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

Federico Canzian, James D. McKay, Rebecca J. Cleveland, Laure Dossus, Carine Biessy, Catherine Boillot, Sabina Rinaldi, Midge Llewellyn, Véronique Chajès, Françoise Clavel-Chapelon, Bertrand Téhard, Jenny Chang-Claude, Jakob Linseisen, Petra H. Lahmann, Tobias Pischon, Dimitrios Trichopoulos, Antonia Trichopoulou, Dimosthenes Zilis, Domenico Palli, Rosario TuminoPaolo Vineis, Franco Berrino, H. Bas Bueno-De-Mesquita, Carla H. Van Gils, Petra H M Peeters, Guillem Pera, Aurelio Barricarte, Maria Dolores Chirlaque, J. Ramon Quiros, Nerea Larrañaga, Carmen Martínez-García, Naomi E. Allen, Timothy J. Key, Sheila A. Bingham, Kay Tee Khaw, Nadia Slimani, Teresa Norat, Elio Riboli, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2316-2325
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 2005

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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