most common hereditary risk factor for CRC is Lynch syndrome, which accounts for about 3% of all CRCs.91 People with Lynch syndrome are also at increased risk for many other cancers, including endometrial, ovarian, small intestine, stomach, urinary bladder, and female breast.92 These individuals have a mutation in certain genes that hinders the cell’s ability to correct errors introduced during DNA replication. These mistakes result in additional mutations that can ultimately lead to cancer,93 the likelihood of which is dependent on which gene is affected. Among the 80% of Lynch syndrome patients with high-risk gene (MLH1 or MSH2) mutations, 19% to 25% will develop CRC by age 50 and 40% will develop the disease by age 70.94 The median age at CRC diagnosis among Lynch syndrome patients is 61 years of age,95 and 8% of CRCs that occur in adults younger than age 50 are caused by Lynch syndrome.96 Although an estimated 1.2 million Americans (1 in 279) have Lynch syndrome,97 the vast majority are undiagnosed because identification is dependent on a cancer diagnosis. However, there is increasing recognition of the need for a more proactive approach because rigorous colonoscopy surveillance leads to early-stage diagnosis and high survival in Lynch syndrome patients.98 Numerous organizations, including the National Comprehensive Cancer Network and American Society for Clinical Oncology, recommend testing for Lynch snydrome in all patients with colorectal or endometrial cancer.99, 100 Although implementation of universal testing has been slow in the community hospital setting,101 most major public and private insurers cover the screening.102 Polyposis syndromes Polyposis syndromes are another type of hereditary condition associated with increased CRC risk, the most common of which is familial adenomatous polyposis (FAP), which accounts for about 1% of all CRCs.91 FAP is characterized by the development of up to thousands of colorectal polyps in the second and third decade of life. It is typically caused by a mutation in the adenomatous polyposis coli (APC) gene, which normally prevents uncontrolled cell growth and division.103 These mutations are usually inherited, but occur spontaneously in 10% to 25% of affected people so there is not always a family history of the condition.104 Disease severity ranges from severe (classic FAP) to mild (attenuated FAP), with the latter associated with later age at onset and fewer polyps (90% of polyps can be safely 20 Colorectal Cancer Facts & Figures 2020-2022 removed during colonoscopy, elective surgery to remove nonmalignant polyps, which has a higher risk of harms, increased by more than 50% from 2000 to 2014.231 Other limitations of colonoscopy include a higher risk of complications compared to other screening tests, such as bowel tears and bleeding, especially when a polyp is removed or patients are older.230, 231 Although these side effects are rare, serious bleeding occurs in 1 to 2 of every 1,000 colonoscopies.225, 232, 233 In addition, colonoscopy sometimes misses adenomas, especially those that are located in the proximal colon; those that occur in high-risk patients; and those that are flat (sessile adenomas), from which 20% to 30% of CRCs are thought to originate.226, 234 The quality of colonoscopy, which is variable in the US, is also associated with missed lesions, which sometimes progress to CRC before the next scheduled exam (i.e., Table 4. Characteristics of Recommended Colorectal Cancer Screening Tests Benefits Performance & Complexity* Limitations Test Time Interval Visual Examinations Colonoscopy • Examines entire colon • Can biopsy and remove polyps • Can diagnose other diseases • Required for abnormal results from all other tests Performance: Highest Complexity: Highest • Full bowel cleansing • Can be expensive • Sedation usually needed, necessitating a chaperone to return home • Patient may miss a day of work. • Highest risk of bowel tears or infections compared with other tests 10 years† Computed tomographic colonography (CTC) • Examines entire colon • Fairly quick • Few complications • No sedation needed • Noninvasive Performance: High (for