C-Peptide, Insulin-like Growth Factor Binding Protein-1, Glycosylated Hemoglobin, and the Risk of Distal Colorectal Adenoma in Women
- Esther K. Wei1,2,
- Jing Ma1,
- Michael N. Pollak6,
- Nader Rifai4,
- Charles S. Fuchs1,5,
- Susan E. Hankinson1,2 and
- Edward Giovannucci1,2,3
- 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of 2Epidemiology and 3Nutrition, Harvard School of Public Health; 4Department of Pathology, Harvard Medical School and the Department of Laboratory Medicine, Children's Hospital; 5Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; and 6Departments of Medicine and Oncology, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Quebec, Canada
- Requests for reprints:
Esther K. Wei, Channing Laboratory, 181 Longwood Avenue, 3rd Floor, Boston, MA 02115. Phone: 617-525-0083; Fax: 617-525-2008. E-mail: esther.wei{at}channing.harvard.edu
Abstract
Background: Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer.
Methods: We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases and controls were individually matched on year of birth, time period of and indication(s) for endoscopy, and date of blood draw.
Results: High concentrations of C-peptide, an indicator of insulin secretion, were statistically significantly associated with risk of distal colorectal adenoma [multivariable relative risk (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01-2.66; P = 0.01], even after including body mass index and physical activity in the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did not show any clear association with risk for adenoma (MVRR top versus bottom quartile, 1.08; 95% CI, 0.56-2.07). These associations did not differ significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was associated with a nonstatistically significant increased risk of colorectal adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44).
Conclusions: High HbA1c and low IGFBP-1 were not clearly associated with increased risk of distal colorectal adenoma. However, our current results and previous associations between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a role throughout the development of colorectal neoplasia. (Cancer Epidemiol Biomarkers Prev 2006;15(4):750–5)
Footnotes
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Grant support: USPHS grants CA87969, CA49449, CA90598, CA42182 and T32 CA 09001 from the National Cancer Institute, NIH, Department of Health and Human Services.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted February 7, 2006.
- Received October 19, 2005.
- Revision received January 18, 2006.
