Carcinogenesis vol.29 no.7 pp.1360–1366, 2008 doi:10.1093/carcin/bgn083 Advance Access publication March 28, 2008
Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 1Genetic Epidemiology Group, and 2Epidemiology Methods and Support Group, International Agency for Research on Cancer, Lyon 69372, France, 3Department of Diet, Cancer and Health, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen 2100, Denmark, 4 Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg Aarhus 8000, Denmark, 5Department of Epidemiology and Public Health, Institut National de la Sante´ et de la Recherche Me´dicale, ERI 20, EA 4045 and Institut Gustave Roussy, Villejuif 94805, France, 6Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany, 7Department of Hygiene and Epidemiology, University of Athens Medical School, Athens 11527, Greece, 8Department of Epidemiology, Harvard School of Public Health, Boston MA 02115, USA, 9 Hellenic Health Foundation, Athens 11527, Greece, 10Molecular and Nutritional Epidemiology Unit, Center for Cancer Research and PreventionScientific Institute of Tuscany, Florence 50139, Italy, 11Nutritional Epidemiology Unit, National Cancer Institute, Milan 20133, Italy, 12Cancer Registry, Azienda Ospedaliera Civile M.P. Arezzo, Ragusa 97100, Italy, 13 Department of Epidemiology and Public Health, Imperial College, London SW7, UK, 14Public Health and Health Planning Directorate, Asturias Oviedo 33001, Spain, 15Laboratori de Recerca Translacional, Department of Epidemiology, Catalan Institute of Oncology, Barcelona (Institut d’Investigatio Biomedica de Bellvitge), L’Hospitalet de Llobregat, Barcelona 08907, Spain, 16 Andalusian School of Public Health, CIBER Epidemilogı´a y Salud Pu´blica, Granada 18011, Spain, 17Department of Public Health of Guipuzkoa, San Sebastian, Donostia-San Sebastian 20013, Spain, 18Department of Epidemiology, Murcia Health Council, CIBER en Epidemiologı´a y Salud Pu´blica (CIBERESP), Murcia Granada 18011, Spain, 19Public Health Institute of Navarra, CIBERESP, Pamplona 31003, Spain, 20Center for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven 3720 BA, The Netherlands, 21Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht 3508 GA, The Netherlands, 22 Department of Public Health and Clinical Medicine, Nutritional Research and, 23Department of Radiation Sciences, Oncology, Umea˚ University, Umea˚ 90187, Sweden, 24MRC Dunn Human Nutrition Unit, Cambridge CB2 0XY, UK, 25MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival Department of Public Health and Primary Care, University of Cambridge CB1 8RN, UK, 26Department of Public Health and Primary Care, University of Cambridge CB1 8RN, UK and 27Cancer Research UK, Epidemiology Unit, University of Oxford, Oxford OX3 7XP, UK
Abbreviations: BMI, body mass index; EPIC, European Prospective Investigation into Cancer and Nutrition; FPRP, false-positive report probability; GH, growth hormone; GHSR, growth hormone secretagogue receptor; IGFBP-3, insulin-like growth factor-binding protein 3; IGF-I, insulin growth factor I; SNP, single-nucleotide polymorphism.
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Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case–control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0–1.4; P 5 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P 5 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between
