title: Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer.
abstract: BACKGROUND
  Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.
  
  
  METHODS
  We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.
  
  
  RESULTS
  After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R(2) = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.
  
  
  CONCLUSIONS
  Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.
  
  
  CONCLUSIONS
  Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Fangyi
authors.initials: F
authors.lastname: Gu
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Demetrius
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authors.lastname: Albanes
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authors.initials: CD
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authors.lastname: Boeing
authors.forename: H Bas
authors.initials: HB
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authors.forename: Brian E
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authors.lastname: Henderson
authors.forename: David J
authors.initials: DJ
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authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.forename: Loic
authors.initials: L
authors.lastname: LeMarchand
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodriguez
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Shumin M
authors.initials: SM
authors.lastname: Zhang
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D017481:Receptors, Somatostatin; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; C094573:somatostatin receptor 5
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