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Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Major Genetic Syndromes

Table 8. Clinical Practice Guidelines for Diagnosis and Colon Surveillance of Familial Adenomatous Polyposis (FAP) continued...

In other series, the risk of developing adenomas in an MMR gene mutation carrier has been reported to be 3.6 times higher than the risk in noncarriers.[217] By age 60 years, 70% of the carriers developed adenomas, compared with 20% of noncarriers. As previously mentioned, these mutation carriers developed adenomas at an earlier age than noncarriers. Most of the adenomas in carriers had absence of MMR protein expression and were more likely to have dysplastic features, compared with adenomas from control subjects.[217] Given that colonoscopy is the accepted measure for colon cancer surveillance, preliminary data suggest that the use of chromoendoscopy, such as with indigo carmine, may increase the detection of diminutive, histologically advanced adenomas.[327,328]

Although screening the intact colon is usually recommended for at-risk LS family members, some patients, faced with the high risk of CRC and the fallibility of screening, elect to undergo risk-reducing colectomy. However, there is a risk of developing cancer in the remaining rectum.[329]

Level of evidence: 3a

Table 9 summarizes the clinical practice guidelines from different professional societies regarding diagnosis and surveillance for LS.

Table 9. Practice Guidelines for Diagnosis and Colon Surveillance of Lynch Syndrome

Organization Tumor MSITumor IHCMMR Mutation TestingAge Screening InitiatedFrequencyMethodComments
C = colonoscopy; GI = gastrointestinal; IHC = immunohistochemistry; MMR = mismatch repair; MSI = microsatellite instability; NA = not addressed; NCCN = National Comprehensive Cancer Network.
a GI Societies – American Academy of Family Practice, American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine, American College of Radiology, American Gastroenterological Association, American Society of Colorectal Surgeons, and American Society for Gastrointestinal Endoscopy.
American Cancer Society[133]NANACounseling to consider genetic testing21 y1–2 y until age 40 y, then annuallyC 
American Society of Colon and Rectal Surgeons[134,135,136]YesYesYesNANANA 
Europe Mallorca Group[330]YesYesYes20–25 y; consider stopping at age 80 y1–2 yCDespite acknowledging that existing data support a 3 y screening interval, this group elected to recommend a shorter screening interval.
GI Societiesa [130]NANANA20–25 y1–2 yC 
NCCN[84]YesYesYes20–25 y OR 2–5 y prior to the youngest age at diagnosis in the family if it is before age 25 y; whichever comes first1–2 yCFamilies in whom a tumor has shown informative IHC and MSI, but no germline mutation found, should have at-risk relatives screened as if they were mutation carriers.

Chemoprevention in LS

The Colorectal Adenoma/Carcinoma Prevention Programme (CAPP2) was a double-blind, placebo-controlled, randomized trial to determine the role of aspirin in preventing CRC in patients with LS who were in surveillance programs at a number of international centers.[331] The study randomly assigned 861 participants to aspirin (600 mg/day), aspirin placebo, resistant starch (30 g/day), or starch placebo for up to 4 years. At a mean follow-up of 55.7 months (range: 1–128 mo), 53 primary CRCs developed in 48 participants (18 of 427 in the aspirin group and 30 of 434 in the aspirin placebo group). Seventy-six patients who refused randomization to the aspirin groups (due to aspirin sensitivity or history of peptic ulcer disease) were randomly assigned to receive resistant starch or resistant starch placebo. The intention-to-treat analysis yielded an HR for CRC of 0.63 (95% CI, 0.35–1.13; P = .12). However, five of the patients who developed CRC developed two primary colon cancers. A Poisson regression was performed to account for the effect of the multiple primary CRCs and yielded a protective effect for aspirin (incidence rate ratio [IRR], 0.56; 95% CI, 0.32–0.99; P = .05). For participants who completed at least 2 years of treatment, the per-protocol analysis yielded an HR of 0.41 (95% CI, 0.19–0.86; P = .02) and an IRR of 0.37 (0.18–0.78; P = .008). An analysis of all LS cancers (endometrial, ovarian, pancreatic, small bowel, gall bladder, ureter, stomach, kidney, and brain) revealed a protective effect of aspirin versus placebo (HR, 0.65; 95% CI, 0.42–1.00; P = .05). There were no significant differences in adverse events between the aspirin and placebo groups, and no serious adverse effects were noted with any treatment. The authors concluded that 600 mg of aspirin per day for a mean of 25 months substantially reduced cancer incidence in LS patients. A limitation of the trial is that the frequency of surveillance studies at the various centers was not reported as being standardized. Earlier CAPP2 trial results for 746 LS patients enrolled in the study were published in 2008 [332] and failed to show a significant preventive effect on incident colonic adenomas or carcinomas (relative risk [RR], 1.0; 95% CI, 0.7–1.4) with a shorter mean follow-up of 29 months (range: 7–74 mo). The CAPP3 trial, which will evaluate the effect of lower doses of aspirin, is expected to begin in 2013.

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Last Updated: February 25, 2014
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