title: Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa.
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 (>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).
  
  
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Vidal
authors.forename: Pauline Kay
authors.initials: PK
authors.lastname: Lund
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.forename: Joseph
authors.initials: J
authors.lastname: Galanko
authors.forename: Lauren
authors.initials: L
authors.lastname: Burcal
authors.forename: Rachel
authors.initials: R
authors.lastname: Holston
authors.forename: Berri
authors.initials: B
authors.lastname: Massa
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Omofoye
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015992:Body Mass Index; D002096:C-Peptide / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk
chemical_list: D002096:C-Peptide; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1