Common Genetic Variation Impacts Breast Cancer Diagnosis in Older Women

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Researchers from The Cancer Institute of New Jersey (CINJ) are converging on Washington, D.C., this week for the 101st Annual Meeting of the American Association for Cancer Research (AACR) to share their findings on how a common genetic variation can impact diagnosis of breast cancer in postmenopausal women. They are joining other top investigators from around the globe for the event, which is highlighting interdisciplinary approaches to cancer research. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

At focus is the tumor-suppressor gene known as TSC1 and the role it plays in tumor growth in breast cancer. Mutation in either TSC1 or a companion gene known as TSC2, a relatively rare occurrence, is known to cause non-cancerous growths in multiple vital organs – a genetic condition known as tuberous sclerosis. Less clear is a possible association between more common variations in these genes known as polymorphisms, and the formation of breast cancer. These variations are the subject of the CINJ research.

Investigators, led by Kim M. Hirshfield, MD, PhD, medical oncologist at CINJ and assistant professor of medicine at UMDNJ-Robert Wood Johnson Medical School, selected TSC1 because it plays a role in the cell growth pathway regulated by a protein known as mTOR.

The mTOR pathway is being used for targeted treatment of several types of cancers including breast cancer. The Hirshfield laboratory previously reported on polymorphisms in p53 tumor suppressor pathway genes that associate age with diagnosis of breast cancer and on how these associations depend on the genetic and environmental characteristics of breast cancer.

In this latest research, blood samples from more than 1,000 women recruited through CINJ clinics were evaluated for the presence of genetic changes in the DNA sequence of the TSC1 gene. The team’s findings show that the presence of a specific DNA change does not affect age of diagnosis of breast cancer for young patients, but does appear to delay disease onset in postmenopausal women. They note the presence of this genetic change likely makes TSC1 more sensitive to the effects of low amounts of estrogens found in women who are postmenopausal and confers a protective benefit by reducing the amount of cell growth.

“This research will provide the groundwork for understanding how common genetic changes in TSC1 may affect risk of developing breast and other cancers but may also provide clues for identifying those patients who may receive the most benefit from therapies targeting the mTOR pathway,” noted Dr. Hirshfield.

The author team also includes Madhura S. Mehta, BS, UMDNJ-Robert Wood Johnson Medical School; and Alexei Vazquez, PhD, CINJ, UMDNJ-Robert Wood Johnson Medical School. The work is supported by funding from The Breast Cancer Research Foundation, Ruth Estrin Goldberg Memorial for Cancer Research, and The New Jersey Commission on Cancer Research.

The work represented by CINJ members is among the 6,300 abstracts being presented at the gathering, which is featuring more than 17,000 researchers, healthcare professionals, and patient advocates. The event is open to registered participants.

About The Cancer Institute of New Jersey
The Cancer Institute of New Jersey (http://www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center dedicated to improving the detection, treatment and care of patients with cancer, and serving as an education resource for cancer prevention. CINJ’s physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. To make a tax-deductible gift to support CINJ, call 732-235-8614 or visit http://www.cinjfoundation.org. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

The CINJ Network is comprised of hospitals throughout the state and provides a mechanism to rapidly disseminate important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon Cancer Center at Overlook Hospital, Cooper University Hospital and Jersey Shore University Medical Center. Affiliate Hospitals: Bayshore Community Hospital, CentraState Healthcare System, JFK Medical Center, Mountainside Hospital, Raritan Bay Medical Center, Robert Wood Johnson University Hospital at Hamilton (CINJ at Hamilton), Saint Peter’s University Hospital, Somerset Medical Center, Southern Ocean County Hospital, The University Hospital/UMDNJ-New Jersey Medical School, and University Medical Center at Princeton.

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Source:  Cancer Institute of New Jersey

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