Hereditary Colon Cancer: Guide for Health Pros

Approximately 5 to 10 percent of colon cancer is hereditary. The major hereditary colon cancer syndromes are Lynch syndrome (previously known as Hereditary Non-Polyposis Colorectal Cancer or HNPCC) and Familial Adenomatous Polyposis (FAP). Other genes have also been implicated in hereditary colon cancer risk.

The genetic risk assessment service at UT Southwestern Simmons Comprehensive Cancer Center offers testing and genetic counseling for colon cancer and all other identified cancers. Based on an individual’s personal and family history of cancer, our genetic counselors can identify the level of risk, determine if genetic testing is appropriate, and provide guidance for an early detection and prevention strategy.

Watch a video about hereditary colon cancer management.

Colon Cancer Facts

One in 18 individuals (5.5 percent) will develop colon cancer in their lifetime. Of all colon cancer cases, only about 5 to 10 percent are hereditary, linked to gene mutations inherited from one’s mother or father.

Multiple genes are associated with hereditary colon cancer, but mutations in genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) are the most common cause of the hereditary form of the disease. Prediction models can estimate an individual’s risk for a Lynch syndrome mutation.

Additional information on colon cancer predisposition genes can be found on the Hereditary Colon Cancer Gene List listed below.

Approximately 25 to 35 percent of colon cancer is familial, meaning the disease occurs more often in family members than can be expected in the general population even though a particular gene mutation has not been identified in the family. With familial colon cancer, the specific cause of colon cancer is unknown but likely due to combinations of risk factors including genetics, lifestyle, and environment that increase risk in the family.

Screening recommendations vary for individuals with an increased lifetime risk for colon cancer based on a hereditary cancer syndrome or family history.

The remainder of colon cancer diagnoses (around 70 percent) are considered random or sporadic and non-hereditary, without a known etiology. Risk factors for sporadic colon cancer include: 

• Age (9 out of 10 people are over age 50)
  
• Inflammatory bowel disease, ulcerative colitis, Crohn’s disease
  
• Diets high in fat and/or low in fiber
  
• Smoking/tobacco use 
  
• Physical inactivity and/or obesity
  
• Type 2 diabetes
  

Genes

Management of High-Risk Patients

The National Comprehensive Cancer Network (NCCN) has established and published guidelines for cancer care that are focused on quality, effectiveness, and efficiency. The guidelines are continuously updated to reflect current research. Specific recommendations for screening and management of individuals with an increased lifetime risk of cancer due to hereditary colon cancer syndromes are briefly summarized below. Please note that most current and detailed guidelines are available through NCCN “Genetic/Familial High-Risk Assessment: Colorectal.”

NCCN recommendations for high-risk colon cancer genes, including genes implicated in Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) and polyposis genes (APC, MUTYH), have been established (NCCN v1.2015).

For Lynch syndrome, the surveillance guidelines do vary based on the gene in question:

• MLH1/MSH2/EPCAM mutation carriers are advised to start colonoscopy every 1 to 2 years starting at age 20 to 25, women are recommended to consider prophylactic TAHBSO after childbearing (typically age 35 to 40), and upper endoscopy can be considered every 3 to 5 years starting at age 35 based on family history or in Asian populations due to their elevated gastric cancer risk.
  
• For MSH6/PMS2 mutation carriers, colonoscopy is advised starting at age 25 to 30 every 1 to 2 years, prophylactic hysterectomy should be considered after age 40, and other cancer screening can be considered based on family history (these are thought to be lower than MLH1/MSH2 risks).
  
• For APC, colonoscopy or flexible sigmoidoscopy is recommended annually starting age 10 to 15 until polyp burden is too great to clear effectively (at this point, total colectomy recommended); upper endoscopy starting at age 20 to 25 to evaluate stomach and duodenum; annual thyroid exam starting in the late teens; desmoid risk warrants annual abdominal palpation with possible imaging if needed.
  
• For MUTYH, annual colonoscopy starting by age 21 or based on family history (if polyp burden too great to clear with colonoscopy, colectomy can be considered) with baseline upper endoscopy by age 35.
  
• Other high-risk genes related to colon cancer include Peutz-Jeghers syndrome, juvenile polyposis, serrated polyposis syndrome, Li-Fraumeni syndrome and Cowden syndrome (PTEN Hamartoma Tumor syndrome).
  

NCCN also publishes colon cancer screening recommendations based on increased risk due to family history (Colorectal Cancer Screening v1.2015). Recommendations are based on number of first- or second-degree relatives diagnosed with colon cancer and ages at diagnosis. A first-degree relative with an advanced adenoma is also a consideration for altered colonoscopy screening recommendations. Individuals at an increased risk should discuss this information with their physicians to establish an appropriate screening routine.

Prediction Models for Hereditary Colon Cancer Risk

At Simmons Comprehensive Cancer Center, we use a variety of assessment tools designed to predict an individual’s likelihood of Lynch syndrome (LS). Statistical models have not been developed to predict risk for other hereditary colon cancer syndromes at this time. Not all tools can be appropriately applied to all patients. Each tool is most effective when the patient’s characteristics and family history are similar to those of the study population on which the tool was based. All have limitations, and the risk estimates derived from the tools may differ for an individual patient.