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

Item Type:	Article
Title:	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
Creators Name:	Canzian, F. and McKay, J.D. and Cleveland, R.J. and Dossus, L. and Biessy, C. and Rinaldi, S. and Landi, S. and Boillot, C. and Monnier, S. and Chajes, V. and Clavel-Chapelon, F. and Tehard, B. and Chang-Claude, J. and Linseisen, J. and Lahmann, P.H. and Pischon, T. and Trichopoulos, D. and Trichopoulou, A. and Zilis, D. and Palli, D. and Tumino, R. and Vineis, P. and Berrino, F. and Bueno-de-Mesquita, H.B. and van Gils, C.H. and Peeters, P.H. and Pera, G. and Ardanaz, E. and Chirlaque, M.D. and Quiros, J.R. and Larrañaga, N. and Martínez-García, C. and Allen, N.E. and Key, T.J. and Bingham, S.A. and Khaw, K.T. and Slimani, N. and Norat, T. and Riboli, E. and Kaaks, R.
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.
Keywords:	IGF-I, IGFBP-3, IGFBP-1, IGFALS, Single Nucleotide Polymorphisms, Breast Cancer
Source:	British Journal of Cancer
ISSN:	0007-0920
Publisher:	Nature Publishing Group
Volume:	94
Number:	2
Page Range:	299-307
Date:	24 January 2006
Official Publication:	https://doi.org/10.1038/sj.bjc.6602936
PubMed:	View item in PubMed

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