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Study Explores Rates of Germline Mutations in Patients With Colorectal Cancer


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In a recent study published by Uson Junior et al in Clinical Gastroenterology and Hepatology, researchers found one in six patients with colorectal cancer had an inherited cancer-related genetic mutation, which may be linked to a predisposition to the disease. In addition, the researchers discovered that 60% of these cases would not have been detected if relying on a standard guideline-based approach.

Study Details and Findings

"We found that 15.5% of 361 patients with colorectal cancer had an inherited mutation in a gene associated with the development of their cancer," said senior study author N. Jewel Samadder, MD, a gastroenterologist and hepatologist at the Mayo Clinic. "We also found that over 1 in 10 of these patients had modifications in their medical or surgical therapy based on the genetic findings."

N. Jewel Samadder, MD

N. Jewel Samadder, MD

After a median follow-up of 20.7 months, no differences in overall survival were seen between those with or without a pathogenic germline variant (P = .2). 

The patients were tested with a sequencing panel that included more than 80 cancer-causing or predisposing genes; in comparison, standard panels for colorectal cancer only include 20 or fewer genes. The patients with colorectal cancer were part of a larger cohort of 3,000 patients involved in the 2-year Interrogating Cancer Etiology Using Proactive Genetic Testing (INTERCEPT) study and were newly diagnosed with various cancers at Mayo Clinic Cancer Center locations in Arizona, Florida, and Minnesota. 

Cancer Management in Families

The study findings emphasize that uncovering hidden inherited genetic mutations using a universal testing approach and broader gene panels could lead to opportunities for cancer management in families and targeted cancer therapies that can save lives.

Although many mutations that cause colorectal cancer happen by chance in a single cell—including from environmental factors, diet, smoking, and alcohol use—the study confirms many are inherited mutations that set off a cycle of events that can lead to cancer.

"Though the most common mutations were found in genes typically associated with colorectal cancer, we found that a substantial number of mutations were present in genes typically associated with breast and ovarian cancer," Dr. Samadder explained. "This may lead to novel targeted therapies based on the cancer's unique genetic basis.”

Equally important to the discovery of a patient's inherited cancer mutation is the potential for patients to share the heritable cause of their disease with their blood relatives, allowing family members to pursue care for earlier disease detection and cancer management. 

"The power of genetics is that we can foresee the cancer that will develop in other family members," said Dr. Samadder. "This can allow us to target cancer screening to those high-risk individuals and hopefully prevent cancer altogether in the next generation of the family."

In the study, all blood-related family members of patients found to have a genetic mutation were offered free genetic testing—overall, just 16% of these family members underwent testing, which may suggest there are nonfinancial barriers to genetic testing. 

Disclosure: Support for this project was provided by the Mayo Transform the Practice Grant, Mayo Clinic Center for Individualized Medicine, Desert Mountain Members’ CARE Foundation, and David and Twila Woods Foundation. For full disclosures of the study authors, visit cghjournal.org.

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®.
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