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Clinical Studies

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

British Journal of Cancer volume 126, pages 865–873 (2022)Cite this article

Subjects

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.

Clinical trial registration

NTR3093 in the Dutch trial register (www.trialregister.nl).

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Fig. 1: Flowchart of the process of selection of CRC cases for molecular analysis.
Fig. 2: Comparison of molecular features between post-colonoscopy colorectal cancers (PCCRCs) and detected colorectal cancers (DCRCs).
Fig. 3: Unsupervised hierarchal cluster analysis based on the molecular features of all CRCs analysed.

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Data availability

The sequencing data used in this study are available in the European Genomes and phenomes Archive (ega-archive.org), with provisory number EGAS00001004686.

References

  1. Singh S, Singh PP, Murad MH, Singh H, Samadder NJ. Prevalence, risk factors, and outcomes of interval colorectal cancers: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109:1375–89. https://doi.org/10.1038/ajg.2014.171

    Article  PubMed  Google Scholar 

  2. Rex DK. Preventing colorectal cancer and cancer mortality with colonoscopy: what we know and what we don’t know. Endoscopy. 2010;42:320–3. https://doi.org/10.1055/s-0029-1244067

    Article  CAS  PubMed  Google Scholar 

  3. le Clercq CM, Sanduleanu S. Interval colorectal cancers: what and why. Curr Gastroenterol Rep. 2014;16:375. https://doi.org/10.1007/s11894-014-0375-3

    Article  PubMed  Google Scholar 

  4. Pabby A, Schoen RE, Weissfeld JL, Burt R, Kikendall JW, Lance P, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc. 2005;61:385–91.

    Article  Google Scholar 

  5. le Clercq CM, Bouwens MW, Rondagh EJ, Bakker CM, Keulen ET, de Ridder RJ, et al. Postcolonoscopy colorectal cancers are preventable: a population-based study. Gut. 2014;63:957–63. https://doi.org/10.1136/gutjnl-2013-304880

    Article  PubMed  Google Scholar 

  6. Robertson DJ, Lieberman DA, Winawer SJ, Ahnen DJ, Baron JA, Schatzkin A, et al. Colorectal cancers soon after colonoscopy: a pooled multicohort analysis. Gut. 2014;63:949–56. https://doi.org/10.1136/gutjnl-2012-303796

    Article  PubMed  Google Scholar 

  7. Rondagh EJ, Bouwens MW, Riedl RG, Winkens B, de Ridder R, Kaltenbach T, et al. Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention. Gastrointest Endosc. 2012;75:1218–25. https://doi.org/10.1016/j.gie.2012.02.010

    Article  PubMed  Google Scholar 

  8. Kudo S, Lambert R, Allen JI, Fujii H, Fujii T, Kashida H, et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 2008;68:S3–47. https://doi.org/10.1016/j.gie.2008.07.052.

    Article  PubMed  Google Scholar 

  9. Bogie RMM, Veldman MHJ, Snijders LARS, Winkens B, Kaltenbach T, Masclee AAM, et al. Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and risk of submucosal invasion: a meta-analysis. Endoscopy. 2018;50:263–82.

  10. Oka S, Tanaka S, Saito Y, Iishi H, Kudo SE, Ikematsu H, et al. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol. 2015;110:697–707. https://doi.org/10.1038/ajg.2015.96.

    Article  PubMed  Google Scholar 

  11. Hazewinkel Y, Lopez-Ceron M, East JE, Rastogi A, Pellise M, Nakajima T, et al. Endoscopic features of sessile serrated adenomas: validation by international experts using high-resolution white-light endoscopy and narrow-band imaging. Gastrointest Endosc. 2013;77:916–24. https://doi.org/10.1016/j.gie.2012.12.018

    Article  PubMed  Google Scholar 

  12. O’Brien MJ, Zhao Q, Yang S. Colorectal serrated pathway cancers and precursors. Histopathology. 2015;66:49–65.

    Article  Google Scholar 

  13. Cisyk AL, Singh H, McManus KJ. Establishing a biological profile for interval colorectal cancers. Dig Dis Sci. 2014;59:2390–402. https://doi.org/10.1007/s10620-014-3210-7.

