title: A prospective evaluation of C-peptide levels and colorectal adenoma incidence.
abstract: BACKGROUND
  Obesity is a recognised positive risk factor for colorectal adenoma and colorectal cancer. Obesity is associated with insulin resistance and compensatory hyperinsulinaemia, and circulating insulin and C-peptide, a biomarker of insulin levels, have been positively associated with colorectal cancer risk. However, whether a similar relationship exists for colorectal adenomas, an established colorectal cancer precursor, is unclear.
  
  
  METHODS
  In a nested case-control study of 273 colorectal adenoma cases and 355 matched controls from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, serum C-peptide levels were measured by a chemiluminescent immunometric assay. Multivariable unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for colorectal adenoma within quartiles of C-peptide. Further, to explore the temporal stability of C-peptide, repeat samples from the incident adenoma cases (n=50) and controls (n=30), over a 5-year period were assayed and the intra-class correlations (ICC) estimated.
  
  
  RESULTS
  In a multivariable model that included established colorectal adenoma risk factors, C-peptide levels were not associated with colorectal adenoma (Q4 vs. Q1, OR 0.83, 95% CI: 0.52-1.31; P-trend 0.32); similar null associations were observed by gender, by adenoma subsite and for advanced adenomas. Among control participants, the ICC value over a 5-year period was 0.66.
  
  
  CONCLUSIONS
  Our results suggest that higher C-peptide levels were not associated with colorectal adenoma incidence in this study population. Other biological pathways associated with obesity may be more relevant to the early stages of colorectal tumorigenesis.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. Electronic address: neil.murphy@imperial.ac.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Murphy
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: Vian
authors.initials: V
authors.lastname: Rajabzadeh-Heshejin
authors.affiliation: Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Stanczyk
authors.affiliation: Division of Epidemiology, Department of Environmental Medicine, NYU Langone Medical Center, NYU Cancer Institute, New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Hayes
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
mesh_terms: D000236:Adenoma / Q000175:diagnosis*; D002096:C-Peptide / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D002096:C-Peptide
keywords: Adenoma; C-peptide, Hyperinsulinaemia; Cancer; Colorectal; Insulin; Resistance