title: Serum IGF1, IGF2 and IGFBP3 and risk of advanced colorectal adenoma.
abstract: The insulin-like growth factor (IGF) signaling pathway is involved in cell proliferation and differentiation. Elevated serum IGF1 levels have been associated with increased colorectal cancer risk; however, studies of this association with colorectal adenoma are inconclusive. We examined serum IGF1, IGF2 and IGFBP3 levels in relation to risk of advanced colorectal adenoma in a case-control study within the prostate, lung, colorectal and ovarian cancer screening trial. A total of 764 advanced, left-sided colorectal adenoma cases and 775 controls frequency-matched on gender and ethnicity, without evidence of a left-sided polyp on sigmoidoscopy were included in the current study. Serum levels of IGF1, IGF2 and IGFBP3 were measured using an enzyme linked immunosorbent assay in serum samples collected at baseline. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations adjusting for age, race, sex, year of blood draw, body mass index, smoking and education. Higher IGF1 levels were associated with increased adenoma risk: ORs = 1.58 (95% CI = 1.16-2.16), 1.42 (95% CI = 1.04-1.93), and 1.80 (95% CI = 1.30-2.47) for the second, third and fourth quartiles, respectively (p(trend)  = 0.002). Elevated IGF2 levels were also associated with increased adenoma risk (OR = 1.43, 95% CI = 1.05-1.96 for the fourth vs. first quartile, p(trend)  = 0.02), but the association was no longer significant after adjustment for IGF1 (p(trend)  = 0.28). IGFBP3 levels were not associated with adenoma risk. Our analysis showed a significant positive association between circulating IGF1 levels and risk of advanced colorectal adenoma, suggesting that IGF1 is associated with the pivotal precursor to colorectal cancer.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7236, USA. gaoying@mail.nih.gov
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Hormuzd
authors.initials: H
authors.lastname: Katki
authors.forename: Barry
authors.initials: B
authors.lastname: Graubard
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Tao
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.forename: Timothy
authors.initials: T
authors.lastname: Church
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
mesh_terms: D000236:Adenoma / Q000097:blood*; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; C035170:IGF2 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II