title: Interactions between genome-wide significant genetic variants and circulating concentrations of insulin-like growth factor 1, sex hormones, and binding proteins in relation to prostate cancer risk in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
abstract: Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. kostas.tsilidis@ceu.ox.ac.uk
authors.forename: Konstantinos K
authors.initials: KK
authors.lastname: Tsilidis
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Paul N
authors.initials: PN
authors.lastname: Appleby
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Sara
authors.initials: S
authors.lastname: Lindstrom
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: David
authors.initials: D
authors.lastname: Cox
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Afshan
authors.initials: A
authors.lastname: Siddiq
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: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D055106:Genome-Wide Association Study; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D012738:Sex Hormone-Binding Globulin; D007334:Insulin-Like Growth Factor I