The first wave of routine genetics testing has already helped millions of people learn about their hereditary risk for certain diseases such as cancer. But a new study published this week in JAMA suggests that as our knowledge of genetics expands, these initial results sometimes need to be revised.
Researchers at the University of Texas Southwestern Medical Center decided to look at the results of over 1.5 million genetic tests given to 1.45 million people from a single nearby laboratory since 2006. The tests were meant to pinpoint a person’s genetic risk of cancer, with the majority of patients being women.
From 2006 to 2018, they found, there were nearly 60,000 amended reports that needed to be issued because an unique genetic variant identified in the initial result had been reclassified as either likely harmless or potentially risky after the test was taken. Overall, around 6.4 per cent of the 45,000 unique variants found in these tests (taken from 2006 to 2016) had been reclassified.
Most of these revisions didn’t come from genetic variants that had been identified as benign or risky. Only 0.2 per cent of risky or likely risky genes had been downgraded, for instance. The bulk of revisions came from genetic variations that we simply didn’t know the significance of. About 25 per cent of unknown variants identified in these tests (184,327 in total) were reclassified.
“If a variant is reclassified to being pathogenic, then it matters to the patient,” said senior author Theo Ross, a cancer geneticist and professor of internal medicine at the university, in a statement.
People who have newly identified mutations for Lynch syndrome, a genetic condition that raises the likelihood of several cancers, including colon, skin and brain cancer, need more regular screening tests like colonoscopies and at an earlier age, Ross offered as an example. And even in the case of newly identified benign mutations, the amended results can provide a peace of mind.
Overall, over 90 per cent of unknown mutations in the study were reclassified as benign, while just under eight per cent were reclassified as risky or likely risky. But despite that mostly good news, the team’s findings also highlight just how quickly new research can change our understanding of genetic risk. In the study, they noted, it took a median length of less than two years for amended reports to be sent back out to patients.
“The implications of this study are three-pronged,” she said. “Physicians need to be aware of how rapidly knowledge about gene variants is advancing and that reclassifications are common. Labs need to review gene variant information on a regular basis and alert physicians to changes. Finally, patients and their family members need to be made aware of reclassifications by their physicians so they can make well-informed choices.”