A study from California, USA, analyzed 34,244 patients with a history of colorectal cancer who underwent germline multigene panel testing between March 2015 and May 2021. Overall, 14.2% of all eligible patients were found to have at least one clinically meaningful gene variant, 9.1% were found to have a gene variant associated with an increased risk of colorectal cancer or polyps, and 3.1% were reported to have a gene variant associated with other cancers. Across all ages, races, and panel sizes tested, more than 7.9% had clinically meaningful genetic variants. 38.2% were categorized as having genetic variants but with unknown clinical significance, suggesting they should be followed up. Of the total 34,244 patients, 35.5% had been diagnosed with a cancer other than colorectal cancer, and patients with multiple cancers were more likely to have a genetically significant pathogenic variant compared to patients diagnosed with colorectal cancer alone (14.1% vs 13.0%).

Having a genetically significant variant can mean a lot, not only to you, but also to your family. Patients who carry a mutation associated with hereditary cancer should be tested to see if their family members also carry the mutation, and cancer prevention strategies should include aggressive screening for cancer risk, even in families where cancer has not yet been detected.

When we analyzed the hereditary cancer panels that patients had, we found that the size of the genetic testing panel did not make a difference in detecting important variants, but larger panels were more likely to detect variants whose clinical significance is not yet clear.

Although it is recommended that hereditary cancer panel testing be performed in patients with colorectal cancer when the age of diagnosis is less than 50 years and a first-degree relative has been diagnosed with colorectal cancer before the age of 50, or when two or more first-degree relatives have been diagnosed with colorectal cancer, regardless of age, even if the patient does not meet these criteria, it is likely that the patient carries a gene associated with hereditary cancer.

However, even with hereditary cancer panel testing, immunohistochemical staining or PCR testing for MSI status should be performed independently as it is important in determining who is eligible for immunotherapy.