Study Supports Universal Germline Genetic Testing Regardless of Age at Cancer Diagnosis

By The ASCO Post Staff Posted: 10/15/2026 9:00:00 AM Last Updated: 10/14/2026 12:42:41 PM Universal germline genetic testing after an individual receives a cancer diagnosis may help to uncover hereditary cancer risks in the patient's family, according to findings published in Cancer Discovery .

In a study of a pan–solid tumor cohort, researchers found enriched germline pathogenic variants in individuals with subtype-specific early-onset cancer. The researchers suggested that most of these patients would have been missed by standard age cutoffs, and that the findings support universal germline genetic testing for all individuals who are diagnosed with cancer.

“Hereditary cancer can occur at any age, and we should move toward a new standard in which genetic testing is considered for every patient diagnosed with cancer, regardless of age,” said co-corresponding author Luis A. Diaz, Jr., MD, FAACR , Head of Solid Tumor Oncology at Memorial Sloan Kettering (MSK) Cancer Center.

“Our manuscript shows that relying on age at diagnosis misses a substantial proportion of patients with germline pathogenic variants and provides strong support for moving toward universal germline genetic testing in patients with cancer.” Background and Study Methods Standard germline testing of individuals with cancer excludes patients over the age of 50 years, as it was previously assumed that patients with average- or late-onset cancers are less likely to have hereditary cancers than those with early-onset cancer.

The researchers conducted germline genetic sequencing with the MSK-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay on 39,184 unselected patients with 32 solid tumor malignancies. They specifically looked at 94 cancer predisposition genes. Patients were also stratified into groups based on the timing of onset.

“The current standard practice is, in many ways, a gatekeeper for genetic testing. Our study aimed to assess how much inherited cancer risk we miss when we rely too heavily on age at diagnosis,” said co-corresponding author Zsofia K. Stadler, MD , Chief of the Clinical Genetics Service and Associate Director, Robert and Kate Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center.

“As opposed to using an arbitrary cutoff such as age 50, we hypothesized that universal germline genetic testing would give us valuable insight into all patients regardless of age and potentially facilitate more testing for patients’ family members who may also carry hereditary cancer risk.” Key Findings A total of 16.3% of the sequenced patients had at least one germline pathogenic variant in a cancer predisposition gene.

The prevalence of pathogenic variants was inversely correlated with age at diagnosis, including 18.4% of patients with early-onset tumors, 15.6% in those with average-onset tumors, and 12.3% in patients with late-onset tumors ( P < .001). Enrichment in early-onset tumors was mostly contributed to variants in high-/moderate-penetrance genes, accounting for 12.4% of early-onset cases, 8.9% of average-onset cases, and 5.1% of late-onset cases ( P < .001).

The researchers calculated that if they had restricted hereditary cancer testing to patients under the age of 50, in line with standard practice, they would have missed 4,601 pathogenic variant carriers, accounting for 72% of all variants identified. Universal germline genetic testing would also allow for more cascade testing, according to the study authors.

“Unfortunately, cascade testing remains one of the most underused opportunities in cancer prevention," Dr. Stadler commented. "Once a hereditary cancer predisposition variant is identified in one patient, testing relatives becomes highly targeted and informative, yet only a minority of eligible relatives currently undergo testing.” The study authors noted that the study was limited to a single major tertiary cancer center and that certain cancers were over- or underrepresented, especially as the cohort predominantly included patients of European and Ashkenazi Jewish ancestry.

DISCLOSURES: The study was funded by grants from the National Institutes of Health and Memorial Sloan Kettering Cancer Center. Dr. Stadler disclosed intellectual property rights in SOPHiA Genetics and serves as editor-in-chief for JCO Precision Oncology and as a section editor for UpToDate.

Dr. Diaz serves as an editor-in-chief of Cancer Discovery ; in keeping with AACR editorial policy, a member of the Cancer Discovery editorial board managed the consideration process for this submission and independently rendered the final decision concerning acceptability. Dr.

Diaz disclosed membership on the board of directors of Quest Diagnostics and Epitope, and he acts as a consultant to Function Health, Grove Biopharma, Inc., Innovatus Capital Partners, Inc., Seer, Absci, DELFI Diagnostics, Inc., and NeoPhore. Dr. Diaz is listed as an inventor on several licensed patents regarding circulating tumor DNA analysis and mismatch repair deficiency technologies for diagnosis and therapy.

Some of these roles may involve equity or royalty payments to inventors. The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.