Multigene panel testing (MGPT) is a tool to identify genetic mutations that can increase an individual’s risk of a disease such as cancer. MGPT can also be used to develop a treatment plan or to help predict whether cancer will spread to other parts of the body. A recent study examined colorectal cancer (CRC) patients and found that 14.2% of patients carried at least one pathogenic germline variant (PGV), with more than one PGV identified in 1.4% of patients. 

Identification of pathogenic or likely PGVs in hereditary cancer predisposition genes can affect a patient’s treatment plan. While there is increased support for universal MGPT for certain forms of cancer, eligibility criteria for CRC are more restrictive: germline genetic testing for CRC is recommended only for a subset of patients with CRC who meet certain “high-risk criteria,” which include:

  • Diagnosis before 50 years 
  • Lynch syndrome–related cancers 
  • Having a family history of certain Lynch syndrome-related cancers 
  • Abnormalities in mismatch repair immunohistochemistry

The above mentioned study conducted MGPT across a diverse CRC population to determine whether genetic testing criteria for patients with CRC should be broadened. The results of the study found that of the 34,244 individuals who were tested:

  • 14.2% of individuals carried at least one PGV, with more than one PGV identified in 1.4% 
  • 11.9% of individuals carried a clinically actionable variant, including 9.1% carrying a PGV in a gene associated with an increased CRC/polyposis risk 
  • 5.7% of individuals carried Lynch syndrome–related PGVs 

This research study is the largest to date examining MGPT in CRC, and demonstrated high rates of clinically actionable variants detected, independent of the age at the time of testing, the number of genes on the panel, and race/ethnicity. These findings provide evidence to support the broadening of genetic testing criteria for patients with CRC, which in turn will have a significant impact on disease management, the treatment plan, and ultimately, disease outcome.

 

Genetic factors play an important role in the development of colorectal cancer (CRC). Some people have inherited genetic syndromes that increase their risk for colon cancer. Genetic testing looks for these inherited syndromes along with changes in DNA that are associated with a greater likelihood of developing cancer. 

What is Genetic Testing for CRC?

Genetic testing looks for changes in your DNA that are known to be associated with an increased risk of cancer. Generally, there are two ways that genetic testing may be used: 

  • Before a person develops cancer to determine their level of risk
  • Following a cancer diagnosis to see if genetic changes may have contributed to the cancer

According to the American Cancer Society, genetic tests can help show if members of certain families have inherited a high risk of CRC due to inherited cancer syndromes such as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC) or familial adenomatous polyposis (FAP).

Who is Considered “High-Risk”?

Those with a family history of CRC may benefit from speaking to their primary care physician, oncologist, or surgeon about the importance of genetic testing to identify if there was a mutated gene that predisposes them to cancer. You may be a good candidate for genetic testing for CRC if you have:

  • Close family members, such as parents, children, or siblings, who have been diagnosed with CRC
  • Many people on one side of your family who’ve been diagnosed with CRC
  • A personal or family history of CRC diagnosis at a young age
  • A personal or family history of an inherited genetic syndrome that increases CRC risk
  • A personal or family history of multiple cancers
  • A strong family history of CRC or other cancers that are associated with an inherited genetic syndrome
  • More than 10 adenomatous polyps found during CRC screening

What Can I Expect With the Procedure?

If your doctor believes that you’re a good candidate for genetic testing, they’ll likely refer you to a genetic counselor. Genetic testing is typically done using a blood sample. However, it may also use a sample of saliva, cheek cells, or skin. This sample will be sent to a specialized lab that will run the test. After a few weeks, your results will be sent over to your doctor or genetic counselor and you’ll be contacted to discuss your test results and next steps.

How Much Does Genetic Testing for Colon Cancer Cost and is it Covered by Insurance?

Genetic testing can be expensive and can cost between $100 to over $2,000, depending on the nature and complexity of the test. Many insurance providers will cover the cost of genetic testing and genetic counseling if it’s considered medically necessary. 

  • Most private health insurers cover genetic counseling and testing with low- or no out-of-pocket costs for people who meet certain personal or family cancer history criteria.
  • Medicare covers genetic testing for people with a cancer diagnosis who meet certain criteria; you must have a cancer diagnosis to qualify for coverage of genetic testing for an inherited mutation.
  • Medicaid programs cover BRCA genetic counseling and testing for qualifying individuals, including those with a known mutation in the family, or specific personal and/or family history of cancer for all but two states: Alabama and Rhode Island.

Nevertheless, always check with your insurance provider to see what’s covered before getting tested. For additional information about insurance coverage, please visit: Paying for Genetic Services.

 

Kitty Chiu is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

Clinical decision support systems (CDSS) are computer-based applications used to analyze data within electronic health records (EHRs). CDS algorithms are progressively being integrated into healthcare systems to expand patient care. However, research and development in ethical frameworks have uncovered that CDS applications can perpetuate bias in healthcare. A recent EHR quality improvement study has revealed significant differences in family history accessibility, availability, and comprehensiveness based on sex, race and ethnicity, and language preference. These findings propose that historically medically underserved populations are excluded from identification from CDS tools based on family history information, unintentionally reinforcing existing healthcare disparities and potentially creating more disparities in healthcare systems.

 

decision support system

Colorectal cancer (CRC) is the third most diagnosed cancer and over 5 million people worldwide currently live with CRC. According to the American Cancer Society, the lifetime risk of developing CRC is 1 in 23 for men and 1 in 25 for women, and recent research indicates an increased incidence of CRC among individuals younger than 50 years of age.

Recent research has revealed that a significant number of CRC patients with heritable genetic mutations remain undiagnosed under past genetic testing guidelines, which limited testing to specific age groups and forms of cancer. Now, the National Comprehensive Cancer Network (NCCN) has announced new guidelines that recommend germline multigene panel testing for all individuals with CRC ages <50, as well as consideration for germline multigene panel testing for those with evidence of mismatch repair deficiency in their tumor or a family history of CRC. 

Robert Nussbaum, M.D., co-authored a letter to the NCCN to formally request universal germline testing for CRC patients to be added to the guidelines. He states, “As the medical community’s understanding of genetic links to cancer evolves, genetic testing guidelines must evolve with it.” Increased accessibility to multipanel genetic testing can extend the representation of medically underserved populations and reduce the exacerbation of existing disparities. Expanding guidelines for genetic testing for CRC can also help family members determine their risk for CRC, increase surveillance for early detection, discover curative treatments, and promote awareness of CRC for those at increased risk. 

Universal Versus Guideline-Directed Targeted Testing for Hereditary Cancer 

Genetic factors play a significant role in the risk of developing many forms of cancer. Identification of germline predisposition can notably determine and direct a more effective plan of care, treatment, risk-reducing interventions, cancer screening, and germline testing. A multicenter cohort study among 2,984 cancer patients compared universal genetic testing with guideline-directed targeted genetic testing based on clinical guidelines to examine the prevalence of pathogenic germline variants (PGVs) in cancer patients. One in eight patients had a pathogenic germline variant, but 48% of those cases would not have been identified with a guideline-based approach. This underscores the limitations of clinical and guideline-based risk assessment for genetic testing. The multigene panel was more efficient at identifying heritable variants compared to guideline-directed targeted genetic testing. 

Importantly, identifying PGVs in cancer patients can encourage their relatives to take earlier action for risk assessment and cancer prevention. However, financial barriers and lack of insurance coverage can limit patient participation in genetic screening. This study points to the effectiveness of multigene panel testing and its implications for cancer prevention and treatment.

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.