Standard Multigene Testing Could Detect More Hereditary Cancer Syndromes in Patients With Colorectal Cancer

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Up to 38.6% of people with colon cancer who have a hereditary cancer syndrome—including 6.3% of those with Lynch syndrome—could have their conditions remain undetected with current universal tumor-screening methods, and at least 7.1% of people with colorectal cancer have an identifiable inherited genetic mutation, according to new data published by Pearlman et al in JCO Precision Oncology.

The authors said their data, which was gathered from a cohort of more than 3,300 patients with colorectal cancer treated at 51 hospitals across Ohio, makes a strong scientific argument for implementing multigene panel testing as part of the standard of care for all patients with colorectal cancer.

“Finding ways to identify high-risk individuals among patients with colorectal cancer is critically needed to better manage this disease and proactively identify family members who may also be impacted,” said Rachel Pearlman, MS, LGC, first author of the study and a genetic counselor/researcher at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James). “Genetic screening has changed dramatically in the past 10 years, allowing us to screen individuals for numerous known genetic mutations for much lower costs. This is a powerful tool that we need to embrace more broadly for cancer prevention and surveillance."

Study Methods and Results

For this study, researchers wanted to know if using a multilevel genetic testing approach could better identify hereditary genetic risk factors that increase a person’s lifetime risk of cancer, but often go undetected until cancer occurs.

Researchers identified 3,310 adults who had undergone surgery for invasive colorectal cancer from January 2013 to December 2016. Individuals were recruited as part of the Pelotonia-funded Ohio Colorectal Cancer Prevention Initiative (OCCPI), a statewide research initiative led by Heather Hampel, MS, LGC, a member of the OSUCCC–James Molecular Carcinogenesis and Chemoprevention Program as well as Professor and Associate Director of the Division of Human Genetics at the Ohio State College of Medicine.

By using pan-cancer multigene panel testing for all patients with colorectal cancer, we could identify many individuals who are at increased risk for future cancer development and identify actionable therapeutic targets for their current cancer.
— Heather Hampel, MS, LGC

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The study was launched to screen newly diagnosed patients with colorectal cancer and their biologic relatives for Lynch syndrome, a cancer-causing condition that occurs if a person inherits a mutation in one of four genes. People with Lynch syndrome are at higher risk of developing colorectal, endometrial, ovarian, and stomach cancers than average-risk individuals.

All study participants received universal tumor screening for mismatch repair (MMR) deficiency. This characteristic is common in tumors from patients with Lynch syndrome and suggests that the tumor would respond well to immunotherapy.

Individuals who met at least one of the trial-inclusion criteria also received multigene panel testing to identify harmful mutations. Genetic testing criteria included MMR deficiency; colorectal cancer diagnosis before age 50; multiple primary tumors (colorectal cancer/endometrial cancer); or a first-degree relative with colorectal or endometrial cancer.

Researchers report in this new analysis that about 16% of participants (n = 525) had MMR deficiency and about 7% had an inherited mutation. The scientists noted that if universal tumor screening for Lynch syndrome had been the only method used to screen for hereditary cancer syndromes, more than 38% of patients who tested positive would have been missed—including more than 6% of individuals found to have Lynch syndrome through multigene testing methods.

“This is a significant and important discovery. By using pan-cancer multigene panel testing for all patients with colorectal cancer, we could identify many individuals who are at increased risk for future cancer development and identify actionable therapeutic targets for their current cancer,” said Ms. Hampel, senior author of the study. “Adopting modern testing methods as part of standard clinical practice for patients with colorectal cancer could literally save thousands of lives through early detection and surveillance of other family members who are at increased risk to develop the cancer based on inherited genetic mutations.”

Disclosure: For full disclosures of the study authors, visit

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®.