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 nu

TitleGenetic 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 nu
Publication TypeJournal Article
Year of Publication2005
AuthorsCanzian, F, McKay, JD, Cleveland, RJ, Dossus, L, Biessy, C, Boillot, C, Rinaldi, S, Llewellyn, M, Chajès, V, Clavel-Chapelon, F, Tehard, B, Chang-Claude, J, Linseisen, J, Lahmann, PH, Pischon, T, Trichopoulos, D, Trichopoulou, A, Zilis, D, Palli, D, Tumino, R, Vineis, P, Berrino, F, H Bueno-de-Mesquita, B, van Gils, CH, Peeters, PHM, Pera, G, Barricarte, A, Chirlaque, M-D, J Quirós, R, Larrañaga, N, Martínez-García, C, Allen, NE, Key, TJ, Bingham, SA, Khaw, K-T, Slimani, N, Norat, T, Riboli, E, Kaaks, R
JournalCancer Epidemiol Biomarkers Prev
Volume14
Issue10
Pagination2316-25
Date Published2005 Oct
ISSN1055-9965
KeywordsAdult, Aged, Breast Neoplasms, Case-Control Studies, Europe, Female, Genotype, Growth Hormone, Growth Hormone-Releasing Hormone, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Male, Middle Aged, Polymorphism, Genetic, Pregnancy Proteins, Risk Factors
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.

DOI10.1158/1055-9965.EPI-04-0874
Alternate JournalCancer Epidemiol. Biomarkers Prev.
Citation Key10.1158/1055-9965.EPI-04-0874
PubMed ID16214911