title: Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States).
abstract: OBJECTIVE
  Insulin-like growth factor I (IGF-I) exerts potent mitogenic and antiapoptotic effects on prostatic epithelial cells. Insulin-like growth factor binding protein-3 (IGFBP-3) modulates the effects of IGF-I, and independently induces apoptosis and inhibits cell growth. Previous studies have inconsistently associated IGF-I and IGFBP-3 with prostate cancer. To try and further clarify these potential associations, we undertook a sibling-matched case-control study.
  
  
  METHODS
  Serum IGF-I and IGFBP-3 were determined for 845 men (408 cases and 437 sibling controls). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the serum IGF levels and prostate cancer.
  
  
  RESULTS
  Among all study subjects, only the molar ratio of IGF-I to IGFBP-3 was associated with prostate cancer: comparing those in the highest to lowest quartiles gave an OR = 1.62 (95% CI = 1.02-2.57, trend-p = 0.04). Among men with clinically less aggressive disease, we observed positive associations between prostate cancer and high levels of IGF-I (OR = 2.78, 95% CI = 1.06-6.80, trend-p = 0.03), and IGFBP-3 (OR = 2.68, 95% CI = 1.08-6.80, trend-p = 0.04). Simultaneously modeling both left the IGF-I result essentially unchanged, while substantially weakening the IGFBP-3 association.
  
  
  CONCLUSIONS
  We found that a high IGF-I to IGFBP-3 molar ratio was associated with an increased risk of prostate cancer. Furthermore, high IGF-I was associated with increased risk of prostate cancer among men with less advanced disease at diagnosis. These results lend support to the hypothesis that IGF-I, or the IGF-I to IGFBP-3 molar ratio, is an important risk factor for prostate cancer.
authors.affiliation: Department of Family Medicine, Case Western Reserve University, Cleveland, OH 44106-4945, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Fredrick
authors.initials: F
authors.lastname: Schumacher
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology*; D012307:Risk Factors; D014481:United States
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I