Risk Communication: Information for the Clinician about Colorectal Cancer Risk

Risk Factors for Colorectal Cancer

Non-modifiable Risk Factors

Age.  Incidence of colorectal cancer rises rapidly with age.  90% of cases of CRC are diagnosed in individuals older than 50. (45)  The incidence in those 65 and over is almost 20 times that of those under 65.  This makes age a much stronger risk factor than any of the personal health or lifestyle factors identified to date and discussed below.

Because of the strong relationship of age to colorectal cancer, early detection is most effective in older men and women.  However, it is crucial to convey that early detection of colorectal cancer can increase the chance of survival at any age; screening should begin at age 50 in average risk patients, even though the risk is less at age 50 than at age 70.  Routine fecal occult blood test (FOBT) can reduce the risk of dying from colorectal cancer by approximately 30% (16).

Personal history of adenomatous polyps.   A personal history of adenomatous polyps increases an individual’s risk of developing colorectal cancer.  Histology of the polyps is critical: tubulovillous and villous adenomatous polyps have the greatest malignant potential.  Individuals with tubulovillous or villous adenomatous polyps and those with adenomas greater than 1 cm are three times more likely to progress to CRC than those without such polyps.  The National Polyp Study (NPS) revealed that removal of adenomatous polyps leads to a 76-90% decrease in the risk of developing CRC. (17)  People found to have polyps on screening require more frequent follow-up; the NPS suggests that about a third of people with adenomatous polyps removed during colonoscopy will be found to have additional polyps at three years. (43)

Family history of adenomatous polyps.  Individuals with a family history of adenomatous polyps in a first-degree relative (parent or sibling) have a 1.9 fold increased risk of developing CRC.(18)

Personal or family history of CRC.  Persons with a personal history of CRC are at an increased risk of recurrence and development of new colorectal malignancies.  In addition, according to a meta-analysis of studies of familial risk, a family history of colorectal cancer in one first-degree relative (parent, sibling, child) increases a person's risk by 2-3 fold.  Those with two affected first-degree relatives have a risk approximately 4 times greater than the average risk population.  In general, personal risk declines as the age of the affected family member increases, so that a diagnosis in a relative under 45 increases personal risk 3.8 times, while a diagnosis in a relative over age 59 increases personal risk only about 1.8 times.  Colon cancer in a second-degree relative appears to increase risk by a lesser extent, about 1.5 times the average-risk population.(18) 

Inflammatory Bowel Disease.  Individuals with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer, and the risk increases with the duration of IBD.  The precise relative risk is not known.  Studies differ in terms of duration of disease, advances in treatment may make earlier statistics inapplicable, and certain patients may have higher risk than others. (19)  For ulcerative colitis, a 2002 meta-analysis offered cumulative cancer incidence rates of 1.6% after 10 years of disease, 8.3% after 20 years, and 18.4% after 30 years.  More recent studies suggest lower cumulative incidence.  The apparent decline may be due to treatment and increased vigilance, including medical therapy, surgery, and colonscopic surveillance.  (35)

Studies of cancer in Crohn's disease also show increased risk, but the magnitude varies widely and many of these studies predate current treatments.  Duration of disease, extent of disease, involvement of the colon, and presence of colonic strictures all appear to increase risk. (36)

Genetic Syndromes. Certain genetic syndromes predispose individuals to the development of colorectal cancer.  Familial adenomatous polyposis (FAP) is an inherited or acquired germline defect in the adenomatous polyposis coli (APC) gene.  Mutations in this gene result in the presence of thousands of adenomas blanketing the colon, with a nearly 100% risk of developing CRC. Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant defect known to result from a germline mutation. The Finnish Cancer Registry revealed that 82% of people who carried this genetic defect developed CRC by age 70. (18)  CRC typically arises in the right colon in individuals with HNPCC and appears at a younger age (<50 years).  HNPCC is also associated with the appearance of multiple cancers in family members.  The following extracolonic tumors may be found: endometrial, gastric, ovarian, hepatobiliary, urinary tract and small bowel.  While diagnosis of HNPCC may be less obvious than that of FAP since it may resemble sporadic cancer, the presence of cancer in multiple first-degree relatives is a valuable clue.