title: Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.
abstract: There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P(trend) = 1.5 × 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: V Wendy
authors.initials: VW
authors.lastname: Setiawan
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Lars
authors.initials: L
authors.lastname: Beckmann
authors.forename: Hélène
authors.initials: H
authors.lastname: Blanché
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Julie
authors.initials: J
authors.lastname: Buring
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Buys
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: John Oliver L
authors.initials: JO
authors.lastname: DeLancey
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
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: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D012739:Gonadal Steroid Hormones / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054547:National Cancer Institute (U.S.); D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D011786:Quality Control; D012307:Risk Factors; D014481:United States
chemical_list: D012739:Gonadal Steroid Hormones; D007334:Insulin-Like Growth Factor I