Colorectal cancer occurs when the cells in the large intestines (colon) or rectum begin to grow abnormally into a malignant tumor. About 5% of cases are inherited (hereditary colorectal cancer), while most are not. Hereditary colorectal cancer (HCC) occurs when a person has a genetic change (mutation) that causes their cells to be more likely to become cancerous. The mutation can be passed through generations in a family. Women and men with HCC have a higher risk of developing colorectal cancer, and sometimes other cancers or health problems, as well.

Our genes, or DNA, tell the cells in our body how to work correctly. Cancer-risk genes are genes with roles that can impact whether a cell will begin to grow uncontrollably into cancer. We have two copies of every gene, one from our mother and the other from our father. Hereditary colorectal cancer is most commonly inherited in an autosomal dominant way. For dominant conditions, having only one copy of a gene mutation is enough to cause symptoms. In the case of HCC, having one mutation leads to an increased risk for cancer. If a person has a mutation in one gene for HCC, there is a 50% risk that each of their children will inherit this mutation. Siblings, parents, and potentially other relatives could also have the mutation. Importantly, not everyone who has a mutation in a cancer-risk gene will develop cancer, but their chances are higher. While rare, it is possible for a person to have a mutation for a dominant condition that is absent from both of their parents. In this situation, the mutation arose early before they were conceived or born. This is called de novo inheritance. Even after de novo inheritance, if a person has a mutation in one gene for hereditary colorectal cancer, each of their children will have a 50% risk to inherit the mutation. Less commonly, HCC can be inherited in an autosomal recessive way. For recessive conditions, both copies of a person’s gene must have a mutation before they will have an increased risk for cancer. Typically, an individual with a recessive condition will have inherited one mutation from their mom and one from their dad. Because the mom and dad have another copy of the gene without the mutation, they will usually not show symptoms. For these parents, there is a 25% risk with each pregnancy that the child will inherit both the mom’s and the dad’s mutations, and therefore, will have the recessive condition. Similarly, for a person with recessive HCC to have an affected child, their partner would also need to have a mutation in the same cancer-risk gene. A genetic counselor can help with partner testing in this situation. What are hereditary colorectal cancer syndromes? Hereditary colorectal cancer syndromes are conditions that impact other areas of an individual’s body in addition to increasing their risk for colorectal cancer. A syndrome can be inherited in a dominant, de novo, or recessive manner. Two common hereditary colorectal cancer syndromes are Lynch syndrome and Familial Adenomatous Polyposis (FAP), and each is described below: Lynch Syndrome: Lynch syndrome, also known as Hereditary Non-polyposis Colorectal Cancer (HNPCC), is caused by a mutation in a gene whose job is to repair the DNA damage that normally occurs as cells grow and divide. About 1 in 30 cases of colorectal cancer are linked to this condition. People with Lynch syndrome have up to an 80% risk to develop colon cancer by age 70 years. They are also at an increased risk for many other types of cancers, such as endometrial, gastric, and prostate. Familial Adenomatous Polyposis (FAP): People with FAP develop hundreds of benign growths (polyps) in their intestines and rectum. Because these polyps can become cancerous, the chance someone with FAP will eventually develop colorectal cancer is near 100%. With such a high risk for cancer, screening by colonoscopy may be started in childhood, and preventative surgery to remove the colon is common.

• Known cancer-risk gene mutation in the family
• Colorectal or endometrial cancer diagnosed before age 50 years
• Diagnosis of colorectal cancer and more than 10 adenomas
• Diagnosis of colorectal cancer with a pathology evaluation that suggests Lynch syndrome

POSITIVE:

 A positive result means that a genetic mutation causing an increased risk for colorectal cancer was identified. Your risk for other cancers or health conditions may also be increased, depending on the gene involved. Your doctor can use this information to customize your care, which could include increased screening, preventative surgery, medication, and other steps. A positive result is also important for your family. Your parents, siblings, and children could have as high as a 50% chance to also have the mutation. As a result, sharing your genetic testing results with your relatives is important for their health.

NEGATIVE:

 A negative result indicates that a genetic mutation was not identified. A negative result may indicate that there is not a cancer-risk gene mutation in you or your family. However, it can also mean that the gene increasing risk in you or your family was not included on the ordered test, or that it may not be currently known. Your doctor can use a negative result to continue your treatment and screening based on your clinical and family history, or they may consider another type of genetic testing.

VARIANT OF UNCERTAIN CLINICAL SIGNIFICANCE (VUS):

The third possible test result is called a Variant of Uncertain Clinical Significance. A gene variant is a genetic difference that could be disease-causing (mutation) or could be a normal finding (benign). More research is needed to determine whether the variant is important or not, and it should be treated as a negative result until more information is available. Your doctor may follow up with the laboratory in the future to see if more has been learned.

Hereditary colorectal cancer syndromes are conditions that impact other areas of an individual’s body in addition to increasing their risk for colorectal cancer. A syndrome can be inherited in a dominant, de novo, or recessive manner. Two common hereditary colorectal cancer syndromes are Lynch syndrome and Familial Adenomatous Polyposis (FAP), and each is described below:

Lynch Syndrome:

 Lynch syndrome, also known as Hereditary Non-polyposis Colorectal Cancer (HNPCC), is caused by a mutation in a gene whose job is to repair the DNA damage that normally occurs as cells grow and divide. About 1 in 30 cases of colorectal cancer are linked to this condition. People with Lynch syndrome have up to an 80% risk to develop colon cancer by age 70 years. They are also at an increased risk for many other types of cancers, such as endometrial, gastric, and prostate

 Familial Adenomatous Polyposis (FAP):

People with FAP develop hundreds of benign growths (polyps) in their intestines and rectum. Because these polyps can become cancerous, the chance someone with FAP will eventually develop colorectal cancer is near 100%. With such a high risk for cancer, screening by colonoscopy may be started in childhood, and preventative surgery to remove the colon is common.

• a diet that is low in fiber
• high alcohol consumption
• having had breast, ovary, or uterine cancer
• a family history of colorectal cancer
• having ulcerative colitis, Crohn’s disease, or irritable bowel disease (IBD)
• overweight and obesity
• smoking
• a lack of physical activity
• The presence of polyps in the colon or rectum, as these may eventually become cancerous.