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BCRF Grantee Since

2005

Donor Recognition

The Tanger Outlets Award

Kenneth Offit, MD, MPH

Chief, Clinical Genetics Service
Vice Chairman, Academic Affairs, Department of Medicine
Co-Head, Program in Cancer Prevention, Control and Population Research
Department of Clinical Genetics Service
Memorial Sloan Kettering Cancer Center
Member, Cancer Biology and Genetics Program, Sloan Kettering Institute
Professor of Medicine and Public Health, Weill Cornell Medical College
New York, New York

Current Research

Two decades after the initial identification of BRCA1 and BRCA2 there remains considerable uncertainty regarding cancer risks associated with inherited mutations of these genes. Dr.Offit’s BCRF research is part of an international effort to identify genetic "protective factors" that modify risk of breast cancer in BRCA2 mutation carriers. He is currently working on two BCRF-funded studies. In one study, Dr. Offit and his colleagues are assembling and analyzing samples from 10,000 BRCA2 mutation carriers as part of the "Oncochip" that is being used to test greater than 600,000 cancer samples this year. They have also assembled a team that has begun developing a clinical research protocol to bring this testing for "genomic modifiers" to the clinic. In the coming year, Dr. Offit and his colleagues will continue their efforts in identifying new BRCA risk modifiers by looking at RNA expression in addition to DNA mutations. Ultimately, these methods will inform the preventive choices of women with inherited BRCA2 mutations.

Dr. Offit’s second BCRF project is conducted jointly with Dr. Mark Robson and brings together several studies using next generation sequencing (NGS) of DNA to define causes of inherited breast and ovarian cancer. While BRCA1 and BRCA 2 are the two most commonly mutated genes in breast and ovarian cancer, they can only explain a small portion of these cancers that occur at high frequencies in families. Drs. Offit and Robson have joined with BCRF colleagues  Katherine Nathanson and Fergus Couch to sequence the exomes (coding regions within a gene) and whole genomes of women with BRCA negative breast and ovarian cancer. Via weekly conference calls and data exchange with BCRF colleagues, they have forged a working consortium and have recently received a grant from the National Cancer Institute to further this effort. In the coming year they will continue analysis of "spontaneous" changes (those not present in parents) in inherited DNA associated with cancer in young patients with breast cancer compared to parental DNA. As part of this study, they have initiated a protocol that allows them to provide the results of full genome analyses, i.e. all of a patient’s known inherited risk to all diseases, to selected individuals.  These studies are advancing our understanding of hereditary breast and ovarian cancer and have generated several published papers in the scientific literature bearing on the operational, medical, as well as ethical challenges of "personalized" genomic counseling.

Bio

Kenneth Offit is Chief of the Clinical Genetics Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSKCC). He is also Professor of Medicine and Public Health at Weill Medical College of Cornell University, and Vice Chairman of the Program in Prevention, Control and Population Research at MSKCC. He received his AB at Princeton University and his MD and MPH from the Harvard Medical School and the Harvard School of Public Health. He is a member of the American Society for Clinical Investigation. He was awarded an American Cancer Society Career Research Recognition Award and the 2013 ASCO American Cancer Society Award for research in cancer prevention. Dr Offit is a member of the Board of Scientific Counselors of the National Cancer Institute, and of the Evaluation of Genomic Applications in Practice and Prevention working group of the U.S. Centers for Disease Control.

Dr. Offit's research team identified the most common mutation associated with hereditary breast and ovarian cancer in those of Ashkenazi Jewish ancestry. His group also published the first prospective study documenting a decreased risk of breast and ovarian cancer following oophorectomy in women carrying inherited mutations of the BRCA genes, and the first genome wide association study of BRCA2 mutation carriers. Dr Offit's group has discovered or characterized inherited mutations associated with risk of breast, ovarian, colon cancer, non-Hodgkin's lymphoma, and other malignancies. His laboratory currently focuses on utilizing genomic approaches to discover novel mechanisms associated with increased risk for common malignancies, or which modify the risks of known hereditary predispositions.