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

The goals of the New York Breast Cancer Study are to identify genes underlying inherited risk of breast cancer among women of Ashkenazi Jewish ancestry, to characterize factors that modify these risks, and to generalize our findings from Jewish women to women of all ancestries. In previous years, the NYBCS has characterized the risks of breast and ovarian cancer due to inherited mutations in BRCA1 and BRCA2, and identified non-genetic factors that modify those risks. They now seek to identify genes responsible for inherited breast cancer in high-risk Ashkenazi Jewish families with no mutations in BRCA1 or BRCA2.

In the past year, evidence from the NYBCS suggests that inherited breast cancer risk among women without mutations in BRCA1 or BRCA2 can be due to mutations in any of several genes, with one or two individually rare mutations playing a role in each severely affected family. This perspective differs from the mainstream view that remaining breast cancer risk is due to the combined influence of multiple small-effect variants. Finding the critically important genes will have a major impact on identification of women at high risk of breast cancer and on the interventions offered to these women.

Mid-Year Progress Report:
The goals of the New York Breast Cancer Study are to identify genes underlying inherited risk of breast cancer among women of Ashkenazi Jewish (AJ) ancestry, then to generalize these findings from AJ women to women of all ancestries. In previous years, the NYBCS has characterized the risks of breast and ovarian cancer due to BRCA1 and BRCA2, identified non-genetic factors that modify those risks, and discovered previously unknown mutations that increase breast cancer risk. The researchers now seek to identify genes responsible for inherited breast cancer in women with no mutations in BRCA1 or BRCA2.

To answer this question, they are undertaking this year a new genomics initiative: The 1000 Exons Project. This initiative combines genealogical analysis of breast cancer in families, network analysis of biological interactions between BRCA1 and BRCA2 and their protein partners, array-based identification of extended chromosomal regions shared by multiple mothers and daughters with breast cancer, and high-throughput parallel sequencing of the coding sequences (exons) of genes. This is the first time such an effort has been undertaken to identify genes for any illness. These technologies are very young and their integration is novel.

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

The goal of this project is to provide genetic analysis of BRCA1 and BRCA2 and cancer genetic counseling services for inherited breast cancer predisposition among Palestinian and Arab-Israeli women in the Middle East. In the Middle East, genetic analysis and medical follow-up services for breast and ovarian cancer risk are among the best in the world for Jewish women. However, neither genetic analysis nor follow-up services have yet been extended to women of other ancestries in the region.

The researchers propose to address this challenge. Leading oncologists in Israel and Palestine and a superb Palestinian-Israeli breast cancer advocacy group are their partners in this effort. Palestinian and Israeli geneticists, oncologists, and advocacy leaders know each other well. Thus women with inherited breast cancer, and women at risk thereof, can be referred appropriately in both Palestine and Israel. The missing piece of the puzzle is to identify these women by genetic testing within the context of genetic counseling.

Click here to read more about the study

Mid-Year Progress Report:
The purpose of this project is to understand the genetic basis of inherited predisposition to breast cancer among Arab women in the Middle East. The project is sponsored by BCRF at Bethlehem University (BU) in the Palestinian Authority and Share Zedek Medical Center (SZMC) in Israel. Breast cancer has historically appeared less frequently among Arab women in the Middle East than among women in the West. However, breast cancer incidence is now increasing in the Arab population, and Arab women are generally diagnosed at younger ages, with more aggressive disease, and a higher proportion of patients have a family history of breast or ovarian cancer. This suggests that genetic factors may play a substantial role in causing breast cancer in the Arab population. It is now possible to test for many of these factors, including mutations in the known breast cancer genes BRCA1 and BRCA2, but this requires appropriate clinical awareness, knowledge of genetics, infrastructure for genetics counseling and testing, and provision for medical follow-up services.

In the first months of the project, the researchers' aim was to establish this necessary framework. To this end, Bethlehem University established a collaborative agreement with Augusta Victoria Hospital (AVH) in East Jerusalem, the major referral hospital for Palestinian cancer patients. The agreement includes creation of a Cancer Genetics Counseling Service for breast cancer patients treated at AVH and assures patients and their families of appropriate care and follow-up. A training course for Arab genetic counselors was developed by the study investigators, and six Palestinian women received entry permits to attend the course at SZMC in Israel. The classroom part of the course was completed in January, and in-service training of the genetic counselors is underway at AVH and Shaare Zedek Medical Center. The researchers now will be able to provide cancer genetic services to Palestinian women, and begin genetic analysis of breast cancer in this population. Ultimately ,this will increase our understanding of the causes of breast cancer and enable 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.