Number of aberrant crypt foci associated with adiposity and IGF1 bioavailability

Abstract

Background Dysregulation of the insulin-like growth factor (IGF) system, a common consequence of adiposity-induced insulin resistance, may be a key underlying mechanism linking excess body weight with colon cancer. Evidence has been derived from studies of cancer and polyps. Supporting data about aberrant crypt foci (ACF), putative pre-polyp changes, have been generated only from animal studies to date. Methods We randomly selected 26 patients with sex-specific elevated waist-hip-ratio (WHR) and 26 with normal values from a series of 150 patients seeking routine colonoscopy at the University of Connecticut Health Center. Cross-sectional analyses were performed of ACF number (<5, ≥5) in relation to total IGF1, IGF-binding protein-3 (IGFBP3), insulin, body mass index (BMI), WHR and waist circumference (WC). Visualized ACF in the 20 cm of the distal colon were counted using advanced endoscopic imaging. Results Patients with ≥5 ACF had higher BMI, WHR, and WC compared with patients with >5 ACF (p = 0.04, p = 0.03, and p = 0.01, respectively). IGFBP3 was reduced (p = 0.02) and IGF1:IGFBP3 molar ratio was greater (p = 0.03) in patients with ≥5 ACF. We did not observe significant associations between ACF number and insulin or total IGF1. Conclusions Our study provides the first report in humans of a possible association of ACF prevalence and IGF1 bioavailability as characterized by IGF1:IGFBP3 molar ratio and IGFBP3 level. More research is needed to determine whether this relationship is varied by ACF features (e.g., size, dysplasia, molecular changes), synchronous cancer and polyps, and is modified by colon cancer risk factors.

One Year Recurrence of Aberrant Crypt Foci

“…Additionally, Swede et al showed increased BMI to be associated with increased number of prevalent ACF 4. Our result here, of a modest, but not statistically significantly elevated risk for recurrent ACF in obese subjects (OR=1.4) seems more in line with the literature than our earlier finding from the baseline exam.…”

Differential expression of TNF-α signaling molecules and ERK1 in distal and proximal colonic tumors associated with obesity

“…But there is considerable evidence that insulin and IGF-IR are important growth factors for gastrointestinal tissue and provide protection to several cell types, including colon cancer cells [21,22]. The presence of elevated insulin, IGF-IR, and TNF-α could act synergistically to provide superior survival and growth conditions to developing preneoplastic lesions and tumors [18,23,24]. Moreover, inhibition of NF-κB and MAPK is crucial for Bars not sharing a common superscript are significantly different, p<0.05, as determined by ANOVA analyses with LSD and Tukey post hoc tests reversing the survival signal mediated via IGF, as well as TNF-α [21].…”

Aberrant crypt foci as predictors of colorectal neoplasia on repeat colonoscopy

“…Subsequently these patients returned for a surveillance exam at UCHC for indications of a prior history of adenoma (n = 48) or family history of colon cancer (n = 26). The structure and methodology of the ACF Study have been described in detail elsewhere [9,10,13]. Briefly, the ACF Study is a clinic-based research program with a goal to characterize the clinical importance, epidemiologic risk factors for and molecular features of ACF and other early colonic neoplasia, which was approved by the UCHC Institutional Review Board.…”

“…Colon preparation prior to the procedure is performed with polyethylene glycolbased liquid as described in our prior reports [9,10]. ACF detection took place after the standard colonoscopy was completed.…”

“…A growing body of research has produced evidence of ACF as possible CRC precursors, but consensus has not yet been reached. Since their identification in post-mortem examinations in human studies [4,5], there have been studies which have demonstrated that risk factors for ACF include synchronous colorectal neoplasia, age, smoking, central obesity, markers of insulin resistance, and family history of CRC [6][7][8][9][10]. Their frequency may also correlate with advanced colorectal neoplasia in patients [7,8,11].…”