Risk of Metachronous Colorectal Cancer in Lynch Syndrome: Who Needs an Extended Resection?

Abstract

Lynch syndrome (LS) is the most common genetic condition associated with early-onset colorectal cancer. It is inherited in an autosomal dominant fashion. The increased cancer risk is due to a germline mutation in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene. This leads to a deficient DNA mismatch repair mechanism, resulting in the accumulation of nucleotide changes and microsatellite instability, providing phenotypical evidence that MMR is not functioning normally. LS is associated with a high risk of early-onset colorectal cancer and recurrence. Thus, when undergoing surgery for primary colorectal cancer, extended resection should be discussed with the patient. This review provides an overview of current surgical risk-reducing strategies in LS-associated colorectal cancer. Surgical treatment for LS carriers with colorectal cancer needs to be highly individualized, based on patient and disease characteristics. Strategies are presented to guide decision making in pathologic MMR gene mutation carriers undergoing surgery for colorectal cancer.