Women's Health, the Council of the NIH Fogarty Center, the advisory board of the National Action Plan for Breast Cancer, the NIH Breast Cancer Program Review Group, the Board of Scientific Counselors of NCI, the Board of Scientific Counselors of Memorial Sloan-Kettering Cancer Center, the National Research Council committee to advise the Department of Defense on their Breast Cancer Research Program, and many NIH study sections. Abroad, she has served as Consultant to the Commission on the Disappearance of Persons of the Republic of Argentina and has carried out DNA identifications for the United Nations War Crimes Tribunal.

Dr. King has been elected to Phi Beta Kappa and Sigma Xi, as a Fellow of the AAAS, to the Institute of Medicine (and its Council), to the American Academy of Arts and Sciences,and as honorary chair for Washington state for the 50th Anniversary of the United Nations. She has received the Clowes Award for Basic Research from the American Association for Cancer Research, the Jill Rose Award from The Breast Cancer Research Foundation, the Brinker Award from the Komen Foundation, a Woman of the Year Award from Glamour magazine, and honorary doctorates from Carleton, Smith, Bard, and Dartmouth Colleges. She has one daughter, Emily, who lives and works in Berkeley.