The National Cancer Institute (NCI) published an article indicating that since the mid-1980 and 1990's, colon cancer incidence rates have decreased in individuals 55 and older, while increasing in adults ages 20-50. This new evidence has prompted a discussion as to whether screening should start earlier than the current recommendation of 50 years old in a person with average risk. Recommendations for earlier screening have already been established for high-risk individuals, i.e. individuals with a first degree relative diagnosed with colorectal cancer before age 60.
With the exclusion of skin cancers, the American Cancer Society reports colorectal cancer as the third most common cancer diagnosed in both men and women in the United States. The lifetime risk of developing colorectal cancer is about 1 in 21 for men and 1 in 23 for women; therefore earlier screening may increase prevention and lower the lifetime risks.
Individuals with a personal and/or family history of an inherited colorectal cancer syndrome have a higher risk than the general population to develop colorectal cancer, therefore screening is recommended at a much earlier age which can be specific to each syndrome. There are several syndromes associated with hereditary colorectal cancer. The three most common are Lynch syndrome, familial adenomatous polyposis (FAP), and MYH-associated polyposis (MAP), which account for up to 5% of all colon cancer cases.
With an incidence of approximately 1 in 400 to 1 in 500, Lynch syndrome is the most common form of inherited colorectal cancer, and approximately 3% of all colon cancers are Lynch syndrome. Formerly referred to as hereditary non-polyposis colorectal cancer (HNPCC), individuals with Lynch syndrome have an increased risk of developing more than one cancer. Women with Lynch syndrome have increased risks of developing endometrial and ovarian cancers, and both men and women with Lynch syndrome have an increased risk of developing gastric cancer. Other cancers associated with Lynch syndrome include brain, hepatobiliary, and urinary tract cancers. Pathogenic variants in the MLH1, MSH2, MSH6, EPCAM, and PMS2 genes are causes of Lynch syndrome. The current recommendation for surveillance is to begin colonoscopies between ages 20 -25 or two to five years before the earliest diagnosis in the family, whichever is earlier.
Familial Adenomatous Polyposis
Familial adenomatous polyposis (FAP) is characterized by the development of hundreds to thousands of colonic polyps. 95% of individuals with FAP develop polyps by age 35. FAP is an autosomal dominant condition and is caused by pathogenic variants in the APC gene. APC sequencing is recommended after a clinical diagnosis consistent with FAP or an APC-associated polyposis condition (attenuated FAP and Gardner syndrome). In individuals known to have FAP, a colonoscopy or sigmoidoscopy is recommended beginning between 10 -15 years old.
MYH-associated polyposis (MAP) is an autosomal recessive disorder characterized by the development of multiple polyps in the colon, stomach, or duodenum, and an increased risk for cancer. MAP is caused by pathogenic variants in the MUTYH gene. Testing of the MUTYH gene is recommended for individuals with a suspected clinical diagnosis of FAP or attenuated FAP, in whom no APC pathogenic variant was identified. If an individual has a biallelic MUTYH mutation or is the sibling of a patient with MAP, the recommendation is to begin colonoscopy screening between ages 25-30.
Genetic Testing for Colorectal Cancer
Having a family health history or personal history of tumors, colon polyps and/or colon cancer, especially before age 50, are key indications for genetic testing. Determining which gene to test first, in the clinical suspicion of Lynch syndrome, can be a little tricky. Thanks to research and organizations like the American College of Medical Genetics and Genomics (ACMG), genetic testing algorithms have been developed to assist genetic professionals in testing for Lynch syndrome, FAP, MAP, and other colorectal cancer syndromes. Below you can find a much simplified version of the algorithm for Lynch syndrome reported in the ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer. Also, click the article to view the testing algorithm for FAP and MAP.
March is National Colorectal Cancer Awareness Month. Two prominent advocacy organizations dedicated to helping those with colorectal cancer are the National Colon Cancer Alliance and Hereditary Colon Cancer (HCC) Takes Guts. The National Colon Cancer Alliance provides funding for research and high-quality patient support resources. HCC Takes Guts provides patients and medical professionals with resources (educational webinars and pamphlets) and information about specific inherited colorectal cancer syndromes.
Interested in genetic testing for inherited colorectal cancer? Click each on the syndrome below to view single-gene tests and panel tests offered by EGL Genetics:
What is the best way to locate a genetic counselor to discuss your risks for developing cancer? The National Society of Genetic Counselors (NSGC) provides a searchable directory of genetic counselors in the United States and Canada. Click the link to visit the NSGC directory: http://www.nsgc.org/page/find-a-gc-search.
2. Hegde M et al. ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genetics in Medicine (2014) 16, 101-116.
3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Genetic/Familial High-Risk Assessment: Colorectal. Version 2.2016.