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Open Access Highly Accessed Research article

Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa

Adriana C Vidal1, Pauline Kay Lund23, Cathrine Hoyo1, Joseph Galanko2, Lauren Burcal2, Rachel Holston2, Berri Massa2, Oluwaseun Omofoye2, Robert S Sandler2 and Temitope O Keku2*

Author Affiliations

1 Department of Obstetrics and Gynecology, and Program of Cancer Detection, Prevention and Control, for Duke University School of Medicine, Durham, North Carolina

2 Department of Medicine and Center for Gastrointestinal Biology & Disease School of Medicine, University of North Carolina, Chapel Hill, North Carolina

3 Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina

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BMC Cancer 2012, 12:389  doi:10.1186/1471-2407-12-389

Published: 5 September 2012

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