Adenomas and Beyond: Colonoscopy Surveillance, Racial and Socioeconomic Disparities in Lynch Syndrome.

Pathogenic variants in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2) cause Lynch syndrome; the risk of colorectal precancerous lesions and its kinetics differ according to the gene involved.

This retrospective cohort of 187 patients with Lynch syndrome examined the occurrence of adenomas, sessile serrated lesions and colorectal cancer according to race, socioeconomic status and the mismatch repair gene involved. The commonest subtype was MSH6 (31.0%); at first colonoscopy, 23% of patients had sessile serrated lesions, 8.6% had adenomas and 17.1% had colorectal cancer. No difference in adenoma or sessile serrated lesion occurrence was seen by race or socioeconomic status, but lower socioeconomic status was associated with greater odds of colorectal cancer at first colonoscopy (odds ratio 1.24; 95% CI 1.01-1.52). Among patients with a normal first colonoscopy, the odds of adenoma or sessile serrated lesion during follow-up were higher for MSH6 carriers than for MLH1 (hazard ratio 3.71; 95% CI 1.08-12.78) and MSH2 carriers (hazard ratio 9.52; 95% CI 2.32-39.11), whereas lesions were most frequent among MSH2 carriers at first colonoscopy.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The striking finding is the reversal of hierarchy between first colonoscopy and follow-up: MSH2 highest at entry, MSH6 highest during follow-up, which argues against relaxing surveillance intervals in an MSH6 carrier whose first colonoscopy is normal — precisely the opposite of the usual clinical temptation. Confidence intervals are nonetheless very wide (up to 39.11 for MSH2) in a retrospective single-cohort study of 187 patients: the direction of effect is more credible than its magnitude, and this is not enough to rewrite recommended intervals. The socioeconomic signal for colorectal cancer at first colonoscopy points mainly to delayed access to screening, something worth asking about explicitly in consultation.

Analysis by Dr Thibaut Benquey