Number of aberrant crypt foci associated with adiposity and IGF1 bioavailability.
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, > or = 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 > or = 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 > or = 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.
Swede
Helen
H
Colon Cancer Prevention Program, Neag Comprehensive Cancer Center, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-6325, USA. hswede@uchc.edu
Rohan
Thomas E
TE
Yu
Herbert
H
Anderson
Joseph C
JC
Stevens
Richard G
RG
Brokaw
Jane
J
Levine
Joel
J
Brenner
Bruce M
BM
Malchoff
Carl D
CD
Duffy
Valerie B
VB
Pleau
Devon C
DC
Rosenberg
Daniel W
DW
D050154:Adiposity / Q000502:physiology*; D000328:Adult; D015992:Body Mass Index; D003110:Colonic Neoplasms / Q000473:pathology; D003111:Colonic Polyps / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D055105:Waist Circumference; D049629:Waist-Hip Ratio
D007334:Insulin-Like Growth Factor I