Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

        Abstract
        
          Objective
          To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants.
        
        
          Methods
          
            CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (
            path_MMR)
            followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred
            path_MMR
            carriers who were first- or second-degree relatives of Lynch syndrome probands.
          
        
        
          Results
          
            In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in
            path_MLH1
            carriers at 70 years of age were 52% in males and 41% in females; for
            path_MSH2
            50% and 39%; for
            path_MSH6
            13% and 17% and for
            path_PMS2
            11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups.
          
        
        
          Conclusions
          
            Prospectively observed CRC incidences (PLSD) in
            path_MLH1
            and
            path_MSH2
            carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in
            path_MSH6
            carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in
            path_PMS2
            carriers subjected to colonoscopy, but not significantly so.

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

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