    Article  CAS  PubMed  Google Scholar 

  14. Sawhney MS, Farrar WD, Gudiseva S, Nelson DB, Lederle FA, Rector TS, et al. Microsatellite instability in interval colon cancers. Gastroenterology. 2006;131:1700–5. https://doi.org/10.1053/j.gastro.2006.10.022

    Article  PubMed  Google Scholar 

  15. Arain MA, Sawhney M, Sheikh S, Anway R, Thyagarajan B, Bond JH, et al. CIMP status of interval colon cancers: another piece to the puzzle. Am J Gastroenterol. 2010;105:1189–95. https://doi.org/10.1038/ajg.2009.699

    Article  PubMed  Google Scholar 

  16. Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N. Engl J Med. 2013;369:1095–105. https://doi.org/10.1056/NEJMoa1301969

    Article  CAS  PubMed  Google Scholar 

  17. Soong TR, Nayor J, Stachler MD, Perencevich M, Jajoo K, Saltzman JR, et al. Clinicopathologic and genetic characteristics of interval colorectal carcinomas favor origin from missed or incompletely excised precursors. Modern Pathol. 2018; e-pub ahead of print 21 November, 2018. https://doi.org/10.1038/s41379-018-0176-6

  18. Cisyk AL, Nugent Z, Wightman RH, Singh H, McManus KJ. Characterizing microsatellite instability and chromosome instability in interval colorectal cancers. Neoplasia. 2018;20:943–50. https://doi.org/10.1016/j.neo.2018.07.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Statline CBS. Bevolkingsontwikkeling; kevendgeborenen, overledenen en migratie per regio. 2011; http://statline.cbs.nl/statweb/.

  20. Rutter MD, Beintaris I, Valori R, Chiu HM, Corley DA, Cuatrecasas M, et al. World endoscopy organization consensus statements on post-colonoscopy and post-imaging colorectal cancer. Gastroenterology. 2018;155:909–25 e903. https://doi.org/10.1053/j.gastro.2018.05.038.

    Article  PubMed  Google Scholar 

  21. Carvalho B, Postma C, Mongera S, Hopmans E, Diskin S, van de Wiel MA, et al. Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression. Gut. 2009;58:79–89. https://doi.org/10.1136/gut.2007.143065

    Article  CAS  PubMed  Google Scholar 

  22. Scheinin I, Sie D, Bengtsson H, Van De Wiel MA, Olshen AB, Van Thuijl HF, et al. DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly. Genome Res. 2014;24:2022–32.

    Article  CAS  Google Scholar 

  23. Wanders LK, Cordes M, Voorham Q, Sie D, de Vries SD, d’haens G, et al. IBD-associated dysplastic lesions show more chromosomal instability than sporadic adenomas. Inflamm bowel Dis. 2019. https://doi.org/10.1093/ibd/izz171.

    Article  Google Scholar 

  24. Voorham QJ, Carvalho B, Spiertz AJ, van Grieken NC, Mongera S, Rondagh EJ, et al. Chromosome 5q loss in colorectal flat adenomas. Clin Cancer Res. 2012;18:4560–9. https://doi.org/10.1158/1078-0432.CCR-11-2385

    Article  CAS  PubMed  Google Scholar 

  25. Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–93.

    Article  CAS  Google Scholar 

  26. Derks S, Postma C, Moerkerk P, van den Bosch SM, Carvalho B, Hermsen MA, et al. Promoter methylation precedes chromosomal alterations in colorectal cancer development. Anal Cell Pathol. 2006;28:247–57.

    Article  CAS  Google Scholar 

  27. Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB, Methylation-specific PCR. a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996;93:9821–6.

    Article  CAS  Google Scholar 

  28. Van De Wiel MA, Smeets SJ, Brakenhoff RH, Ylstra B. CGHMultiArray: exact P-values for multi-array comparative genomic hybridization data. Bioinformatics. 2005;21:3193–4.

    Article  Google Scholar 

  29. van Buuren S, Groothuis-Oudshoorn K. MICE: multivariate imputation by chained equations in R. J Stat Softw. 2011;45:1–67.

    Article  Google Scholar 

  30. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2015.

  31. Dorenkamp S, Mesters I, Schepers J, Vos R, van den Akker M, Teijink J, et al. Disease combinations associated with physical activity identified: The SMILE Cohort Study. Biomed Res Int. 2016;2016:9053578. https://doi.org/10.1155/2016/9053578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Finch H. Comparison of distance measures in cluster analysis with dichotomous data. J Data Sci. 2005;3:85–100.

    Article  Google Scholar 

  33. Warnes GR, Bolker B, Bonebakker L, Gentleman R, Huber W, Liaw A, et al. gplots: Various R Programming Tools for Plotting Data [computer program]. Version 3.1.1. 2016. https://github.com/talgalili/gplots.

  34. Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487:330–7. https://doi.org/10.1038/nature11252

    Article  CAS  Google Scholar 

  35. Stoffel EM, Erichsen R, Froslev T, Pedersen L, Vyberg M, Koeppe E, et al. Clinical and molecular characteristics of post-colonoscopy colorectal cancer: a population-based study. Gastroenterology. 2016. https://doi.org/10.1053/j.gastro.2016.07.010.

