Risk of deficient mismatch repair colorectal cancer and precursors after kidney transplantation: a nationwide study

Abstract

Colorectal cancer (CRC) incidence rises posttransplant, though the mechanism remains unclear. We hypothesize that impaired immunosurveillance of kidney transplant recipients (KTRs) allows progression along the serrated pathway, increasing only immunogenic deficient mismatch repair (dMMR) CRC incidence and not proficient mismatch repair CRC. The nationwide transplant, pathology, and cancer registries were linked by probabilistic matching to retrieve data of all KTRs in the Netherlands. Standardized incidence ratios (SIRs) were calculated. Premalignant lesions were identified within the Dutch CRC screening program, and KTRs were matched to controls. Among 15 013 KTRs, 109 CRCs were observed between 2015 and 2021, resulting in an SIR of 1.22 (95% confidence interval [CI]: 0.99-1.47). The median time from transplantation to CRC was 7.9 years (interquartile range: 4.2-13.6). dMMR CRC occurred in 31% of KTRs, significantly higher than the general CRC population’s 13%, with an SIR of 3.09 (95% CI: 2.23-4.30). Incidence of proficient mismatch repair CRC was not increased, and the SIR was 0.94 (95% CI: 0.75-1.18). Sessile serrated lesions with dysplasia occurred 2.9-fold more often in KTRs than matched controls (95% CI: 1.7-5.1). An increased dMMR CRC risk post–kidney transplantation and increased prevalence of the immediate precursor sessile serrated lesion with dysplasia were demonstrated.