DNA

Colorectal cancer (CRC) is the fourth leading cause of cancer and second leading cause of mortality from cancer in the United States. As the population ages, decisions regarding the initiation and cessation of screening and surveillance for CRC are of increasing importance. In elderly patients, the risks of CRC and the presenting signs and symptoms are similar to those in younger patients. Screening and ongoing surveillance should be considered in patients who have a life expectancy of 10 years or more. Life expectancy estimates can be calculated using online calculators. If screening is deemed appropriate, the choice of which test to use first is unclear. Currently, there are a number of modalities available to screen for CRC, including both invasive modalities (eg, colonoscopy, sigmoidoscopy, capsule colonoscopy, and computed tomographic colonography) and noninvasive modalities (fecal immunochemical test, stool DNA testing, and blood testing). Colonoscopy and other invasive testing options are considered safe, but the risks of complications of the bowel preparation, the procedure, and sedation medications are all increased in older patients. In contrast, noninvasive testing provides a safe initial test; however, it is important to consider the increased false-positive rates in the elderly, and a positive test result will usually necessitate colonoscopy to establish the diagnosis. Ongoing screening and surveillance should be a shared decision-making process with the patient based on multiple factors including the patient’s morbidity and mortality risk from CRC and his or her underlying comorbidities, the patient’s functional status, and the patient’s preferences for screening. Ultimately, the decision to initiate or discontinue screening for CRC in older patients should be done based on a case-by-case individualized discussion.

Mendelian disorders and monogenic traits result from combinations of variants in 1 or a few genes that have a large effect on the propensity for developing a certain disease or characteristic. In contrast, complex traits, such as eye color or cardiovascular disease, are determined by variations occurring in many genes that have smaller effect sizes and act over long periods of time, often in concert with environmental factors. The cumulative risk derived from aggregating contributions of the many DNA variants associated with a complex trait or disease is referred to as a polygenic risk score (also known as a genetic risk score). This JAMA Genomics and Precision Health article explains polygenic risk scores as determinants of an individual’s inherited risk for complex disease.