title: Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer.
abstract: BACKGROUND
  Adiponectin, an insulin-sensitizing adipokine, is inversely associated with adiposity and prostate cancer risk and progression. However, the role of genetic variation in the adiponectin (ADIPOQ) and receptor genes (ADIPOR1/R2) in prostate cancer is largely unknown.
  
  
  METHODS
  In a nested case-control study of 1,286 cases and 1,267 controls within the Physicians' Health Study, we evaluated 29 common single-nucleotide polymorphisms (SNP) in ADIPOQ (n = 13), ADIPOR1 (n = 5), and ADIPOR2 (n = 11) in relation to the risk of prostate cancer. In subgroups, we also evaluated the association of genotype and circulating adiponectin levels (n = 951) and prostate tumor expression of insulin receptor (IR) and insulin-like growth factor 1 (IGF-IR) receptor (n = 181).
  
  
  RESULTS
  Among the 12 tagging polymorphisms in ADIPOQ, four (rs266729, rs182052, rs822391, and rs2082940) were significantly associated (P < 0.05) with overall prostate cancer risk, with no significant difference by tumor grade or clinical stage. Two of the risk SNPs (rs266729 and rs182052) plus four other SNPs (rs16861209, rs17366568, rs3774261, and rs7639352) were also associated with plasma adiponectin levels, and three of these (rs1686109, rs17366568, and rs3774261) were also significantly associated with IR expression in prostate tumor tissue. One additional SNP was associated with IGFI-R tumor tissue expression (rs16861205). None of the 16 variants in ADIPOR1/R2 were related to cancer risk or circulating adiponectin levels.
  
  
  CONCLUSIONS
  Common variants in the adiponectin gene were associated with prostate cancer risk, plasma adiponectin levels, and IR or IGF-IR expression in the prostate tumor.
  
  
  CONCLUSIONS
  These genotype-phenotype associations support the biological relevance of adiponectin for prostate carcinogenesis, particularly in earlier stages of development.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School Boston, MA, USA.
authors.forename: Preet K
authors.initials: PK
authors.lastname: Dhillon
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.forename: Fredrick
authors.initials: F
authors.lastname: Schumacher
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Rider
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D054419:Receptors, Adiponectin / Q000235:genetics*; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin