factors, including an unhealthy diet, insufficient physical activity, high alcohol consumption, and smoking.80 These behaviors are traditionally associated with high-income countries, where CRC rates are highest. On a global scale, increasing CRC incidence is considered a marker of economic transition.81 Importantly, however, numerous studies have shown that people with healthy lifestyle behaviors have a 27% to 52% lower risk of CRC compared to those without these behaviors.82 Nonmodifiable factors that increase risk are related to heredity and medical history, including a personal or family history of CRC or adenomas (precancerous polyps) and a personal history of long-term chronic inflammatory bowel disease. Most people at increased risk because of a medical or family history should begin CRC screening before age 45. (For more information on CRC screening guidelines, please see page 30.) The following sections present current knowledge about factors associated with CRC risk. Heredity and family history Up to 30% of CRC patients have a family history of the disease, making this one of the most important and actionable risk factors.83-85 People with a first-degree relative (parent, sibling, or child) who has been diagnosed with CRC have 2 to 4 times the risk of developing the disease compared to people without this family history, with higher risk for diagnosis before age 50 and/or multiple affected relatives (Table 3).84 However, a history of CRC among more distant relatives also increases risk,86 as does a family history (first- or second-degree relatives) of adenomas.87 Much of the CRC clustered in families is thought to reflect interactions between lifestyle factors and the cumulative effect of relatively common genetic variations that increase disease risk, referred to as high prevalence/low penetrance mutations.88 Identification of families with a history of CRC, especially high-burden families with undiagnosed genetic syndromes (i.e., low prevalence/high penetrance mutations, described below), offers substantial opportunity to lessen cancer incidence and mortality through increased surveillance with colonoscopy. However, patient family history in medical records continues to be incomplete. One study found that less than half of primary care physicians documented information about family members other than first-degree relatives, and age at cancer diagnosis was rarely collected.89 Another study found that only 22% of CRC patient medical records had family history information sufficient to identify individuals who should be referred for genetic counseling and/or testing.90 Table 3. Relative Risks for Established Colorectal Cancer Risk Factors Relative risk* Factors that increase risk: Heredity and medical history Family history84 CRC 1 or more first-degree relatives 2.2 1 or more first-degree relatives diagnosed before age 50 3.6 2 or more first-degree relatives 4.0 1 or more second-degree relatives 1.7 Adenoma 1 or more first-degree relatives 2.0 Inflammatory bowel disease115 1.7 Type 2 diabetes124 Male 1.4 Female 1.2† Modifiable factors Heavy alcohol (daily average >3 drinks)195 1.3 Obesity (body mass index ≥30 kg/m2 ) 146 1.3 Colon, male 1.5 Colon, female 1.1 Rectum, male 1.3 Rectum, female 1.0† 1.1 1.2 Red meat (100 g/day)166 Processed meat (50 g/day)166 Smoking190 Current vs. never 1.5 Former vs. never 1.2 Factors that decrease risk: Physical activity138 0.7 Dairy (400 g/day)166 0.9 *Relative risk compares the risk of disease among people with a particular “exposure” to the risk among people without that exposure. Relative risk for dietary factors compares the highest with the lowest consumption. If the relative risk is more than 1.0, then risk is higher among exposed than unexposed persons. Relative risks less than 1.0 indicate a protective effect. †Relative risk was not statistically significant. ©2020, American Cancer Society, Inc., Surveillance Research 14 Colorectal Cancer Facts & Figures 2020-2022 Hereditary syndromes A recent study found that 5% of CRC patients have an inherited gene mutation (germline mutation) associated with a known high-risk hereditary condition, and an additional 5% have mutations associated with moderately increased risk.91 Lynch syndrome The