COLARIS AP ®
Adenomatous Polyposis Colon Cancer SyndromesThe most common adenomatous polyposis conditions are thought to account for approximately 2% of all colon cancer. They can be categorized into three conditions: familial adenomatous polyposis, attentuated familial adenomatous polyposis and MYH-associated polyposis. Classic familial adenomatous polyposis (FAP) and attentuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene. The APC gene is a tumor suppressor gene which regulates cellular growth and proliferation. Both FAP and AFAP are inherited in an autosomal dominant manner. MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene. MAP is inherited in an autosomal recessive manner. Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as "biallelic MYH mutations"). Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected). The MYH gene is an important part of the base excision repair (BER) pathway, which allows for repair of DNA mutations caused by oxidative damage to cells. MAP is believed to account for approximately 1% of all colorectal cancers. MAP can cause patients to develop colorectal cancer even in the absence of colon polyposis. When assessing hereditary cancer risk, a patient's personal and family history is collected to investigate the risk for a polyposis syndrome. Once a patient is identified as being at increased risk for one of these syndromes, genetic test results provide the most accurate means of cancer risk assessment for a patient. It is important to note that approximately 20% to 30% of FAP cases are caused by new mutations, meaning that an APC germline mutations may be present in an individual even if it is absent in both parents.5 Also, due to the autosomal recessive inheritance pattern of MAP, many affected patients have no relatives with colorectal polyps or cancer. Genetic testing is the only way to identify truly at-risk family members.
Identifying Patients at Risk of Adenomatous Polyposis SyndromesFinding patients at risk for adenomatous polyposis syndromes and following up with them is perhaps the most critical step in changing hereditary cancer outcomes. The following red flags in a patient's personal or family history indicate an increased risk for a germline mutation in APC or MYH and help determine appropriate candidates for testing:
- Individuals clinically affected with FAP (100 or more colorectal adenomas)
- Individuals with multiple colorectal adenomas (usually 10 or more cumulative adenomas)
- Relatives of APC or MYH mutation carriers
COLARIS AP® TestingCOLARIS AP® testing assesses a person’s risk of developing hereditary colorectal polyps and cancer. COLARIS AP® detects mutations in the APC and MYH genes, which cause adenomatous polyposis colon cancer syndromes, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MYH-associated polyposis (MAP).
Benefits of COLARIS AP® TestingThe results of the COLARIS AP® test enable the development of a patient-specific medical management plan to significantly reduce the risk of cancer. COLARIS AP® will help you to:
- Target increased surveillance and other interventions specifically to individuals with the APC or MYH gene mutations—maximizing patient care and increasing clinical efficiency
- Improve patient compliance with tailored screening recommendations and preventive measures
- Significantly improve outcomes and reduce medical costs through early diagnosis and treatment of cancer, should it develop. An individual’s risk for developing colorectal cancer can be reduced by nearly 100% with appropriate preventive measures in FAP. Avoid unnecessary interventions involving family members who do not test positive for the mutation(s)
- Counsel patients and their family members on the underlying cause of the cancer or adenomas
- Avoid unnecessary interventions involving family members who do not test positive for the mutation(s) known to be in the family
- Differentiate between AFAP, MAP, and Lynch syndrome
Managing Patients with Adenomatous Polyposis SyndromesIt is possible to change the outcome for patients who have adenomatous polyposis syndromes. If a COLARIS AP® test result confirms the presence of adenomatous polyposis syndromes, the following medical management options may help reduce or even eliminate the risk of cancer. Familial Adenomatous Polyposis (FAP): Increase Surveillance:
- Annual flexible sigmoidoscopy beginning between ages 10 and 12.
- Following a prophylactic subtotal colectomy, flexible sigmoidoscopy of remaining ileal pouch and rectal epithelium every 6 months to 3 years, depending on number of polyps found on previous exam.
- Esophagogastroduodenoscopy (EGD) every 1 to 4 years (depending on polyp burden), beginning between age 20 and 25.
- Annual physical exam, including palpation of the thyroid, beginning between age 10 and 12.
- Research to determine the effectiveness of NSAIDS in colorectal polyp development is currently being conducted
- The FDA has approved some NSAIDS to help prevent polyp formation in the rectum after a total colectomy, but none of these drugs are proven to reduce or prevent polyps prior to surgery
- Prophylactic total colectomy is advised following development of adenomatous polyps
- For patients who have MAP, medical society management recommendations include colonoscopies every 1-2 years starting at age 25-30, upper endoscopies every 3-5 years starting at age 30-35, and surgical considerations. The most appropriate medical management will vary based upon your patient’s clinical presentation.
- For MYH mutation carriers (1 mutation), medical management should be determined by clinical findings and personal and family history of colorectal polyps and/or cancer. Current data are limited but suggest that any increase in risk, if present, is likely to be small.
Screening Recommendations for Extracolonic Manifestations of FAP and AFAP
|Duodenal and Gastric Cancer||20-25||EGD||Every 1-4 Years|
|Thyroid Cancer||10-12||Physical Exam||Annual|
|Hepatoblastoma||Birth to age 5||Serum AFP, Imaging||Annual|