title: Serum insulin-like growth factor I (IGF-I), IGF-binding proteins 2 and 3, and the risk for development of malignancies in adults with growth hormone (GH) deficiency treated with GH: data from KIMS (Pfizer International Metabolic Database).
abstract: BACKGROUND
  The association between IGFs and cancer in adults with GH deficiency (GHD) receiving GH replacement requires investigation.
  
  
  OBJECTIVE
  The objective was to examine the association between IGF-I, IGF-binding protein 2 (IGFBP-2), and IGFBP-3 SD scores (SDSs) in GH-deficient adults receiving GH therapy and the occurrence of de novo malignancies.
  
  
  METHODS
  Serum IGF-I, IGFBP-2, and IGFBP-3 levels in GH-deficient patients who developed a malignancy since receiving GH were compared with patients with idiopathic GHD but without malignancy. Measurements were related to age-, sex-, and body mass index-specific SDS reference regions.
  
  
  METHODS
  The setting included the KIMS (the Pfizer International Metabolic Database).
  
  
  METHODS
  One hundred patients with de novo malignancy during GH therapy were compared with 325 patients with idiopathic GHD without malignancy.
  
  
  METHODS
  Serum samples were obtained as close as possible to the diagnosis of malignancy, or after approximately 2 yr of GH replacement in KIMS.
  
  
  METHODS
  Associations between relative risk (RR) of malignancy and IGF-I, IGFBP-2, and IGFBP-3 SDSs were assessed in multiple log-linear Poisson working regression models, controlling for age, sex, onset of GHD, and GH naivety at KIMS entry.
  
  
  RESULTS
  No association between IGF-I SDSs and RR was observed (P = 0.48). Increasing IGFBP-2 and IGFBP-3 SDSs were associated with increasing RRs [18% per unit IGFBP-2 SDSs (95% confidence interval, 7-30%; P = 0.0006), 13% per unit IGFBP-3 SDS (2-26%; P = 0.01)].
  
  
  CONCLUSIONS
  IGF-I levels targeted to within normal age-related reference ranges during GH replacement were not associated with the occurrence of malignancies. Higher IGFBP-2 and/or IGFBP-3 SDSs may be associated with increased cancer risk.
authors.affiliation: Neuroendocrine Unit, Endocrinology Clinic, University Clinical Center, Dr. Subotic 13, 11000 Belgrade, Serbia. popver@Eunet.rs.
authors.forename: Vera
authors.initials: V
authors.lastname: Popovic
authors.forename: Anders F
authors.initials: AF
authors.lastname: Mattsson
authors.forename: Rolf C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: Patrick
authors.initials: P
authors.lastname: Wilton
authors.forename: Maria
authors.initials: M
authors.lastname: Koltowska-Häggström
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ranke
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016208:Databases, Factual; D004345:Drug Industry; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D012306:Risk
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I