• Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. Electronic address: neil.murphy@imperial.ac.uk.
• Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
• 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.
• Division of Epidemiology, Department of Environmental Medicine, NYU Langone Medical Center, NYU Cancer Institute, New York, NY, USA.

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.

CONCLUSION: 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.