title: A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women.
abstract: Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-I have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-I to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 3rd Floor, 181 Longwood Avenue, Boston, MA 02115, USA. esther.wei@channing.harvard.edu
authors.forename: Esther K
authors.initials: EK
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pollak
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D006946:Hyperinsulinism / Q000150:complications*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D002096:C-Peptide; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I