Five Percent of U.S. Population Carries Pathogenic Variants Associated with Cancer Risk

Historically, genetic research focused on identifying significant variants in cancer susceptibility genes in people with cancer or with known risk factors such as a hereditary disposition to cancer. New research by Cleveland Clinic found that upwards of 5% of Americans have some genetic susceptibility to cancer, regardless of lifestyle or family history. The study results were published in JAMA.

Background

Led by Joshua Arbesman, M.D., and Ying Ni, Ph.D., the research team discovered that the genetic risk for cancer is more common than previously thought.

“Instead of studying individuals who already have cancer, we were thinking about how cancer develops and how we can implement better screening and surveillance,” says Dr. Ni. “We needed a huge, unbiased cohort to evaluate that question.”

The research team calculated the statistics through an analysis of health records and genetic sequencing data from the NIH All of Us Research Program. As the largest known U.S. data set, All of Us includes various racial and ethnic groups that best represent the current U.S. population .

Previously, genetic research primarily involved people of European ancestry. This limited researchers’ abilities to characterize genetic changes in people of other backgrounds.

Study findings

Of the roughly 400,000 people in the database, an estimated 20,000 people are carriers of pathogenic variants in at least one of 70 common cancer-related genes. “We realized genetic mutations were likely more common in the general population than originally expected,” says Dr. Arbesman. “These data substantiate the fact that we shouldn’t be as strict in terms of who is referred for genetic testing.”

Dr. Ni notes that their team made very conservative estimations, stating, “We believe the true prevalence is higher, but we were very stringent in our analysis.”

As part of the analysis, the researchers studied more than 3,400 variants. “By looking at every single gene, we may gain a better understanding of genes that have not been as well understood to date,” says Dr. Ni.

The study authors note that further research is needed to validate their findings. In addition, many questions remain, such as how much each genetic alteration may increase the overall cancer risk and which cancers people should be screened for and when. “Some of these genes increase the risk of cancer a lot and some only impact it minimally, so follow-up data is needed to tease out those details,” explains Dr. Arbesman.

What’s next

The researchers are now conducting detailed follow-up studies to better understand clues about the highest genetic risks. The hope is that studies like this will ultimately help clinicians make informed decisions about prioritizing specific screening tests.

In the meantime, the researchers hope that the study findings will reinforce the value of age-appropriate cancer screening in the general population. As genetic testing becomes easier and less expensive, it’s likely more patients will take advantage of these assessments.