Insulin‐like Growth Factor (IGF)‐I, IGF‐binding Protein‐3 and Colorectal Adenomas in Japanese Men

Several epidemiological studies have found that high levels of plasma insulin‐like growth factor (IGF)‐I and low levels of IGF‐binding protein (IGFBP)‐3 are related to an increased risk of colorectal cancer or late‐stage adenomas. We examined the relation of body mass index, fasting and 2‐h postload plasma glucose levels and plasma concentrations of IGF‐I and IGFBP‐3 to colorectal adenomas in middle‐aged Japanese men. The study subjects comprised 157 cases of histologically diagnosed colorectal adenomas and 311 controls with normal colonoscopy or non‐polyp benign lesions in a consecutive series of 803 men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). After adjustment for rank in the SDF, hospital, smoking and IGFBP‐3, a statistically nonsignificant modest increase in the prevalence odds of colorectal adenomas was observed for the highest versus the lowest quartile level of IGF‐I. The increase was slightly greater with further adjustment for 2‐h glucose concentrations (adjusted odds ratio 1.8, 95% confidence interval 1.0–4.5, trend P=0.06). Men with high levels of IGFBP‐3 showed only a minimal decrease in risk after adjustment for IGF‐I. The association with IGF‐I was less evident for advanced adenomas (≥5 mm in size or tubulovillous/villous). Fasting and 2‐h glucose and body mass index were more strongly positively associated with colorectal adenomas than IGF‐I, especially with advanced adenomas, independently of IGF‐I and IGFBP‐3. The findings suggest that plasma IGF‐I and IGFBP‐3 may be involved in colorectal tumorigenesis regardless of the stage in growth of adenoma, but not as a mediator for the effects of being overweight or of hyperglycemia.