A prospective evaluation of C-peptide levels and colorectal adenoma incidence

•Higher insulin levels have been associated with greater colorectal cancer risk.•Whether insulin is similarly related to colorectal adenomas (colorectal cancer precursors) is unclear.•We prospectively examined the relationship between C-peptide levels (a marker of insulin) and colorectal adenoma.•No relationship between C-peptide and colorectal adenoma was observed.•Our results suggest that non-insulin related molecular pathways may be more relevant to early stages of colorectal tumorigenesis.

BackgroundObesity 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.MethodsIn 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.ResultsIn 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.ConclusionOur 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.