EVIDENCE-BASED ANSWER
THE BEST APPROACH HINGES on the number, degree, and age of relatives diagnosed with colorectal cancer (CRC) or adenomatous polyps (AP). Screening should begin at 40 years of age for patients with a family history of CRC or AP in at least 1 first-degree relative or CRC in at least 2 second-degree relatives (strength of recommendation [SOR]: B, extrapolation from systematic reviews).
Patients at highest risk—who have 1 first-degree relative diagnosed with CRC or AP before 60 years of age or multiple first-degree relatives diagnosed at any age—should begin screening with colonoscopy at 40 years of age or 10 years younger than the earliest affected relative and undergo a repeat colonoscopy every 5 years (SOR: C, consensus guidelines).
Patients who have a first-degree relative diagnosed with CRC or AP after 60 years of age or 2 or more second-degree relatives with CRC should start screening at 40 years of age, with routine options and follow-up intervals (SOR: C, consensus guidelines). (Routine options and follow-up intervals include any of the following 3 regimens: annual high-sensitivity fecal occult blood testing, sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years, or screening colonoscopy every 10 years.1)
Evidence summary
Prospective studies and systematic reviews show increased risk for CRC in people with a significant family history. Little or no data are available regarding outcome improvements or head-to-head comparisons of the effects of different screening methods. Recommendations for screening rest largely on inference and consensus opinions.
Family history=higher risk at lower age
The US Preventive Services Task Force (USPSTF) recommends CRC screening starting at 50 years of age for patients with average risk, based on a 5.6% lifetime risk of developing CRC and good evidence that screening reduces morbidity and mortality.1 Patients with a family history of CRC or AP have a risk of CRC at 40 years of age that approximates average risk at 50 years.2 Right-sided colonic lesions are also more likely in patients with a family history of CRC (relative risk [RR]=2.25; 95% confidence interval [CI], 1.96-2.59).3
Risk increases with number of affected first-degree relatives
Moreover, systematic reviews show the RR of CRC to be 1.99 (95% CI, 1.55-2.55) in patients with a single first-degree relative with AP, 2.25 (95% CI, 2.00-2.53) with a single first-degree relative with CRC, and 4.25 (95% CI, 3.01-6.02) with 2 or more first-degree relatives with CRC.3
Younger age at diagnosis also increases risk
The effect of the relative’s age at diagnosis of CRC is demonstrated by an RR of 3.87 (95% CI, 2.40-6.22) if diagnosed at younger than 45 years, 2.25 (95% CI, 1.85-2.72) if diagnosed at 45 to 59 years, and 1.82 (95% CI, 1.47-2.25) if diagnosed at 60 years or older.3
Recommendations
Colonoscopy is the preferred screening option for most patients with family histories that put them at increased risk of CRC and right-sided colonic lesions.4,5 The American Cancer Society (ACS) and the American Gastroenterological Association (AGA) recommend that patients with a first-degree relative diagnosed before the age of 60 years or 2 or more first-degree relatives with CRC are at highest risk and should undergo colonoscopy at age 40, or 10 years before the earliest relative’s age at diagnosis; colonoscopy should be repeated every 5 years.4,5
Patients with a first-degree relative diagnosed with CRC or AP at 60 years or older or multiple second-degree relatives with CRC have an increased risk, but lower than the high-risk group.4 Such patients may start screening early, at 40 years, but using the same options as patients at average risk (see the Evidence-Based Answer).4 The TABLE summarizes these screening recommendations. Notably, the ACS recommends no screening change (from patients with average risk) for patients with CRC in second-degree relatives because of the modest increase in risk.5
TABLE
ACS and AGA guidelines for screening patients with a family history of colorectal cancer
| Risk factor | Screening method | Age to start | Surveillance |
|---|---|---|---|
| CRC or AP in 1 first-degree relative diagnosed at <60 yr or multiple first-degree relatives | Colonoscopy | 40 yr, or 10 yr before earliest age at diagnosis of an affected relative | Repeat every 5 years |
| 1 first-degree relative with CRC diagnosed at ≥60 yr or ≥2 second-degree relatives with CRC | Same as average-risk screening* | 40 yr | Same as average-risk screening |
| 1 second-degree or any more distant relatives with CRC | Same as average-risk screening | Same as average-risk screening | Same as average-risk screening |
| *The ACS recommends screening these patients as average risk, meaning that screening should occur at age 50 and can use other recommended screening methods besides colonoscopy. | |||
| ACS, American Cancer Society; AGA, American Gastroenterological Association; AP, adenomatous polyps; CRC, colorectal cancer. | |||
| Adapted from: Winawer S et al. Gastroenterology. 2003 and Smith RA et al. CA Cancer J Clin. 2003.5 | |||