SURVEILLANCE FOR HNPCC

NEW YORK (Reuters Health) Mar 11 - Performing colonoscopies every 1 to 2 years rather than every 2 to 3 years reduces the risk of colorectal cancer in families with Lynch syndrome from 10% to 6%, according to a new study.

Lynch syndrome is an autosomal dominant disorder caused by defects in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2. The mutations increase patients' risk for colon and other cancers. While frequent colonoscopy screenings are recommended for Lynch syndrome families, there is no consensus as to the optimal interval, with recommendations ranging from annually to every 2 to 3 years. This new study from The Netherlands compares benefits of intensive, 1 to 2 year surveillance to 2 to 3 year surveillance.

Using the national Dutch Lynch syndrome registry, the researchers identified 745 mutation carriers from 205 Lynch syndrome families. In addition, they identified 344 individuals from 46 families with non-Lynch colorectal cancer (at least 3 relatives with colorectal cancer, with at least two being first-degree relatives, and two successive affected generations).

The researchers observed both groups from 1995 to 2009, screening the Lynch carriers at intervals averaging 16 months.

After a mean of roughly 7 years, colorectal cancer developed in 6 (1.7%) non-Lynch subjects and 33 Lynch mutation carriers (4.4%). The cumulative risk of colorectal cancer in the Lynch carriers was 6% at 10 years, where studies with 2 to 3 year surveillance intervals have reported cumulative risks of around 10%.

"Our study shows that 1 to 2 year surveillance intervals significantly lower the risk of developing colorectal cancer under surveillance," said Dr. H. F. A. Vasen, medical director of The Netherlands Foundation for the Detection of Hereditary Tumors and the lead author on the study.

Lynch patients with MLH1 and MSH2 mutations had the highest risks for colorectal cancer -- 6.6% and 4.0%, respectively -- whereas only 1 out of 127 MSH6 carriers developed colorectal cancer (0.8%). Patients 40 years or older at the start of the evaluation also demonstrated higher risk, but the difference was not statistically significant.

"The study is important because it allows us to individualize the recommendations: annual colonoscopies in carriers of a MLH1 and MSH2 mutation older than 40 years, and biannual...colonoscopies in younger patients (for example less than 35-40 years) and carriers of MSH6 mutation," Dr. Vasen told Reuters Health by e-mail.

The study was published online in Gastroenterology on March 4th.

Gastroenterology 2010.