1. ¹International Agency for Research on Cancer, Lyon, France
2. ²Institut Gustave Roussy, Villejuif, France
3. ³German Cancer Research Centre, Heidelberg, Germany
4. ⁴German Institute of Human Nutrition, Potsdam, Germany
5. ⁵University of Athens Medical School, Athens, Greece
6. ⁶CSPO-Scientific Institute of Tuscany, Florence, Italy
7. ⁷Cancer Registry, Azienda Ospedaliera 'Civile MP Arezzo', Ragusa, Italy
8. ⁸Imperial College, London, UK
9. ⁹University of Torino, Turin, Italy
10. ¹⁰National Cancer Institute, Milan, Italy
11. ¹¹National Institute of Public Health and the Environment, Bilthoven, The Netherlands
12. ¹²Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
13. ¹³Catalan Institute of Oncology, Barcelona, Spain
14. ¹⁴Instituto de Salud Pública, SNS-O, Pamplona, Spain
15. ¹⁵Epidemiology Department, Murcia Health Council, Spain
16. ¹⁶Public Health Directorate, Consejería de Sanidad y Servicios Sociales de Asturias, Oviedo, Spain
17. ¹⁷Public Health Division of Gipuzkoa, Health Department of the Basque Country, San Sebastián, Spain
18. ¹⁸School of Public Health of Andalucia, Granada, Spain
19. ¹⁹Cancer Research UK, Epidemiology Unit, University of Oxford, Oxford, UK
20. ²⁰MRC Dunn Human Nutrition Unit, Welcome Trust/MRC Building, Cambridge, UK
21. ²¹Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK

Correspondence: Dr R Kaaks, Hormones and Cancer Team, International Agency for Research on Cancer, 150, cours Albert-Thomas, F-69372 Lyon, France. E-mail: kaaks@iarc.fr

Received 22 April 2005; Revised 17 November 2005; Accepted 21 November 2005; Published online 10 January 2006.

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.