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.

Image Credit: CDC on Unsplash

The Colon Cancer Foundation (CCF) spoke with Alessandro Mannucci, MD, who received the 2022 Colon Cancer Foundation and CGA Colorectal Cancer Research Scholar Award to present his work at the 2022 CGA-IGC Annual Meeting in Nashville, TN, November 11-13. Dr. Mannucci, a medical resident in gastroenterology and gastrointestinal endoscopy at the San Raffael Hospital, Milan, Italy, will be presenting his work titled ‘Lynch Syndrome is Associated with Fecal and Salivary Dysbiosis’.

CCF: What is the importance of the gut and the microbial flora in the human body, and how do they influence our well-being?

Dr. Mannucci: Broadly speaking, the microbiota is made up of many different cell types, including bacteria, viruses, fungi, and other kinds of microorganisms. However, our study specifically focused on bacteria because it is known that we have way more bacteria in our body than human cells. That alone indicates the significant impact of the microbiome on different phases of our life—from childhood to adulthood. 

The disruption of a healthy microbiome equilibrium causes the components of the microbiome to converge toward a proinflammatory environment in several ways. Certain species increase the risk of colorectal cancer [CRC]. Organisms that increase in numbers in the presence of CRC are generally proinflammatory. This understanding has come simultaneously with the realization that inflammation is one of the new pillars of cancer. The inflammatory environment is a disruption that is particularly important when studying the colon because the colon is the first organ in direct contact with the microbiome. 

CCF: Can you tell us the importance of this fact in your research? 

Dr. Mannucci: In our study, we had a suspect: the microbiome. While the microbiome is known to play a role in turning a normal cell cancerous, this association had not been investigated in the context of the hereditary Lynch syndrome [LS]. Mutations in one of five genes can lead to LS. 

There is a spectrum of manifestations of LS, the most important of which is CRC, although developing the cancer is determined by penetrance. We were interested in knowing if the microbiome has a role in this process.We wanted to know if the microbiome in individuals with LS who had not yet developed cancer, differed from those without LS. While it may be difficult to explain a cause-and-effect relationship, it is important to understand why a difference exists. Germline pathogenic variants may influence the formation, conformation, and diversity of the microbiome, or vice versa. Interestingly, we found that the fecal microbiota was significantly different among those with LS, but we need more data.

CCF: What is the relevance of microorganisms in the oral cavity? 

Dr. Mannucci: In individuals with LS, the cells within their mouth are also mutated. So we decided to test the differ

 Alessandro Mannucci, MD

ence between the fecal and oral microbiota among those with and without LS and found that not only is the fecal microbiota different, which you would expect because LS is associated with an increased risk of CRC, but we also observed a proinflammatory change in the oral microbiota. We now know that the oral microbiota of patients with LS differs from that of healthy individuals, which raises the question that pathogenic variants inside the mouth may interact with microbiota species that cause a proinflammatory shift. 

Another hypothesis is that individuals with this particular hereditary predisposition to CRC may also have a predisposition to orthodontic diseases. While we currently have limited understanding of this association and are testing the hypothesis, our discovery of the unexpected difference of a proinflammatory environment led us to suppose that maybe something else was at play.

What is interesting when we talk about scientific studies is not only what you are interested in, but also what you compare it to. In our case, we compared LS patients without cancer diagnosis to unrelated, healthy patients. So we did not have within-family control, which other investigators might want to look at–within the family or individuals with LS in different age groups.

CCF: How long will the subjects in your study be followed?

Dr. Mannucci: While we usually follow patients throughout their lives, five to ten years of follow-up will give us more insight. The idea is that if there is a proinflammatory environment within that patient, it could trigger cancer at an earlier age. To test that hypothesis, we are collecting samples of relatively young individuals, and we want to follow them and see if they develop cancer. The mean age of patients with LS was 48 years plus or minus 16 years.

CCF: Does diet influence microbial flora and the balance of pro- versus anti-inflammatory microbial flora in the oral cavity and the gut?

Dr. Mannucci: You raise a very, very interesting point! The microbiota is adaptable, and it can change very rapidly. There is some robustness to it, meaning you shape the health of your microbiome during your youth and by the time you reach adolescence or young adulthood, your microbiota is pretty much set. However, it can change based on your diet. 

One of our study limitations is that we could not control for diet. We could control other factors that can influence the changes within the microbiota itself, such as age, sex, smoking, the presence of cancer, or chemotherapy treatment—factors that can modify the shape, overall biodiversity, and the general composition of the microbiota.

However, we could not control the overall dietary composition. In the future, we may control our patients’ diet and place them either on a Western diet as opposed to a Mediterranean diet or a modern diet. 

Assuming that individuals with a higher risk of CRC follow an anti-inflammatory diet, you would expect to see an anti-inflammatory microbiota. We found the opposite; we found a proinflammatory change within the microbiota. While we are planning to control for participant diets in future studies, an alternative approach would be to include individuals with different genetic backgrounds and eating similar diets to investigate the differences in their microbiota. 

But remember, this is currently a hypothesis. What we know now is that these genetic predispositions are associated with a difference in the microbiota composition, and that difference itself is a proinflammatory environment. We don’t know the cause-effect relationship or how that can be altered, yet.

CCF: What would be a key takeaway from your study findings?

Dr. Mannucci: A key takeaway is that we’re developing a tool to better understand who does or does not get cancer. Hopefully, it will become a tool or a target to reduce the risk of cancer. I completely agree that diet can be a big influence. So maybe in the near future, we will be able to tell our patients that if they stop smoking, regularly exercise, reduce the intake of fatty foods, and if they have a specific kind of diet, they can reduce their risk of CRC. The microbiota has the potential to become an instrument for reducing the risk of cancer, but we are not there yet.

Thank you to Sahar Alam, CCF’s Colorectal Cancer Prevention Intern, for her assistance with this post.

Early-stage colon cancer is treatable and has a very promising survival rate. However, less than 40% of new colon cancer diagnoses are early-stage disease. Now, a new study has identified an association of distance, region, and insurance coverage with advanced colon cancer at initial diagnosis. Utilizing the Nation Cancer Database, patients 18 years or older diagnosed with colon cancer as a primary diagnosis between 2010 and 2017 were compared in terms of distance to their medical facility, region of residence, and insurance coverage. 

The study found that patients at an increased risk of advanced pathologic disease:

  • Traveled a greater distance to their medical facility
  • Lived in the Northeast, Mountain, or Central regions of the United States
  • Only had Medicaid or did not have insurance coverage

 

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