Serum IGF-I & Epithelial Ovarian Cancer Risk: Under 55

Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)

Petra H M Peeters, Annekatrin Lukanova1, Naomi Allen2, Franco Berrino3, Tim Key2, Laure Dossus4, Sabina Rinaldi4, Carla H van Gils, H Bas Bueno-de-Mesquita5, Heiner Boeing6, Mandy Schulz6, Jenny Chang-Claude7, Jakob Linseisen7, Salvatore Panico8, Carlotta Sacerdote9, Domenico Palli10, Rosario Tumino11, Antonia Trichopoulou12, Dimitrios Trichopolos12, Christina Bamia12, Nerea Larranaga13, Eva Ardanaz14, Guillem Pera15, J Ramón Quirós16, Carmen Martínez-García17, Carmen Navarro18, Sheila A Bingham19, Kay-Tee Khaw20, Françoise Clavel21, Anne Tjonneland22, Anja Olsen22, Kim Overvad23, Mette S Tetsche23, Eiliv Lund24, Eva Lundin25, Göran Berglund26, Elio Riboli27 and R Kaaks4

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands 1 Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA 2 Epidemiology Unit, Cancer Research UK, University of Oxford, Richard Doll Building, Oxford, UK 3 National Cancer Institute, Milan, Italy 4 IARC International Agency for Research on Cancer (IARC-WHO), Lyon, France 5 Center for Nutrition and Health, National Institute of Public Health and the Environment, Bilthoven, The Netherlands 6 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrucke, Germany 7 Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany 8 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy 9 CPO-Piemonte, Torino, Italy 10 Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy 11 Cancer Registry, Azienda Ospedaliera Civile M.P. Arezzo, Ragusa, Italy 12 Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece 13 Public Health Division of Gipuzkoa, Health Department of the Basque Country, San Sebastian, Spain 14 Public Health Institute of Navarra, Pamplona, Spain 15 Epidemiology department (SERC), Catalan Institute of Oncology, Barcelona, Spain 16 Public Health and Health Planning Directorate, Asturias, Spain 17 Andalusian School of Public Health, Granada, Spain 18 Department of Epidemiology, Murcia Health Council, Murcia, Spain 19 MRC Dunn Human Nutrition Unit, Welcome Trust/MRC Building, Cambridge, UK 20 Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK 21 Inserm E3N-EPIC, Institute Gustave Roussy, Villejuif, France 22 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark 23 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark 24 Institute of Community Medicine, University of Tromso, Tromso, Norway 25 Biomedical Sciences/Pathology and Department of Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden 26 Department of Medicine, Lund University, Malmö, Sweden 27 Department of Epidemiology & Public Health, Faculty of Medicine, Imperial College London, St Mary’s Campufs, Norfolk Place, London, UK

(Requests for offprints should be addressed to R Kaaks who is now at Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelburg, Germany; Email: r.kaaks@dkfz-heidelberg.de)

We set out to study the relationship between circulating levels of IGF-I and its major binding protein (IGFBP-3) in relation to ovarian cancer risk. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.

Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum samples of 214 women who subsequently developed ovarian cancer, and 388 matched control subjects. Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels. For all women, there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer.

However, among women diagnosed with ovarian cancer aged 55 or younger, the relative risk was higher in the middle or top tertiles of serum IGF-I, when compared with women in the lowest tertile (odds ratios (OR) = 1.8 (95%CI 0.7–4.3) and OR = 2.4 (95%CI 0.9–6.4); Ptrend = 0.08) respectively.

These results were adjusted for body mass index, previous hormone use, fertility problems, and parity. Restricting the analysis to women who were premenopausal at blood donation, relative risks for ovarian cancer diagnosed before age 55 were higher (OR = 5.1 (95%CI 1.5–18.2) and OR = 5.6 (95%CI 1.5–20.8) respectively, for second and third tertiles; Ptrend = 0.02). Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates.

Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I, but less strong and statistically not significant. In women aged over 55, there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk.

Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age.

Endocrine-Related Cancer 14 (1) 81-90 DOI: 10.1677/erc.1.01264

Ann's NOTE: Remember Bovine Growth Hormone - theoretically it is responsible for increased IGF-1 in milk. I personally think adult women should not drink cow's milk unless it is organic (and thus BGH-free).

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