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BMC Cancer. 2012; 12: 389.
Published online 2012 September 5. doi:  10.1186/1471-2407-12-389
PMCID: PMC3489909
Copyright ©2012 Vidal et al.; licensee BioMed Central Ltd.
Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa
Adriana C Vidal,1 Pauline Kay Lund,2,3 Cathrine Hoyo,1 Joseph Galanko,2 Lauren Burcal,2 Rachel Holston,2 Berri Massa,2 Oluwaseun Omofoye,2 Robert S Sandler,2 and Temitope O Kekucorresponding author2
1Department of Obstetrics and Gynecology, and Program of Cancer Detection, Prevention and Control, for Duke University School of Medicine, Durham, North Carolina
2Department of Medicine and Center for Gastrointestinal Biology & Disease School of Medicine, University of North Carolina, Chapel Hill, North Carolina
3Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina
corresponding authorCorresponding author.
Adriana C Vidal: adriana.vidal/at/duke.edu; Pauline Kay Lund: empk/at/med.unc.edu; Cathrine Hoyo: cathrine.hoyo/at/duke.edu; Joseph Galanko: galanko/at/med.unc.edu; Lauren Burcal: burcal/at/email.unc.edu; Rachel Holston: holstonr/at/email.unc.edu; Berri Massa: berri_massa/at/email.unc.edu; Oluwaseun Omofoye: oluwaseun_omofoye/at/med.unc.edu; Robert S Sandler: rsandler/at/med.unc.edu; Temitope O Keku: tokeku/at/med.unc.edu
Received April 26, 2012; Accepted August 31, 2012.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Lower concentrations of the insulin–like growth factor binding protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been associated with an increase in colorectal cancer risk (CRC). However few studies have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only known precursor for CRC.
Methods
Between November 2001 and December 2002, we examined associations between circulating concentrations of insulin, C-peptide, IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps and 488 with no adenomatous polyps using logistic regression models.
Results
Individuals with the highest concentrations of C-peptide were more likely to have adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations; associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than women. Individuals with high insulin concentrations also had a higher risk of adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1-0.7). Overweight and obese individuals with higher C-peptide levels (>1st Q) were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an association that remained strong in overweight and obese men (OR = 6.3, 95% CI 1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0).
Conclusions
Associations between these peptides and the apoptosis index in overweight and obese individuals, suggest that the mechanism by which C-peptide could induce adenomas may include its anti-apoptotic properties. This study suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that outcomes associated with colorectal carcinogenesis maybe modified by gender.
Keywords: Insulin, C-peptide, Insulin-like growth factor binding protein
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