PHILADELPHIA - Many women with a faulty breast cancer gene could be at greater risk of the disease due to extra risk-amplifying genes, according to research published this month in the American Journal of Human Genetics.
Researchers at the University of Pennsylvania School of Medicine join an international consortium of research groups that looked at more than 10,000 women carrying a BRCA1 or BRCA2 mutation for breast-cancer risk.
“These results suggest that knowledge of a BRCA1 or BRCA2 mutation is necessary, but not sufficient, to fully understand cancer risk in women who carry these mutations,” says co-author and head of the North American coalition Timothy R. Rebbeck, PhD, Professor of Epidemiology at Penn. “This paper demonstrated that other genes, and possibly exposures, could provide important information that may refine our ability to predict cancer in this high-risk population. Because carriers of BRCA1 or BRCA2 mutations are relatively rare in the population, the only way to undertake studies of this type is by forming large consortia.” Rebbeck is also the Associate Director for Population Science at Penn’s Abramson Cancer Center
“This is the first time we have found evidence that common changes in other genes can amplify the risk of breast cancer in women known to have faulty BRCA genes,” says lead author Professor Doug Easton, director of Cancer Research UK’s Genetic Epidemiology Unit at the University of Cambridge. “This is the first step in finding a set of genes that modify the risk in BRCA carriers, and may influence how we monitor women with a family history of the disease.”
The international team of scientists have found that common versions of two genes – FGFR2 and TNRC9 – known to increase breast cancer risk in the general population – also increase the risk in women carrying damaged versions of the BRCA2 gene.
Around one in eighteen women will develop breast cancer by the age of 65. On average, half of women carrying a faulty BRCA2 gene will develop the disease by the age of 70.
This study found that particular combinations of the FGFR2 and TNRC9 genes modify breast cancer risk in BRCA2 mutation carriers. One percent of BRCA2 mutation carriers have the highest risk combination of FGFR2 and TNRC9 genes. Seven in every 10 women in this category are predicted to develop breast cancer.
Around twenty percent of the BRCA2 mutation carriers have the lowest risk combination of the FGFR2 and TNRC9 genes. The researchers found that their risk is lowered so four in every 10 women in this category are expected to develop the disease.
These findings are the first step in a series of studies hunting for breast cancer susceptibility genes, which aims to better monitor and treat women with a family history of the disease.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals — its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center — a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, comprised of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 300 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.