title: Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the breast and prostate cancer cohort consortium (BPC3).
abstract: BACKGROUND
  Sex steroids play a central role in breast cancer development.
  
  
  OBJECTIVE
  This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG.
  
  
  METHODS
  Data on 700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC).
  
  
  METHODS
  We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC.
  
  
  METHODS
  Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk.
  
  
  RESULTS
  Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk.
  
  
  CONCLUSIONS
  We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Beckmann
authors.forename: A
authors.initials: A
authors.lastname: Hüsing
authors.forename: V W
authors.initials: VW
authors.lastname: Setiawan
authors.forename: P
authors.initials: P
authors.lastname: Amiano
authors.forename: F
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: S J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: D G
authors.initials: DG
authors.lastname: Cox
authors.forename: R
authors.initials: R
authors.lastname: Diver
authors.forename: L
authors.initials: L
authors.lastname: Dossus
authors.forename: H S
authors.initials: HS
authors.lastname: Feigelson
authors.forename: C
authors.initials: C
authors.lastname: Haiman
authors.forename: G
authors.initials: G
authors.lastname: Hallmans
authors.forename: R B
authors.initials: RB
authors.lastname: Hayes
authors.forename: B E
authors.initials: BE
authors.lastname: Henderson
authors.forename: R N
authors.initials: RN
authors.lastname: Hoover
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: K
authors.initials: K
authors.lastname: Khaw
authors.forename: L N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: P
authors.initials: P
authors.lastname: Kraft
authors.forename: E
authors.initials: E
authors.lastname: Lund
authors.forename: L
authors.initials: L
authors.lastname: Le Marchand
authors.forename: P H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: E
authors.initials: E
authors.lastname: Riboli
authors.forename: D
authors.initials: D
authors.lastname: Stram
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: M J
authors.initials: MJ
authors.lastname: Thun
authors.forename: R
authors.initials: R
authors.lastname: Tumino
authors.forename: D
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: U
authors.initials: U
authors.lastname: Vogel
authors.forename: W C
authors.initials: WC
authors.lastname: Willett
authors.forename: M
authors.initials: M
authors.lastname: Yeager
authors.forename: R
authors.initials: R
authors.lastname: Ziegler
authors.forename: S E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: R
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D005006:Ethnicity; D005060:Europe / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D012739:Gonadal Steroid Hormones / Q000235:genetics / Q000378:metabolism; D006728:Hormones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism*; D018570:Risk Assessment; D013256:Steroids / Q000378:metabolism*
chemical_list: D012739:Gonadal Steroid Hormones; D006728:Hormones; D013256:Steroids