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Serum Concentrations of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein 3 and Recurrent Colorectal Adenomas

¹ Division of Epidemiology and Community Health, University of Minnesota and ² Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; ³ University of Florida, Gainesville, Florida; ⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute and ⁵ Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; ⁶ Information Management Services, Inc., Silver Spring, Maryland; and ⁷ Maine Center for Osteoporosis Research and Education, Bangor, Maine

Requests for reprints: Andrew Flood, Division of Epidemiology and Community Health, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454. Phone: 612-624-2891; Fax: 612-624-0315. E-mail: flood009{at}umn.edu

Insulin-like growth factor I (IGF-I) and its primary binding protein, IGFBP-3, have been associated with colorectal cancer incidence in prior epidemiologic studies. High concentrations of IGF-I generally result in increasing risk and high concentrations of IGFBP-3 in decreasing risk. Only one prior study of IGF-I and IGFBP-3 and adenoma recurrence has been reported. We assayed fasting serum from 375 subjects with and 375 subjects without a recurrent adenoma during the course of the Polyp Prevention Trial to determine baseline concentrations of IGF-I and IGFBP-3. To estimate relative risk of adenoma recurrence over the course of 4 years of follow-up for each of these serum measures, we calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression models adjusting for age, gender, body mass index, intervention group, aspirin, smoking, ethnicity, and education. For both IGF-I and IGFBP-3, we found trends indicating decreased risk for subjects in the high compared with the low quartile (for IGF-I: OR, 0.65; 95% CI 0.41-1.01; for IGFBP-3: OR, 0.66; 95% CI, 0.42-1.05). The associations were even greater for advanced adenomas (for IGF-I: OR, 0.51; 95% CI, 0.21-1.29; for IGFBP-3: OR, 0.32; 95% CI, 0.13-0.82). These results showed an unexpected null association, or even the suggestion of a reduction in risk for recurrent adenoma, with not just high IGFBP-3 concentration but also with high levels of IGF-I. Why IGF-I would decrease risk of recurrent adenoma (as distinct from incident adenoma or colorectal cancer) is not clear. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1493–8)