Associations of Plasma C-Peptide and IGFBP-1 Levels with Risk of Colorectal Adenoma in a Multiethnic Population

Abstract

Circulating levels of insulin and insulin-like growth factor (IGF) hormones have been associated with colorectal cancer risk, but few studies have examined their associations with colorectal adenoma. We measured plasma C-peptide, a marker of insulin secretion, and IGF hormones in a case-control study of 554 pathologically confirmed, first-time adenoma cases and 786 controls with normal endoscopy among Caucasians, Japanese, and Native Hawaiians in Hawaii. High plasma levels of C-peptide were statistically significantly associated with risk of colorectal adenoma [multivariate odds ratio (95% confidence interval) for increasing quartiles: 1.0, 0.91 (0.65-1.27), 1.21 (0.86-1.71), and 1.79 (1.23-2.60); P(trend) = 0.0002]. We also observed a statistically significant inverse association between levels of plasma IGF binding protein-1 (IGFBP-1) and adenoma risk [1.0, 0.97 (0.70-1.34), 0.82 (0.58-1.15), and 0.47 (0.32-0.70); P(trend) <0.0001]. These associations remain significant after adjusting for each other and were not confounded by known risk factors. IGF-I, IGFBP-3, body mass index, and waist or hip circumference were not independently associated with adenoma risk. These results provide evidence for an association of insulin and IGFBP-1 levels with colorectal adenoma. This study suggests that hyperinsulinemia and IGF hormones may act as etiologic factors in colorectal carcinogenesis, as early as during adenoma formation.