Genomic screening to detect preventable rare diseases in healthy people

March 07, 2013
Millions of people unknowingly carry rare gene mutations that place them at high risk of developing preventable diseases such as colorectal and breast cancers and several catastrophic blood vessel disorders.Researchers from the University of North Carolina at Chapel Hill’s Gillings School of Global Public Health and School of Medicine propose that screening healthy adults for these and other specific, rare genetic disorders potentially could prevent these diseases. Their commentary in the March 7 issue of Genetics in Medicine offers a framework for how such screening might be developed.
Dr. Andrew Olshan

Dr. Andrew Olshan

“Our commentary provides an exciting new way of thinking about relatively rare conditions that collectively may have broader public health implications,” said co-author Andrew Olshan, PhD. “The revolution in DNA sequencing methods has put into reach new public health approaches previously unavailable. It’s a very exciting prospect for public health genomics.”

Olshan is professor and chair of epidemiology at the Gillings School of Global Public Health and associate director for population sciences and leader of the UNC Lineberger Comprehensive Cancer Center’s Cancer Epidemiology Program.

The authors assert that rapid progress in affordable, robust DNA sequencing offers a promising opportunity to identify preventable rare diseases such as Lynch Syndrome, an inherited cancer of the digestive tract. “For example,” they state, “just the roughly 0.2 percent of individuals in the U.S. (over 600,000 people) who harbor deleterious mutations in any one of four Lynch-associated genes are at greater than 80 percent risk for preventable colon cancer.”

When other similar genetic conditions are considered, millions of individuals in the U.S. are at risk for preventable diseases – if those risks are identified. At a current cost of approximately $200 per sample, such genomic screening may be warranted, given the high costs of these disorders (in both suffering and dollars) once they occur.

“With this commentary,” said first author James Evans, MD, PhD, “we’re issuing a call to the genomic and public health communities to investigate the feasibility of identifying individuals in the population who are, unbeknownst to them, at high risk of preventable disease. Such an effort could benefit millions of individuals in the U.S. alone.”

Evans is the Bryson Distinguished Professor of Genetics and Medicine in the UNC School of Medicine and leader of the Clinical Cancer Genetics Program at UNC Lineberger Comprehensive Cancer Center.

The commentary cites challenges that must be addressed if this partnership is to succeed, including selection of those mutated genes that confer the highest disease risk in the population and for which there are effective and acceptable preventive strategies. Another issue is minimizing false positives.

The “worry factor” is a phenomenon that occurs with other screenings, including ones for cholesterol, blood pressure and cervical dysplasia. “While discovery doesn’t equal diagnosis, patients who learn that they carry mutations may worry that getting the disease is inevitable. We will need to develop counseling resources to help patients understand their risk,” Evans said.

The authors point out that, in the case of newborn screening, a defined process determines which disease screens should be included, based on available evidence and stakeholders’ perceptions. A similar process would be established for adult screening.

Co-authors are Barbara K. Rimer, DrPH, dean and Alumni Distinguished Professor at Gillings School of Global Public Health; and Jonathan Berg, MD, PhD, assistant professor of clinical genetics, and Terry Magnuson, PhD, professor and chair of genetics and vice dean for research, both at the UNC School of Medicine.

Work on the paper was funded by the National Human Genome Research Institute Clinical Sequencing Laboratory Research Consortium. The NHGRI is one of the National Institutes of Health.


Gillings School of Global Public Health contact: David Pesci, director of communications, (919) 962-2600 or