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

R.M.M. Bogie, C.M.C. le Clercq, Q.J.M. Voorham, M. Cordes, D. Sie, C. Rausch, E. van den Broek, S.D.J. de Vries, N.C.T. van Grieken, R.G. Riedl, P. Sastrowijoto, E.J. Speel, R. Vos, B. Winkens, M. van Engeland, B. Ylstra, G.A. Meijer, A.A.M. Masclee*, B. Carvalho

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalBritish Journal of Cancer
Volume126
Issue number6
Early online date15 Dec 2021
DOIs
Publication statusPublished - 1 Apr 2022

Keywords

  • ISLAND METHYLATOR PHENOTYPE
  • MICROSATELLITE INSTABILITY
  • CHROMOSOME INSTABILITY
  • SERRATED PATHWAY
  • ADENOMA
  • RISK
  • PREVALENCE
  • MORTALITY
  • NEOPLASMS
  • RESECTION

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