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

• Main Authors: Vidal Adriana C, Lund Pauline, Hoyo Cathrine, Galanko Joseph, Burcal Lauren, Holston Rachel, Massa Berri, Omofoye Oluwaseun, Sandler Robert S, Keku Temitope O
• Format: Article
• Language: English
• Published: BMC 2012-09-01
• Series: BMC Cancer
• Subjects: Insulin; C-peptide; Insulin-like growth factor binding protein
• Online Access: http://www.biomedcentral.com/1471-2407/12/389

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 (>1^st 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).</p> <p>Conclusions</p> <p>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.</p>