title: C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, and the risk of distal colorectal adenoma in women.
abstract: BACKGROUND
  Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer.
  
  
  METHODS
  We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases and controls were individually matched on year of birth, time period of and indication(s) for endoscopy, and date of blood draw.
  
  
  RESULTS
  High concentrations of C-peptide, an indicator of insulin secretion, were statistically significantly associated with risk of distal colorectal adenoma [multivariable relative risk (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01-2.66; P = 0.01], even after including body mass index and physical activity in the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did not show any clear association with risk for adenoma (MVRR top versus bottom quartile, 1.08; 95% CI, 0.56-2.07). These associations did not differ significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was associated with a nonstatistically significant increased risk of colorectal adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44).
  
  
  CONCLUSIONS
  High HbA1c and low IGFBP-1 were not clearly associated with increased risk of distal colorectal adenoma. However, our current results and previous associations between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a role throughout the development of colorectal neoplasia.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. esther.wei@channing.harvard.edu
authors.forename: Esther K
authors.initials: EK
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pollak
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
mesh_terms: D000236:Adenoma / Q000097:blood / Q000209:etiology*; D000328:Adult; D002096:C-Peptide / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000209:etiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk
chemical_list: D002096:C-Peptide; D006442:Glycated Hemoglobin; D018970:Insulin-Like Growth Factor Binding Protein 1