Multi-Gene Testing in Colorectal Cancer Patients Could Detect More Hereditary Cancer Syndromes

The implementation of multi-gene panel testing may be a necessary part of the standard of care for all colorectal cancer patients.

The implementation of multi-gene panel testing may be a necessary part of the standard of care for all colorectal cancer patients, according to new data from the Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC—James).

In the study, the investigators found that 38.6% of people with colon cancer who have a hereditary cancer syndrome, which includes 6.3% of those with Lynch syndrome, may have undetectable conditions by means of the current universal tumor-screening methods. This is significant since at least 7.1% of people with colorectal cancer also have an identifiable inherited genetic mutation, which the current screening methods may not be able to detect.

From a cohort of more than 3300 colorectal cancer patients who were treated at 51 hospitals in Ohio, the investigators observed that a potential solution to this problem may be in the implementation of multi-gene panel testing.

“Finding ways to identify high-risk individuals among colorectal cancer patients is critically needed to better manage this disease and proactively identify family members who may also be impacted,” said first author of the study Rachel Pearlman, MS, LGC, a genetic counselor/researcher at the OSUCCC—James, in a press release. “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.”

During the study, the investigators assessed whether the use of a multi-level genetic testing would identify known hereditary genetic risk factors that can be passed down within families. However, patients usually do not become aware of their genetics-based risk for cancer until that cancer is already detected. The ability to identify the potential for hereditary cancer syndrome among colorectal cancer patients’ family members could help to detect risk before a cancer diagnosis in these populations.

In the study, patients who had undergone surgery for invasive colorectal cancer between January 2013 and December 2016 were included, with all participants receiving a universal tumor screening for mismatch repair (MMR) deficiency. This characteristic in particular was tested because it is common in tumors in patients with Lynch syndrome and suggests that the tumor may have a positive response to immunotherapy as well, according to the researchers.

Lynch syndrome is helpful to identify in patients because it is a cancer-causing condition that occurs if a person inherits a mutation in 1 of 4 genes. If someone in the family of a patient with colorectal cancer has Lynch syndrome, then they are at a greater risk of developing colorectal, uterine, ovarian, and stomach cancer.

Among participants who met at least 1 of the trial-inclusion criteria, the multi-gene panel testing they received helped to identify harmful mutations. The criteria for this testing included MMR deficiency, colorectal cancer diagnosis before age 50, multiple primary tumors, or a first-degree relative with colorectal or endometrial cancer.

Upon analyzing the data, the investigators found that approximately 16% of participants had MMR deficiency and approximately 7% had an inherited mutation. The investigators noted that the results also demonstrated that if universal tumor screening for Lynch syndrome was the only method to screen for hereditary cancer syndromes, Lynch syndrome would have gone undetected in more than 38% of the patients who tested positive for it.

“This is a significant and important discovery. By using pan-cancer multi-gene panel testing for all colorectal cancer patients, we could identify many individuals who are at increased risk for future cancer development and identify actionable therapeutic targets for their current cancer,” said study senior author Heather Hampel, MS, LGC, a member of the OSUCCC—James Molecular Carcinogenesis and Chemoprevention Program and a professor and associate director of the Division of Human Genetics at the Ohio State College of Medicine, in a press release. “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.”


Multi-Gene Testing Could Detect More Hereditary Cancer Syndromes. Columbus, OH: Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute; May 6, 2021. [email] Accessed May 10, 2021.