A Schedule for Colorectal Cancer Screening Among Patients With Lynch Syndrome on the Basis of Mutation Status

Colorectal cancer,medical anatomical illustration
Lynch syndrome is associated with 4 genetic variants that increase risk of CRC, thereby necessitating updated screening guidelines for these variants.

A timeline for genetic variant-specific surveillance strategies for patients with Lynch syndrome (LS) was published in Gastroenterology.

With data available in the literature, researchers from Columbia University Irving Medical Center developed a Markov model which predicted the transition to colorectal cancer (CRC) on the basis of variant status. The genes which were incorporated into this model were MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and PMS1 homolog 2 mismatch repair system component (PMS2). Remission was not included in this model.

Without intervention, the investigators used lifetime cancer incidence rates of 57.46% for MLH1, 47.65% for MSH2, 18.66% for MSH6, and 9.20% for PMS2 mutation carriers and mortality rates of 15.54%, 10.21%, 3.06%, and 1.66%, respectively.

Among patients with an MLH1 mutation, the model replicated the current guidelines that colonoscopy should begin at age 25 with surveillance every 2 years. This strategy corresponded with 29.51 quality-adjusted life years (QALYs) at a total cost of $40,783.80, corresponding with an incremental cost effectiveness ratio (ICER) of $44,790.96. With this strategy, CRC incidence was 17.04% with 46.48 life-years gained.

For MSH2, the surveillance strategy was the same as for MLH1. With this schedule, incidence was 16.57% and 46.64 life-years were gained. The total cost was $32,261.21 and ICER was $29,298.71. The current guidelines stated that surveillance should occur every year. This was not found to be cost-effective (ICER, $2,009,850.42), despite the lower incidence rate (13.27%).

The optimal strategy for MSH6 was surveillance every 3 years beginning at age 35. The QALYs was 29.892 for this scenario with an incidence rate of 6.56% and 46.84 life-years gained. The total cost was $14,072.41. The current guidelines stated surveillance should start at age 25 years, but this was not cost-effective (ICER, $246,980.73).

The patients with PMS2 mutations should not begin surveillance until age 40. This strategy had 29.941 QALYs, an ICER of $2,216.81, incidence of 3.25%, and increased life-years of 46.89.

This study was limited by the paucity of data about carriers of PMS2 and MSH6 mutations (studies on both include patient cohorts <850 patients).

This model found that among patients with LS, carriers of MLH1 and MSH2 mutations should be screened for CRC every 2 years beginning at age 25, those with MSH6 variants every 3 years at age 35, and carriers of PMS2 mutations every 3 years at age 40.


Kastrinos F, Ingram MA, Silver ER, et al. Gene-specific variation in colorectal cancer surveillance strategies for Lynch syndrome. Gastroenterol. Published online April 9, 2021. doi: 10.1053/j.gastro.2021.04.010