Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.

TitlePolymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.
Publication TypeJournal Article
Year of Publication2006
AuthorsCanzian, F, McKay, JD, Cleveland, RJ, Dossus, L, Biessy, C, Rinaldi, S, Landi, S, Boillot, C, Monnier, S, Chajès, V, Clavel-Chapelon, F, Téhard, B, Chang-Claude, J, Linseisen, J, Lahmann, PH, Pischon, T, Trichopoulos, D, Trichopoulou, A, Zilis, D, Palli, D, Tumino, R, Vineis, P, Berrino, F, Bueno-de-Mesquita, HB, van Gils, CH, Peeters, PHM, Pera, G, Ardanaz, E, Chirlaque, M-D, Quiros, JR, Larrañaga, N, Martínez-Garcia, C, Allen, NE, Key, TJ, Bingham, SA, Khaw, K-T, Slimani, N, Norat, T, Riboli, E, Kaaks, R
JournalBr J Cancer
Volume94
Issue2
Pagination299-307
Date Published2006 Jan 30
ISSN0007-0920
KeywordsAdult, Aged, Breast Neoplasms, Case-Control Studies, Female, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors
Abstract

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

DOI10.1038/sj.bjc.6602936
Alternate JournalBr. J. Cancer
Citation Key10.1038/sj.bjc.6602936
PubMed ID16404426
PubMed Central IDPMC2361124
Grant ListG0401527 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom