This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wei, E. K. Articles by Giovannucci, E. Search for Related Content PubMed PubMed Citation Articles by Wei, E. K. Articles by Giovannucci, E.

C-Peptide, Insulin-like Growth Factor Binding Protein-1, Glycosylated Hemoglobin, and the Risk of Distal Colorectal Adenoma in Women

¹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of ² Epidemiology and ³ Nutrition, Harvard School of Public Health; ⁴ Department of Pathology, Harvard Medical School and the Department of Laboratory Medicine, Children's Hospital; ⁵ Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; and ⁶ Departments 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

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)

This article has been cited by other articles:

				E. T. Jacobs, M. E. Martinez, D. S. Alberts, E. L. Ashbeck, S. M. Gapstur, P. Lance, and P. A. Thompson Plasma Insulin-Like Growth Factor I Is Inversely Associated with Colorectal Adenoma Recurrence: A Novel Hypothesis Cancer Epidemiol. Biomarkers Prev., February 1, 2008; 17(2): 300 - 305. [Abstract] [Full Text] [PDF]

				R. Xiao, L. J Hennings, T. M Badger, and F. A Simmen Fetal programing of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone J. Endocrinol., October 1, 2007; 195(1): 79 - 87. [Abstract] [Full Text] [PDF]

				D. S. Michaud, B. Wolpin, E. Giovannucci, S. Liu, B. Cochrane, J. E. Manson, M. N. Pollak, J. Ma, and C. S. Fuchs Prediagnostic Plasma C-Peptide and Pancreatic Cancer Risk in Men and Women Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2101 - 2109. [Abstract] [Full Text] [PDF]

				E. Giovannucci Metabolic syndrome, hyperinsulinemia, and colon cancer: a review Am. J. Clinical Nutrition, September 1, 2007; 86(3): 836S - 842S. [Abstract] [Full Text] [PDF]