title: Association between factors associated with colorectal cancer and rectal aberrant crypt foci in humans.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Yokohama Rosai Hospital, Yokohama, Kanagawa 222-0036, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ezuka
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sakai
authors.affiliation: Department of Gastroenterology, Yokohama Rosai Hospital, Yokohama, Kanagawa 222-0036, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kawana
authors.affiliation: Department of Gastroenterology, Yokohama Rosai Hospital, Yokohama, Kanagawa 222-0036, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagase
authors.affiliation: Department of Pathology, Yokohama Rosai Hospital, Yokohama, Kanagawa 222-0036, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kakuta
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohkubo
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Higurashi
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Endo
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan; Department of Gastroenterology, National Cancer Center, Tokyo 104-0045, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
keywords: Ki-67; aberrant crypt foci; colorectal cancer; colorectal carcinogenesis; insulin