title: Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
abstract: BACKGROUND
  Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3).
  
  
  METHODS
  We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects.
  
  
  RESULTS
  Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels.
  
  
  CONCLUSIONS
  Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany. f.canzian@dkfz.de
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Henderson
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Christine
authors.initials: C
authors.lastname: Berg
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Julie
authors.initials: J
authors.lastname: Buring
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Francoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Robert
authors.initials: R
authors.lastname: Hoover
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Per
authors.initials: P
authors.lastname: Lenner
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Celeste Leigh
authors.initials: CL
authors.lastname: Pearce
authors.forename: Jose R
authors.initials: JR
authors.lastname: Quiros
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
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: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005091:Exons; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D009361:Neoplasm Invasiveness; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011498:Protein Precursors / Q000235:genetics*; D011966:Receptors, LHRH / Q000235:genetics*; D044465:White People
chemical_list: C484844:GNRHR protein, human; D011498:Protein Precursors; D011966:Receptors, LHRH; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone