No Metachronous Cancers Observed in MSH6 and PMS2 Carriers
Douglas K. Rex, MD, MASGE, reviewing Andresdottir AK, et al. Gastroenterology 2023 Feb 16.
Lynch syndrome is caused by germline mutations in MLH1, MSH2, MSH6, or PMS2 genes, but the most commonly affected genes are MLH1 and MSH2. Increasingly, surveillance recommendations are on a gene-specific basis, with more intense surveillance recommended for MLH1 and MSH2 carriers and less for MSH6 or PMS2 carriers.
Iceland is in a unique situation for Lynch syndrome. In 2017, researchers identified Lynch syndrome in Iceland when they discovered the most common cause of Lynch syndrome is founder mutations in MSH6 and PMS2genes and that these mutations dominate Lynch syndrome in Iceland. Therefore, Iceland provides an opportunity to study the natural history of colorectal cancer (CRC) in Lynch syndrome caused by mutations in these 2 genes.
This study utilized the Icelandic Cancer Registry, which is complete back to 1955, to retrospectively identify patients with Lynch syndrome-associated cancers, none of whom underwent colonoscopic surveillance during 1955 to 2017, the studied period. Despite that, among 59 patients with CRC associated with MSH6 or PMS2, no metachronous CRC occurred.
These data are said to support recent recommendations to initiate colonoscopy at age 35 in MSH6 or PMS2carriers unless a family history of earlier cancers is present, and that surveillance intervals of 2 to 3 years for MSH6 carriers and 5 years for PMS2 carriers are adequate.
COMMENTEmphasis on this gene-specific approach in Lynch syndrome is increasing. My sense is that we are generally overdoing surveillance colonoscopy for Lynch syndrome in the U.S., particularly as adenoma detection rates continue to rise.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S)
Andresdottir AK, Einarsson H, Jonsdottir H, Jonasson JG, Bjornsson ES, Haraldsdottir S. Metachronous colorectal cancers in Icelandic MSH6 and PMS2 Lynch syndrome carriers in 1955-2017: a population-based study. Gastroenterology 2023 Feb 16. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2023.02.007)
