Association between factors associated with colorectal cancer and rectal aberrant crypt foci in humans

Aberrant crypt foci (ACF) are regarded as potential biomarkers for colorectal cancer (CRC), and have been used as such in recent early-phase chemoprevention trials. However, the associations between the presence of ACF and other factors associated with the development of CRC, such as lifestyle factors, medication use and comorbid medical conditions, remain unknown. Thus, the present retrospective, large, cross-sectional study was conducted to evaluate the potential usefulness of ACF as a surrogate biomarker of CRC. Total colonoscopy was performed and the number of rectal ACF was counted in a total of 902 subjects. A retrospective review of the medical records of the study subjects was performed, and the factors associated with the increased prevalence of ACF was investigated using univariate and multivariate logistic regression analyses. The analysis results identified older age [odds ratio (OR), 9.24; 95% confidence interval (CI), 4.80-17.8; P<0.01], smoking habit (OR, 1.78; 95% CI, 1.20-2.63; P<0.01) and use of insulin (OR, 9.97; 95% CI, 1.28-77.5; P=0.03) as significant independent risk factors associated with the increased prevalence of ACF, regardless of the presence/absence of colon tumors. In addition, it was revealed that the prevalence and number of ACF, and the Ki-67 labeling indices of the colonic epithelial cells were significantly higher in diabetic patients receiving insulin therapy than in those not receiving insulin therapy (P<0.01, P=0.03 and P=0.01, respectively). In conclusion, the potential usefulness of ACF as a surrogate biomarker of CRC was confirmed, although useful data could not be obtained on candidate chemopreventive agents. These results indicated that insulin can enhance colonic epithelial proliferative activity and induce the formation of ACF, thereby possibly triggering CRC development.