Insulin-Like Growth Factor-I and Insulin Are Associated With the Presence and Advancement of Adenomatous Polyps

Background & Aims: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer. Methods: Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements. Results: Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0–2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1–3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2–3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3–6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0–5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1–4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk. Conclusions: Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.

Abbreviations used in this paper:  CRC, colorectal cancer, IGF-I, insulin like growth factor-I, IGFBP-3, insulin-like growth factor binding protein-3, VAT, visceral adipose tissue