TY - JOUR
T1 - Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case-control study
AU - Gerrits, Monique M.
AU - Chen, Wei-Min
AU - Theeuwes, Myrte J G A
AU - van Dekken, Herman
AU - Sikkema, Marjolein
AU - Steyerberg, Ewout W.
AU - Lingsma, Hester F.
AU - Siersema, Peter D.
AU - Xia, Bing
AU - Kusters, Johannes G.
AU - van der Woude, C. Janneke
AU - Kuipers, Ernst J.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
KW - Inflammatory bowel disease
KW - Colorectal cancer
KW - Surveillance
KW - Abnormal DNA ploidy
KW - p53 immunopositivity
U2 - 10.1007/s13402-010-0006-4
DO - 10.1007/s13402-010-0006-4
M3 - Article
C2 - 21327897
SN - 2211-3428
VL - 34
SP - 107
EP - 117
JO - Cellular oncology
JF - Cellular oncology
IS - 2
ER -