title: Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis.
abstract: BACKGROUND
  Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk.
  
  
  METHODS
  We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale.
  
  
  RESULTS
  We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies.
  
  
  CONCLUSIONS
  Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.
authors.affiliation: Department of Surgery, Christie Hospital NHS Trust, Manchester, UK. arenehan@picr.man.ac.uk
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Renehan
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.forename: Christoph
authors.initials: C
authors.lastname: Minder
authors.forename: Sarah T
authors.initials: ST
authors.lastname: O'Dwyer
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shalet
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D001943:Breast Neoplasms / Q000097:blood; 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*; D008175:Lung Neoplasms / Q000097:blood; D008297:Male; D008593:Menopause; D009369:Neoplasms / Q000097:blood* / Q000209:etiology; D017697:Premenopause; D011471:Prostatic Neoplasms / Q000097:blood; D012307:Risk Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I