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Serum Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein-3 Concentrations and Prostate Cancer Risk: Results from the European Prospective Investigation into Cancer and Nutrition

¹ Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, United Kingdom; ² IARC, Lyon, France; ³ Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany; ⁴ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; ⁵ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; ⁶ Medical Department V, Aarhus University Hospital, Aarhus, Denmark; ⁷ Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark; ⁸ Departments of Epidemiology and Urology, University Medical Centre Nijmegen, Nijmegen, the Netherlands; ⁹ Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; ¹⁰ Medical Research Council Dunn Human Nutrition Unit and Medical Research Council Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge; ¹¹ Clinical Gerontology Unit, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom; ¹² Cancer Registry, Azienda Ospedaliera "Civile M.P. Arezzo," Ragusa, Italy; ¹³ Epidemiology Unit, Istituto Nazionale dei Tumori, Milan, Italy; ¹⁴ Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli Federico II, Naples, Italy; ¹⁵ Department of Biomedical Science and Human Oncology, Center for Cancer Prevention-Piemonte, Torino, Italy; ¹⁶ Molecular and Nutritional Epidemiology Unit, Center for Study and Prevention of Cancer, Scientific Institute of Tuscany, Florence, Italy; ¹⁷ Public Health and Health Planning Directorate, Asturias, Spain; ¹⁸ Public Health Institute of Navarra, Pamplona, Spain; ¹⁹ Department of Epidemiology, Murcia Health Council, Murcia, Spain; ²⁰ Public Health Department of Gipuzkoa, Basque Government, San Sebastian, Spain; ²¹ Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain; ²² Escuela Andaluza de Salud Publica, Granada, Spain; ²³ Department of Hygiene and Epidemiology, University of Athens Medical School; ²⁴ Hellenic Health Foundation, Athens, Greece; and ²⁵ Department of Epidemiology and Public Health, Imperial College, London, United Kingdom

Requests for reprints: Naomi E. Allen, Cancer Research UK Epidemiology Unit, University of Oxford, Oxford OX3 7LF, United Kingdom. Phone: 44-1865-289600; Fax: 44-1865-289610. E-mail: naomi.allen{at}ceu.ox.ac.uk

Background: Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer.

Methods: We analyzed the association between prediagnostic serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. This study includes 630 incident prostate cancer cases and 630 matched control subjects. Odds ratios and their 95% confidence intervals (95% CI) were calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3 concentrations using conditional logistic regression.

Results: The risk of total prostate cancer in the highest versus the lowest third of serum peptide concentration was 1.35 (95% CI, 0.99-1.82; P_trend = 0.08) for IGF-I, 1.39 (95% CI, 1.02-1.89; P_trend = 0.12) for the IGF-I residuals after adjusting for IGFBP-3, 1.22 (95% CI, 0.92-1.64; P_trend = 0.38) for IGFBP-3, and 1.01 (95% CI, 0.74-1.37; P_trend = 0.75) for the IGFBP-3 residuals after adjusting for IGF-I. There was no significant difference in the association of peptide hormones and prostate cancer by stage of disease, although the association of serum IGF-I concentration with risk was slightly stronger for advanced-stage disease; the odds ratio for the highest versus the lowest third was 1.65 (95% CI, 0.88-3.08; P_trend = 0.21) for IGF-I and 1.76 (95% CI, 0.92-3.40; P_trend = 0.11) for IGF-I adjusted for IGFBP-3.

Conclusions: In this large nested case-control study, serum IGF-I concentration is not strongly associated with prostate cancer risk, although the results are compatible with a small increase in risk, particularly for advanced-stage disease; no association for IGFBP-3 was observed. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1121–7)

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