title: Genetic variation in the growth hormone synthesis pathway in relation to circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3, and breast cancer risk: results from the European prospective investigation into cancer and nutrition study.
abstract: Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk.
authors.affiliation: Hormones and Cancer Team, International Agency for Research on Cancer, 150 cours Albert-Thomas, F-69372 Lyon, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cleveland
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Carine
authors.initials: C
authors.lastname: Biessy
authors.forename: Catherine
authors.initials: C
authors.lastname: Boillot
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Midge
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authors.lastname: Llewellyn
authors.forename: Véronique
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authors.lastname: Chajès
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Bertrand
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authors.lastname: Téhard
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Petra H
authors.initials: PH
authors.lastname: Lahmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Dimosthenes
authors.initials: D
authors.lastname: Zilis
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Guillem
authors.initials: G
authors.lastname: Pera
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: J Ramon
authors.initials: JR
authors.lastname: Quirós
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez-García
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Teresa
authors.initials: T
authors.lastname: Norat
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005838:Genotype; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011257:Pregnancy Proteins / Q000097:blood*; D012307:Risk Factors
chemical_list: C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011257:Pregnancy Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone