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Screening for colorectal cancer in patients with a family history of colorectal cancer

Scott D Ramsey, MD
William M Grady, MD
Section Editors
J Thomas Lamont, MD
Joann G Elmore, MD, MPH
Deputy Editor
Judith A Melin, MA, MD, FACP


Colorectal cancer (CRC) results from both genetic and environmental factors and their interaction. Genetic predisposition is the dominant risk factor for a small proportion of individuals; however, environmental factors (including diet, exercise, smoking, and obesity) are stronger risk factors in most people [1,2]. A family history of CRC is common among the general population. In the United States, between 5 and 10 percent of adults (aged 20 to 79 years) report having a first-degree relative with CRC [3]; other countries have reported rates that are somewhat higher, with one study from the Netherlands reporting that 11.7 percent of adults aged 30 to 70 years had at least one first-degree relative with CRC [4]. This rate increases with age, reflecting the increasing chance that relatives will develop CRC as they get older.

One in four patients with CRC is at moderately increased risk because of a family history [5]. Approximately 3 to 4 percent of patients with newly diagnosed CRC have very high risk due to a cancer susceptibility syndrome caused by one of two autosomal dominant, highly penetrant genetic mutations:

Lynch Syndrome, also called hereditary nonpolyposis colon cancer (HNPCC), accounts for about 2 to 3 percent of CRC and an increased risk of other cancers as well [6,7]. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis".)

Familial adenomatous polyposis (FAP) accounts for less than 1 percent of CRC; cancers are preceded by hundreds of polyps throughout the colon. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis".)

Less frequent hereditary syndromes with increased risk for CRC include MUTYH-associated polyposis (MAP), juvenile polyposis syndrome, Cowden syndrome, Li-Fraumeni syndrome, attenuated familial adenomatous polyposis (AFAP), Peutz-Jeghers syndrome, and serrated (hyperplastic) polyposis syndrome. It is likely that the remainder of the heritable risk for CRC, usually called "familial" or "nonsyndromic familial" CRC, results from one or more genetic polymorphisms with a higher prevalence, but lower penetrance, than genes for Lynch syndrome or FAP. The interaction of these polymorphisms with environmental carcinogens is hypothesized to lead to CRC. After genetic and environmental factors, another important nongenetic risk for CRC is inflammatory bowel disease. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors".)

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Literature review current through: Sep 2017. | This topic last updated: Jul 11, 2017.
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