10/22/2025
Patients without risk factors could benefit from genetic testing for cancer, study suggests
New evidence from Cleveland Clinic suggests far more Americans may need genetic testing for cancer than current guidelines recognize. The research, published in JAMA, found that up to 5% of Americans (almost 17 million people) carry genetic mutations, or “variants,” associated with increased cancer susceptibility – regardless of risk factors like personal or family cancer history.
The research team, led by Joshua Arbesman, MD, and Ying Ni, PhD, analyzed health records and genetic sequencing data from almost half a million Americans who participated in the National Institute of Health's All of Us Research Program, the country’s largest and most comprehensive genetic and healthcare database.
“Genetic testing has traditionally been reserved for individuals with strong family histories or other high-risk indicators,” says Dr. Arbesman, a practicing dermatologist and researcher. “Our findings show that many people with pathogenic variants don’t meet those criteria, suggesting we may be missing opportunities for early detection and prevention.”
The study focused on over 70 of the most common genes whose mutations predispose individuals to cancer (colloquially called “cancer genes”) and identified over 3,400 unique variants. The most variants were found in famous cancer-associated genes in the list, but all of the genes they tested had detectable variants in the population.
“Knowing the prevalence of gene variants in the general population will give us an unbiased picture without any pre-assumptions based on lifestyle or family history,” says Dr. Ni.
This study builds on earlier work by Drs. Arbesman and Ni, who found that genetic predisposition to melanoma was 7.5 times higher than national guidelines estimated. Those findings highlighted to Dr. Arbesman just how underrecognized genetic risk can be in routine clinical settings.
As genetic testing becomes easier and cheaper, Drs. Arbesman and Ni hope that their growing evidence of how widespread cancer risk variants are will support broader access to testing.
Dr. Arbesman says that it’s possible their findings could still underreport the rates of mutations that increase cancer risk in the general population, because the medical field still doesn’t know every gene that increases cancer risk when mutated. Another Cleveland Clinic researcher, even identified a bone cancer predisposition gene less than a week before Drs. Ni and Arbesman’s paper was published.
“In the short term, our work can inform clinical practice,” Dr. Arbesman says. “Long term, we hope to build a truly comprehensive list of genes that guide cancer screening and prevention, so we can find people who really need preventative care before it’s too late.”
