RESEARCH TRIANGLE PARK – A few generations ago, the first clear signal that you had high cholesterol was often a heart attack — or worse, sudden death.

The medical landscape has changed dramatically since then – doctors now routinely screen adults for elevated cholesterol levels – and it continues to evolve at a rapid pace. The next generation, our children or grandchildren, will likely be genetically tested for familial hypercholesterolemia (hereditary high cholesterol) if there’s a family history of elevated low-density lipoprotein. LDL is the “bad” cholesterol linked to heart attacks.

Early detection provides an opportunity to make healthier lifestyle choices now, before any real damage is done. Coupled with cholesterol-lowering medications, it could reduce the need for surgery later and lessen the likelihood of early death.

That’s the promise of population screening. It can use genetic information to identify seemingly healthy people who harbor a high risk of a hereditary disease, well before they become ill. Early intervention is important because the sooner people discover they’re prone to a health problem, the easier it can be to manage. And the better the outcome.

Population screening isn’t new. The first guidelines were developed more than 50 years ago by European scientists James Maxwell Glover Wilson and Gunner Jungner. Wilson was principal medical officer at the Ministry of Health in London, and Jungner was chief of the Department of Clinical Chemistry at Sahlgren’s Hospital in Gothenburg, Sweden.

Since then, large-scale prenatal and infant screenings have become the norm for conditions that include Down syndrome and phenylketonuria, more commonly known as PKU. Left untreated, this disorder can result in mental and intellectual disability and seizures. Adults are routinely screened for colon cancer. And women undergo periodic mammographies for breast cancer.

Population screening may directly help 6.5 million in U.S.

Recent advances in genomics, coupled with lower costs, have kicked population screening into a higher gear. And that has opened the door to tremendous opportunity. An estimated 1 to 2 percent of the U.S. population has a genetic makeup that puts it at a much higher risk for serious, yet preventable disease. That’s an estimated 6.5 million people who might directly gain from screening programs.

The North Carolina Biotechnology Center is exploring the potential benefits and pitfalls of population screening, and supporting research to determine its clinical value to the state.

Sara Imhof

“Testing for hereditary diseases can have tremendous public health benefit in terms of early intervention for high-risk people,” says Sara Imhof, Ph.D., NCBiotech’s senior director for precision health. “It also can work hand-in-glove with our efforts in precision health to consider genetic, lifestyle, and environmental factors in developing more personalized ways to treat and prevent illness.”

Imhof is one of more than two dozen experts — members of the Genetics and Population Health Action Collaborative (GPHAC) — who recently published a discussion paper on population screening. It examines the best ways to advance the concept. And it outlines the challenges of setting up genomics-based screening programs.

The group is an advisory arm of the National Academies of Sciences, Engineering, and Medicine. James Evans, M.D., Ph.D., from the University of North Carolina at Chapel Hill, co-chaired the effort to which Misha Angrist, Ph.D., from nearby Duke University, also contributed.

In addition, NCBiotech has partnered with Color, a leading consumer-focused genomics company, to pilot a population screening program in the state. That initiative, to begin in the spring of 2019, will be disclosed soon.

Advantages and disadvantages of population screening

As noted above, population screening can make a big difference to people’s health. Individuals who are at a high risk for certain diseases can begin their medical follow-up and personalized prevention plans sooner, rather than later. Early intervention can slow or stop the progression of disease, or help prevent its development. Treatment costs also are likely to be lower.

But population screening isn’t a slam dunk. It introduces considerable challenges. Finding a disorder early is helpful only if an effective treatment exists that can provide a better health outcome. And even though individuals may be at higher risk for a disease, they won’t always get sick. In those cases, screening and monitoring may lead to interventions that waste time, money and other resources, and can cause unnecessary physical or emotional distress.

Science is a constantly evolving, imperfect art. No screening test – genetic or otherwise – is perfect in today’s world. X-rays cause radiation exposure, for example. Endoscopies, colonoscopies, and other invasive procedures can occasionally cause serious injury. False positive test results can lead to unnecessary examinations and needless worry. False negatives can mean that some high-risk patients who need help don’t get it.

There also is a question of cost. While genetic tests may be far less expensive than they were a decade ago, education is still important for all screening participants. Genetic counseling is a must for anyone with an elevated risk of any kind.

Then there are the families of participants who test positive for a particular condition. Those family members – or at least some of them – should be screened. That’s an additional expense. What will insurance cover?

How results are used, and their confidentiality, likewise come into play. Will individuals be denied medical insurance if they have a predisposition for a certain disease?

Underlying issues don’t dampen the excitement

These and other underlying issues aren’t likely to quell the growing interest in population screening as a valuable public health tool. Still, with recent advances in technology, researchers are discovering new disease genes faster than they can evaluate them.

As a result, GPHAC has recommended a conservative approach until we know more about the utility of genetic testing.

The organization’s roadmap focuses on 10 genes with well-understood links to three conditions that can be prevented or treated effectively. These include:

  • Lynch syndrome, also known as hereditary non-polyposis colorectal cancer;
  • Hereditary breast and ovarian cancer; and
  • Familial hypercholesterolemia.

GPHAC relies on three criteria to identify its targets:

  • A high likelihood of a disorder that can cause serious illness or death;
  • Well-established treatments for those who are at risk; and
  • A solid base of knowledge about the gene and related health conditions.

The group believes its approach will likely be most effective at saving lives and preventing disease, with the least amount of potential harm to the general population.

“How we might use this…technology to benefit the general population is one of the most exciting tasks now confronting the field of genomics,” the GPHAC discussion paper concluded. “The potential gains inherent in worthwhile public health interventions are enormous… .”

Imhof believes the same is true in North Carolina. “While we still have much to learn, population screening has a bright future,” she says. “We want our state to lead this effort so we can take full advantage of all it has to offer.”

(C) N.C. Biotech Center

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