  36. Cisyk AL, Penner-Goeke S, Lichtensztejn Z, Nugent Z, Wightman RH, Singh H, et al. Characterizing the prevalence of chromosome instability in interval colorectal cancer. Neoplasia. 2015;17:306–16. https://doi.org/10.1016/j.neo.2015.02.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;396:643–9. https://doi.org/10.1038/25292

    Article  CAS  PubMed  Google Scholar 

  38. Simons CC, Hughes LA, Smits KM, Khalid-de Bakker CA, de Bruine AP, Carvalho B, et al. A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis. Ann Oncol. 2013;24:2048–56. https://doi.org/10.1093/annonc/mdt076

    Article  CAS  PubMed  Google Scholar 

  39. JEIJ, Medema JP, Dekker E. Colorectal neoplasia pathways: state of the art. Gastrointest Endosc Clin North Am. 2015;25:169–82. https://doi.org/10.1016/j.giec.2014.11.004

    Article  Google Scholar 

  40. Fearon ER, Carethers JM. Molecular subtyping of colorectal cancer: time to explore both intertumoral and intratumoral heterogeneity to evaluate patient outcome. Gastroenterology. 2015;148:10–13. https://doi.org/10.1053/j.gastro.2014.11.024

    Article  PubMed  Google Scholar 

  41. Shaukat A, Arain M, Thaygarajan B, Bond JH, Sawhney M. Is BRAF mutation associated with interval colorectal cancers? Dig Dis Sci. 2010;55:2352–6. https://doi.org/10.1007/s10620-010-1182-9

    Article  CAS  PubMed  Google Scholar 

  42. Hoffmeister M, Blaker H, Jansen L, Alwers E, Amitay EL, Carr PR, et al. Colonoscopy and reduction of colorectal cancer risk by molecular tumor subtypes: a population-based case-control study. Am J Gastroenterol. 2020;115:2007–16. https://doi.org/10.14309/ajg.0000000000000819.

    Article  PubMed  Google Scholar 

  43. Okamoto K, Kitamura S, Kimura T, Nakagawa T, Sogabe M, Miyamoto H, et al. Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: current status and management. J Gastroenterol Hepatol. 2017;32:358–67. https://doi.org/10.1111/jgh.13482

    Article  PubMed  Google Scholar 

  44. Pohl H, Srivastava A, Bensen SP, Anderson P, Rothstein RI, Gordon SR, et al. Incomplete polyp resection during colonoscopy-results of the complete adenoma resection (CARE) study. Gastroenterology. 2013;144:74–80 e71. https://doi.org/10.1053/j.gastro.2012.09.043

    Article  PubMed  Google Scholar 

  45. Bettington M, Walker N, Rosty C, Brown I, Clouston A, McKeone D, et al. Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma. Gut. 2017;66:97–106. https://doi.org/10.1136/gutjnl-2015-310456

    Article  CAS  PubMed  Google Scholar 

  46. Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088–2100. https://doi.org/10.1053/j.gastro.2009.12.066

    Article  CAS  PubMed  Google Scholar 

  47. Voorham QJ, Rondagh EJ, Knol DL, van Engeland M, Carvalho B, Meijer GA, et al. Tracking the molecular features of nonpolypoid colorectal neoplasms: a systematic review and meta-analysis. Am J Gastroenterol. 2013;108:1042–56. https://doi.org/10.1038/ajg.2013.126

    Article  CAS  PubMed  Google Scholar 

  48. Voorham QJ, Carvalho B, Spiertz AJ, Claes B, Mongera S, van Grieken NC, et al. Comprehensive mutation analysis in colorectal flat adenomas. PLoS ONE. 2012;7:e41963. https://doi.org/10.1371/journal.pone.0041963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Konda K, Konishi K, Yamochi T, Ito YM, Nozawa H, Tojo M, et al. Distinct molecular features of different macroscopic subtypes of colorectal neoplasms. PLoS ONE. 2014;9:e103822. https://doi.org/10.1371/journal.pone.0103822

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sanduleanu S, Rondagh EJ, Masclee AA. Development of expertise in the detection and classification of non-polypoid colorectal neoplasia: experience-based data at an academic GI unit. Gastrointest Endosc Clin North Am. 2010;20:449–60. https://doi.org/10.1016/j.giec.2010.03.006

    Article  Google Scholar 

  51. Jover R, Zapater P, Polania E, Bujanda L, Lanas A, Hermo JA, et al. Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies. Gastrointest Endosc. 2013;77:381–9 e381. https://doi.org/10.1016/j.gie.2012.09.027.

    Article  PubMed  Google Scholar 

  52. le Clercq CM, Mooi RJ, Winkens B, Salden BN, Bakker CM, van Nunen AB, et al. Temporal trends and variability of colonoscopy performance in a gastroenterology practice. Endoscopy. 2016;48:248–55. https://doi.org/10.1055/s-0041-111117

    Article  PubMed  Google Scholar 

  53. Waldmann E, Gessl I, Sallinger D, Jeschek P, Britto-Arias M, Heinze G, et al. Trends in quality of screening colonoscopy in Austria. Endoscopy. 2016;48:1102–9. https://doi.org/10.1055/s-0042-113185.

