Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case–control study

Roel M. M. Bogie, Chantal M. C. le Clercq, Quirinus J. M. Voorham, Martijn Cordes, Daoud Sie, Christian Rausch, Evert van den Broek, Sara D. J. de Vries, Nicole C. T. van Grieken, Robert G. Riedl, Prapto Sastrowijoto, Ernst-Jan Speel, Rein Vos, Bjorn Winkens, Manon van Engeland, Bauke Ylstra, Gerrit A. Meijer, Ad A. M. Masclee*, Beatriz Carvalho

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case–control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. Results: In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). Conclusion: Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. Clinical trial registration: NTR3093 in the Dutch trial register (

Original languageEnglish
JournalBritish Journal of Cancer
Early online date2021
Publication statusE-pub ahead of print - 2021

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