Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case-control study

Monique M. Gerrits*, Wei-Min Chen, Myrte J G A Theeuwes, Herman van Dekken, Marjolein Sikkema, Ewout W. Steyerberg, Hester F. Lingsma, Peter D. Siersema, Bing Xia, Johannes G. Kusters, C. Janneke van der Woude, Ernst J. Kuipers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Web of Science)

Abstract

Background Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy. Methods A case-control study was performed to determine the prognostic value of DNA ploidy and p53 in IBD-related neoplasia. Cases with IBD-related colorectal cancer (CRC), detected in our surveillance program between 1985-2008, were selected and matched with two controls, for age, gender, disease characteristics, interval of follow-up, PSC, and previous surgery. Biopsies were assessed for DNA ploidy, p53, grade of inflammation and neoplasia. Progression to neoplasia was analyzed with Cox regression analysis, adjusting for potentially confounding variables. Results Adjusting for age, we found statistically significant Hazard ratios (HR) between development of CRC, and low grade dysplasia (HR5.5; 95% CI 2.6-11.5), abnormal DNA ploidy (DNA index (DI) 1.06-1.34, HR4.7; 95% CI 2.9-7.8 and DI>1.34, HR6.6; 95% CI 3.7-11.7) and p53 immunopositivity (HR3.0; 95% CI 1.9-4.7) over time. When adjusting for all confounders, abnormal DNA ploidy (DI 1.06-1.34, HR4.7; 95% CI 2.7-7.9 and DI>1.34, HR5.0; 95% CI 2.5-10.0) and p53 immunopositivity (HR1.7; 95% CI 1.0-3.1) remained statistically significant predictive of neoplasia. Conclusion In longstanding IBD, abnormal DNA ploidy and p53 immunopositivity are important risk factors of developing CRC. The yield of surveillance may potentially increase by adding these biomarkers to the routine assessment of biopsies.
Original languageEnglish
Pages (from-to)107-117
JournalCellular oncology
Volume34
Issue number2
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Inflammatory bowel disease
  • Colorectal cancer
  • Surveillance
  • Abnormal DNA ploidy
  • p53 immunopositivity

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