    Article  PubMed  Google Scholar 

  54. Pilonis ND, Bugajski M, Wieszczy P, Franczyk R, Didkowska J, Wojciechowska U, et al. Long-term colorectal cancer incidence and mortality after a single negative screening colonoscopy. Ann Intern Med. 2020;173:81–91. https://doi.org/10.7326/M19-2477.

    Article  PubMed  Google Scholar 

  55. Lam AY, Li Y, Gregory DL, Prinz J, O’Reilly J, Manka M, et al. Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program. Gastrointest Endosc. 2020;92:355–64 e355. https://doi.org/10.1016/j.gie.2020.02.016.

    Article  PubMed  Google Scholar 

  56. Castaneda D, Popov VB, Verheyen E, Wander P, Gross SA. New technologies improve adenoma detection rate, adenoma miss rate and polyp detection rate: a systematic review and meta-analysis. Gastrointest Endosc. 2018. https://doi.org/10.1016/j.gie.2018.03.022

    Article  PubMed  Google Scholar 

  57. Bogie RMM, Clercq CMC le, Voorham QJM, Cordes M, Sie D, Broek E vd, et al. OP212 Association of chromosomal instability and microsatellite instability pathways with postcolonoscopy colorectal cancer in a retrospective cohort study. United Eur Gastroenterol J. 2016;4(5_suppl):A1-A156 [Oral presentation 212].

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Acknowledgements

We thank the technicians of the pathology laboratory at the Netherlands Cancer Institute in Amsterdam for their help with the DNA isolations. We thank the Tumour Genome Analysis Core at Amsterdam UMC for low-coverage WGS and cancer-related gene panel-targeted sequencing. We thank the Genomics Core Facility at the Netherlands Cancer Institute for cancer-related gene panel-targeted sequencing. We thank the technicians of the pathology laboratory at the Maastricht University Medical Centre for their help with the CIMP analysis. We thank Dr. Silvia Sanduleanu for her contribution to the origin of this study. We acknowledge that a part of this work has been presented at the UEGW 2016 in Vienna [57]. This work was performed within the frame of the COST Action [CA17118], supported by COST (European Cooperation in Science and Technology).

Funding

RB and CLC received an unrestricted educational grant from Pentax Medical BV. BY contributed to the manuscript with the support of the Dutch Cancer Society (Grant No. KWF 2015-7882).

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

    Roel M. M. Bogie, Chantal M. C. le Clercq & Ad A. M. Masclee

  2. Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Quirinus J. M. Voorham, Christian Rausch, Evert van den Broek, Gerrit A. Meijer & Beatriz Carvalho

  3. Amsterdam UMC, location VUmc, Department of Pathology, Cancer Centre Amsterdam, Amsterdam, The Netherlands

    Martijn Cordes, Daoud Sie, Sara D. J. de Vries, Nicole C. T. van Grieken & Bauke Ylstra

  4. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

    Robert G. Riedl, Ernst-Jan Speel & Manon van Engeland

  5. Department of Pathology, Zuyderland Medical Centre, Heerlen, The Netherlands

    Robert G. Riedl & Prapto Sastrowijoto

  6. Department of Methodology and Statistics, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands

    Rein Vos & Bjorn Winkens

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  1. Roel M. M. Bogie
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Contributions

RB, CC, ME, GM and BC conceived the study concept and design; RB, CC, QV, MC, DS, CR, EB, SV, NG, RR, PS, ES, BY and BC contributed to the acquisition of the data; RB, CC, QV, MC, DS, CR, EB, SV, NG, RV, BW, ME, BY, GM, AM and BC participated in analysis and interpretation of the data; RB, CC, QV, CR, BW, AM and BC drafted the manuscript; all authors did a critical revision of the manuscript for important intellectual content; RB, CR, RV and BW performed the statistical analysis; AM and BC had the study supervision. AM is the guarantor of the article. All authors approved the final version.

Corresponding author

Correspondence to Ad A. M. Masclee.

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Competing interests

AM received funding from the Dutch Cancer Society, from the Dutch Organization for Health Research and Development, from Pentax Europe GmBH. AM has given scientific advice to Kyowa Kirin, Bayer, and Takeda. BC has several patents pending. The remaining authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Medical Ethical Committee of the Maastricht University Medical Centre, which waived the need for informed consent. The study is registered as study NTR3093 in the Dutch trial register (www.trialregister.nl). The study was performed in accordance with the Declaration of Helsinki.

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Bogie, R.M.M., le Clercq, C.M.C., Voorham, Q.J.M. et al. Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case–control study. Br J Cancer 126, 865–873 (2022). https://doi.org/10.1038/s41416-021-01619-z

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