title: Serum insulin-like growth factors and mortality in localised and advanced clinically detected prostate cancer.
abstract: BACKGROUND
  Many studies have reported associations of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with prostate cancer development, but none have investigated their association with fatal progression of prostate cancer.
  
  
  OBJECTIVE
  We investigated associations of circulating IGF-I, IGF-II, IGFBP-2 and IGFBP-3 with all-cause and prostate cancer mortality in men with clinically identified prostate cancer, stratified by whether localised (stage T1 or T2) or advanced (T3, T4, N1 or M1) at diagnosis.
  
  
  METHODS
  UK hospital-based cohort study of 396 men with prostate cancer, diagnosed between 1990 and 2008, with mean follow-up of 3.7 years.
  
  
  METHODS
  All-cause and prostate cancer-specific mortality.
  
  
  RESULTS
  In men with advanced cancer, there was some evidence that IGF-I was positively associated (HR 1.20; 95% CI: 0.96, 1.49; p = 0.11) and IGFBP-3 was inversely associated (HR 0.84; 95% CI: 0.70, 1.01; p = 0.07) with all-cause mortality after controlling for age, treatment status, smoking, prostate-specific antigen and Gleason grade at diagnosis. There was some evidence that IGF-I was positively associated with prostate cancer mortality in advanced cases (HR 1.23; 95% CI: 0.94, 1.62; p = 0.13). In advanced cancers, associations of IGF-I with all-cause (HR 1.68; 95% CI: 1.28, 2.23; p < 0.001) and prostate cancer-specific (HR 1.59; 95% CI: 1.11, 2.28; p = 0.01) mortality strengthened (and were conventionally statistically significant) after further controlling for IGFBP-3.
  
  
  CONCLUSIONS
  Measures of IGF-I and IGFBP-3 may have potential as prognostic markers in predicting risk of death in men with advanced prostate cancer. Large, prospective studies with repeat IGFs and IGFBPs are now required.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.
authors.forename: Mari-Anne
authors.initials: MA
authors.lastname: Rowlands
authors.forename: Jeff M P
authors.initials: JM
authors.lastname: Holly
authors.forename: Freddie
authors.initials: F
authors.lastname: Hamdy
authors.forename: Joshua
authors.initials: J
authors.lastname: Phillips
authors.forename: Louise
authors.initials: L
authors.lastname: Goodwin
authors.forename: Gemma
authors.initials: G
authors.lastname: Marsden
authors.forename: David
authors.initials: D
authors.lastname: Gunnell
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000378:metabolism / Q000401:mortality*; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C035170:IGF2 protein, human; C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II