Genetic tests for colon cancer serve two distinct purposes. They analyze a person’s DNA for specific changes (mutations or variants) that either predispose them to cancer or affect how an established tumor responds to treatment. These alterations can significantly increase the lifetime risk of developing colon cancer or provide a roadmap for personalized therapy after a diagnosis. Understanding the difference between these two approaches is necessary for evaluating personal risk or treatment options.
Testing for Inherited Colon Cancer Risk
Germline testing identifies inherited mutations passed down through a family that significantly increase the risk of developing colon cancer. The test uses non-cancerous cells, often from blood or saliva, to detect genetic changes present in nearly every cell of the body.
Candidates typically have a strong family history of colon cancer, such as multiple close relatives diagnosed, or a diagnosis before age 50. Individuals with a personal history of multiple Lynch syndrome-associated cancers, like endometrial or stomach cancer, are also candidates. Genetic counseling evaluates the family history, determines the likelihood of an inherited syndrome, and explains the potential implications before testing.
Identifying a specific inherited syndrome allows healthcare providers to recommend specialized, frequent cancer surveillance. This proactive approach aims to find potential cancers at their earliest, most treatable stages, or to prevent them entirely.
Major Inherited Colon Cancer Syndromes
Inherited risk testing focuses on specific conditions that elevate colon cancer risk. The two most common hereditary syndromes, Lynch Syndrome and Familial Adenomatous Polyposis (FAP), account for the majority of inherited colon cancer cases.
Lynch Syndrome is the most frequently identified syndrome, caused by an inherited change in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2). The lifetime risk for colon cancer can be as high as 80%, depending on the gene affected, and is characterized by a low number of colon polyps. Individuals with Lynch Syndrome are also at increased risk for several other cancers, including endometrial, ovarian, and stomach cancers.
FAP is typically caused by a mutation in the APC gene and is defined by the development of hundreds to thousands of adenomatous polyps in the colon and rectum. If left untreated, the lifetime risk of developing colon cancer approaches 100%, often occurring before age 50. Attenuated FAP, a less severe form, involves fewer polyps but still carries a significantly increased cancer risk.
Genetic Testing of Existing Tumors
Genetic testing performed on the tumor tissue after a colon cancer diagnosis is called somatic testing. This is distinct from germline testing, as it looks for acquired genetic changes that occurred only within the cancer cells, not the patient’s inherited DNA. The primary purpose of somatic testing is to guide treatment decisions and predict the tumor’s behavior.
A primary application is assessing the tumor’s microsatellite instability (MSI) status, which indicates a defect in the mismatch repair pathway. Tumors identified as MSI-High may be eligible for immunotherapy, a type of treatment that harnesses the body’s immune system to attack the cancer cells. Somatic testing also looks for mutations in genes like KRAS, NRAS, and BRAF, which determine the effectiveness of targeted therapies, such as epidermal growth factor receptor (EGFR) inhibitors.
The presence or absence of these somatic mutations provides oncologists with information to tailor chemotherapy and targeted drug regimens. For example, a KRAS gene mutation is associated with resistance to EGFR-inhibitor drugs, making the test a necessary step before prescribing that class of medication. This personalized approach improves outcomes by matching the therapy to the tumor’s unique genetic profile.
Interpreting Results and Subsequent Actions
Interpreting genetic test results leads directly to specific, actionable medical recommendations for the patient and their family. A positive germline test for a syndrome like Lynch Syndrome or FAP triggers recommendations for intensified surveillance. This includes colonoscopies starting at a much younger age and performed more frequently than for the general population.
In FAP cases, the recommended action may include prophylactic surgery, such as surgical removal of the colon, to eliminate the near 100% lifetime cancer risk. For relatives, genetic counseling and cascade testing are recommended to determine who else in the family carries the mutation. Negative relatives revert to general screening guidelines, while positive relatives begin the intensive surveillance protocol.
Somatic tumor testing results provide a direct guide for cancer treatment. Identifying a tumor as MSI-High suggests that immunotherapy is an effective treatment option. Conversely, finding a RAS mutation rules out the use of certain targeted therapies, steering the oncologist toward more appropriate choices. These results ensure the patient receives the most effective, personalized medical plan for their specific cancer.