Kenneth Offit, MD, MPH
Vice Chairman, Academic Affairs, Department of Medicine
Vice Chairman, Program in Cancer Prevention Control and Population Research
Department of Clinical Genetics Service
Memorial Sloan-Kettering Cancer Center
Member, Cancer Biology and Genetics Program (joint), Sloan-Kettering Institute
Professor of Medicine and Public Health, Weill Cornell Medical College
New York, New York
2013-2014 BCRF Projects:
1) The Sandra Taub Memorial Award
Co-Investigator: Mark E. Robson, MD, Memorial Sloan-Kettering Cancer Center, New York
A decade and a half after the initial identification of BRCA1 and BRCA2, there remains considerable uncertainty regarding cancer risks associated with inherited mutations of these genes. The basis of this variation of risk is most striking for BRCA2 and affects clinical management: patients with the same BRCA2 mutation will develop breast, ovarian, or other cancers at different ages or not at all. In this international study, we used a genomic scan to find genetic “protective factors.” We published our discovery of one marker, near the gene ZNF365 on chromosome 10, which decreases risk of breast cancer about 25% in BRCA2 mutation carriers. In this past year, Drs. Offit and Robson published in PLoS Genetics their analysis of ~10,000 BRCA2 carriers worldwide and identified the first genetic marker found to modify risk of breast cancer only in BRCA2 mutation carriers. This marker on chromosome 6 near the gene TFAP2A was associated with a 15% reduction in breast cancer risk in BRCA2 mutation carriers. Drs. Offit, Robson, and others also completed preliminary analysis using the “exome chip” and contributed a list of candidates to the “Oncochip” that will be used to test >600,000 cancer samples next year. Looking forward, they have recruited a behavioral scientist and have already begun work on a clinical research protocol to bring this testing for “genomic modifiers” to the clinic to inform the decisions of women at hereditary risk for breast cancer by virtue of an inherited BRCA2 mutation.
2) Dr. Offit is conducting a second project entitled “Genomic Susceptibility to Breast and Ovarian Cancer,” which brings together several studies using “next generation sequencing” (NGS) to define causes of inherited breast and ovarian cancer. In 2013-2014, his team will continue their ascertainment of parent child trios to identify de novo rare mutations associated with early onset breast cancer. The major focus of this grant period will be pursue the collaboration established with co-BCRF grantees Drs. Katherine Nathanson (University of Pennsylvania) and Fergus Couch (Mayo Clinic) in order to combine their variant data on BRCA negative breast cancer kindreds (joint) breast ovarian cancer probands (MSKCC) and early onset breast cancer cases (MSKCC-Broad). These investigators are also committed to translating genomic information to patients, both to guide breast cancer prevention as well as to inform other aspects of their health care (based in the “incidentalome”) as part of "personalized preventive medicine."
Kenneth Offit, MD, MPH, is Chief of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center, a Member of the Program in Cancer Biology and Genetics at the Sloan-Kettering Institute, and a Professor of Medicine and Public Health at the Weill College of Medicine of Cornell University. He is a graduate of Princeton University, the Harvard School of Public Health, and the Harvard Medical School. In 1996, his research group discovered the most common genetic mutation associated with inherited breast and ovarian cancer, occurring among Jews of European ancestry. Dr. Offit’s lab also discovered or described recurrent mutations causing increased risk for colon and prostate cancer. In 2002, his group was the first to prospectively measure the impact of preventive ovarian surgery in individuals carrying BRCA mutations. In 2010, his group performed the first genome wide association study of BRCA2 breast cancer and he is currently using next generation sequencing to define genomic markers of risk for leukemia, lymphoma, breast, ovarian and prostate cancers.
Dr. Offit received the 2013 American Cancer Society-American Society of Clinical Oncology Award for his research in cancer prevention, and his text, Clinical Cancer Genetics: Risk Management and Counseling, won an award in Medical Sciences from the Association of American Publishers. He is currently a member of the Board of Scientific Counselors of the U.S. National Cancer Institute, and the Evaluation of Genomic Applications in Practice and Prevention working group of the U.S. Centers for Disease Control.