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Kenneth Offit, MD, MPH
Co-Head, Program in Cancer Prevention, Control and Population Research
Memorial Sloan Kettering Cancer Center
Professor of Medicine and Public Health,
Weill Cornell Medical College
New York, New York
- Seeking to understand the causes of hereditary breast and ovarian cancer.
- Genetic studies are ongoing to characterize the drivers of hereditary breast cancers and to identify new drug targets to prevent this disease in high-risk families.
- These studies will lead to more precise risk assessment and personalized prevention and treatment strategies.
The breast cancer susceptibility genes BRCA1 and BRCA2 are the most well-known genes implicated in inherited breast and ovarian cancer susceptibility. Since the discovery of the BRCA cancer causing mutations, much work has been done to identify other cancer-causing gene mutations. Drs. Offit and Robson are conducting multiple studies aimed at understanding the influence of BRCA and other genes in inherited breast and ovarian cancer. Their work has led to breakthroughs in our understanding and awareness of genetic risks of breast and ovarian cancer.
Full Research Summary
Dr. Offit's BCRF project is conducted jointly with Dr. Mark Robson and brings together several studies using next-generation sequencing of DNA to define causes of inherited breast and ovarian cancer.
Although BRCA1 and BRCA2 are the two most commonly mutated genes in breast and ovarian cancer, they explain only a small portion of familial breast cancers. Drs. Offit and Robson have joined with BCRF colleagues Drs. Katherine Nathanson and Fergus Couch to sequence the exomes (coding regions within genes) and whole genomes of women with BRCA-negative breast and ovarian cancer.
They have identified a novel genetic syndrome of breast cancer susceptibility associated with a gene in the "nucleotide excision repair pathway" in those of Ashkenazi (Eastern European Jewish) background. This year, the team will conduct laboratory studies to determine whether these cancers may be especially sensitive to a drug that targets this genetic defect.
The team is also expanding on previous work in which they use a collection of DNA samples from tens of thousands of tumors and normal biospecimens to discover new susceptibility genes in breast, ovarian, and other cancers.
In addition, the group will continue to work with BCRF colleagues to put into place an internet-assisted testing program for Ashkenazi “founder” BRCA mutations called the “BRCA Founder OutReach (BFOR) Study,”.
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.
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.