Serum Concentrations of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein 3 and Recurrent Colorectal Adenomas
- Andrew Flood1,2,
- Volker Mai3,
- Ruth Pfeiffer4,
- Lisa Kahle6,
- Clifford J. Rosen7,
- Elaine Lanza5 and
- Arthur Schatzkin4
- 1Division of Epidemiology and Community Health, University of Minnesota and 2Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; 3University of Florida, Gainesville, Florida; 4Division of Cancer Epidemiology and Genetics, National Cancer Institute and 5Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; 6Information Management Services, Inc., Silver Spring, Maryland; and 7Maine 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
Abstract
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)
Footnotes
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Grant support: NIH K07 CA108910-01A1 (A. Flood) and Intramural Research Program funds from the National Cancer Institute, Bethesda, MD.
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Contributions of Authors: Andrew Flood and Volker Mai designed the study elements related to serum concentrations of insulin, glucose, IGF-I, and IGFBP-3. Andrew Flood also analyzed the data and drafted the manuscript. Volker Mai also assisted in the preparation of the manuscript. Ruth Pfeiffer provided statistical expertise and assisted in drafting the manuscript. Lisa Kahle provided statistical programming support and assisted in preparation of the manuscript. Clifford Rosen did the IGF-I and IGFBP-3 assays and assisted in the preparation of the manuscript. Elaine Lanza and Arthur Schatzkin designed and directed the overall Polyp Prevention Study; assisted in the design of the study elements related to serum insulin, glucose, IGF-I, and IGFBP-3; and assisted in preparing the manuscript.
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- Accepted April 8, 2008.
- Received January 16, 2008.
- Revision received March 7, 2008.
