A previous, nonrandomized study from Finland showed that among patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome), mortality was significantly lower in those who underwent colonoscopic surveillance at 3-year intervals than in those who were not screened (JW Gastroenterol Jul 1 2000).

To assess the effectiveness of 1- to 2-year surveillance intervals recommended in the Netherlands for Lynch syndrome patients, investigators examined colorectal cancer (CRC) incidence rates in 745 patients (from 205 families) with genetically established Lynch syndrome who had undergone at least two colonoscopies since 1995. Lynch syndrome was identified by mismatch repair gene mutations in MLH1 (75 families), MSH2 (87 families), or MSH6 (43 families). The mean follow-up was 7.2 years, and the mean surveillance interval between examinations was 16 months.

The results were as follows:

• Thirty-three patients (4.4%) developed CRC under surveillance.
• Patients 40 showed a nonsignificant trend toward greater risk for CRC than younger patients (P=0.06).
• MSH6 carriers showed a nonsignificant trend toward lower risk for CRC compared with MSH2 and MLH1 carriers (0.8% vs. 4.0% and 6.6%, respectively; P=0.07).
• The risk for developing CRC was 6% in patients examined under the 1- to 2-year surveillance interval recommended in the Netherlands since 1995; that figure was reduced from a 10% risk among patients examined under the older surveillance-interval standard of 2 to 3 years.
• Of the patients whose CRCs were detected within 2 years of surveillance colonoscopy, 90% were confined to the bowel wall (Dukes stage A or B).

A cohort of patients with family histories of CRC, but no mismatch repair gene mutations for Lynch syndrome (called familial CRC type X), had a substantially lower risk for CRC during surveillance and a lower risk for extracolonic tumors than did mutation carriers. A surveillance interval of at least 3 years might be adequate for such patients.

Comment: The results of this nonrandomized study support current U.S. screening guidelines, which recommend that adults with Lynch syndrome undergo colonoscopy every 2 years until age 40 and then annually thereafter. The findings also suggest that identifying the specific mismatch repair gene mutation in a given family might eventually be used to help stratify risk for CRC.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology July 9, 2010