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Maria Angela De Stefano Department of Public Health, University of Naples “Federico II”, Naples, Italy

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Tommaso Porcelli Department of Public Health, University of Naples “Federico II”, Naples, Italy

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Martin Schlumberger Department of Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

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Domenico Salvatore Department of Public Health, University of Naples “Federico II”, Naples, Italy
CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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The three deiodinase selenoenzymes are key regulators of intracellular thyroid hormone (TH) levels. The two TH-activating deiodinases (type 1 deiodinase and type 2 deiodinase (D2)) are normally expressed in follicular thyroid cells and contribute to overall TH production. During thyroid tumorigenesis, the deiodinase expression profile changes to customize intracellular TH levels to different requirements of cancer cells. Differentiated thyroid cancers overexpress the TH-inactivating type 3 deiodinase (D3), likely to reduce the TH signaling within the tumor. Strikingly, recent evidence suggests that during the late stage of thyroid tumorigenesis, D2 expression raises and this, together with a reduction in D3 expression levels, increases TH intracellular signaling in dedifferentiated thyroid cancers. These findings call into question the different functions of TH in the various stages of thyroid cancers.

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Tommaso Porcelli Department of Public Health, University of Naples ‘Federico II’, Naples, Italy

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Raffaele Ambrosio Department of Public Health, University of Naples ‘Federico II’, Naples, Italy

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Maria Angela De Stefano Department of Public Health, University of Naples ‘Federico II’, Naples, Italy

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Cristina Luongo Department of Clinical Medicine and Surgery, University of Naples ‘Federico II’, Naples, Italy

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Daniela Terracciano Department of Translational Medical Sciences, University of Naples ‘Federico II’, Naples, Italy

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Caterina Miro Department of Clinical Medicine and Surgery, University of Naples ‘Federico II’, Naples, Italy

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Monica Dentice Department of Clinical Medicine and Surgery, University of Naples ‘Federico II’, Naples, Italy

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Martin Schlumberger Department of Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

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Domenico Salvatore Department of Public Health, University of Naples ‘Federico II’, Naples, Italy
CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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Treatment with tyrosine kinase inhibitors (TKIs) has been associated with alterations in circulating thyroid hormone levels, possibly related to perturbations in peripheral thyroid hormone metabolism. In this study, we evaluated the effect of the multi-kinase inhibitor vandetanib on the expression of the three deiodinase selenoenzymes, responsible for the thyroid hormone activation (type 1 and type 2 deiodinases) or for its inactivation (type 3 deiodinase). Here, we show that the multi-kinase inhibitor vandetanib determines a strong cell-specific downregulation of type 2 deiodinase (D2) expression and a significant reduction in D2 enzymatic activity. This occurs in the diffused population of fibro/adipogenic progenitors, which reside in different tissues – including the muscles – and normally express D2. Given the widespread diffusion of mesenchymal cells within the body, our results may explain at least partially the alterations in thyroid hormone levels that occur in vandetanib-treated patients. Our findings represent a step forward into the understanding of the mechanisms by which TKIs induce hypothyroidism and identify a resident cell population in which such an effect takes place.

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Maria Angela De Stefano Department of Public Health, University of Naples ’Federico II’, Naples, Italy

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Tommaso Porcelli Department of Public Health, University of Naples ’Federico II’, Naples, Italy

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Raffaele Ambrosio IRCCS SDN, Naples, Italy

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Cristina Luongo Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy

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Maddalena Raia CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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Martin Schlumberger Department of Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

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Domenico Salvatore Department of Public Health, University of Naples ’Federico II’, Naples, Italy
CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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Anaplastic thyroid cancer (ATC) is a rare thyroid tumor that frequently originates from the dedifferentiation of a well-differentiated papillary or follicular thyroid cancer. Type 2 deiodinase (D2), responsible for the activation of the thyroid hormone thyroxine into tri-iodothyronine (T3), is expressed in normal thyroid cells and its expression is strongly downregulated in papillary thyroid cancer. In skin cancer, D2 has been associated with cancer progression, dedifferentiation, and epithelial–mesenchymal transition. Here, we show that D2 is highly expressed in anaplastic compared to papillary thyroid cancer cell lines and that D2-derived T3 is required for ATC cell proliferation. D2 inhibition is associated with G1 growth arrest and induction of cell senescence, together with reduced cell migration and invasive potential. Finally, we found that mutated p5372R(R248W), frequently found in ATC, is able to induce D2 expression in transfected papillary thyroid cancer cells. Our results show that the action of D2 is crucial for ATC proliferation and invasiveness, providing a potential new therapeutic target for the treatment of ATC.

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Livia Lamartina Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma Sapienza, Roma, Italy

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Giorgio Grani Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma Sapienza, Roma, Italy

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Emanuela Arvat Dipartimento di Scienze Mediche, Università di Torino, Torino, Italy

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Alice Nervo Dipartimento di Scienze Mediche, Università di Torino, Torino, Italy

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Maria Chiara Zatelli Unità Operativa di Endocrinologia e Malattie del Ricambio, Azienda Ospedaliera Universitaria di Ferrara, Ferrara, Italy

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Roberta Rossi Unità Operativa di Endocrinologia e Malattie del Ricambio, Azienda Ospedaliera Universitaria di Ferrara, Ferrara, Italy

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Efisio Puxeddu Dipartimento di Medicina, Università di Perugia, Perugia, Italy

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Silvia Morelli Dipartimento di Medicina, Università di Perugia, Perugia, Italy

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Massimo Torlontano Dipartimento di Scienze Mediche, Ospedale Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo, Italy

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Michela Massa Dipartimento di Scienze Mediche, Ospedale Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo, Italy

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Rocco Bellantone Cattedra di Chirurgia Endocrina, Area di Endocrinologia e Malattie Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy

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Alfredo Pontecorvi Cattedra di Endocrinologia, Area di Endocrinologia e Malattie Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy

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Teresa Montesano Unità di Medicina Nucleare, Università di Roma Sapienza, Roma, Italy

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Loredana Pagano Unità di Endocrinologia, Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale, Novara, Italy

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Lorenzo Daniele Unità di Patologia, Ospedale Mauriziano Umberto I di Torino, Torino, Italy

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Laura Fugazzola Divisione di Malattie Endocrine e Metaboliche, Istituto Auxologico Italiano IRCCS, Milano, Italy
Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, Italy

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Graziano Ceresini Dipartimento di Medicina e Chirurgia, Università di Parma, Parma, Italy

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Rocco Bruno Unità di Endocrinologia, Ospedale di Tinchi-Pisticci, Matera, Italy

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Ruth Rossetto Divisione di Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Ospedale Molinette, A.O.U. Città della Salute e della Scienza di Torino, Università di Torino, Torino, Italy

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Salvatore Tumino Dipartimento di Medicina Clinica e Sperimentale, Università di Catania, Catania, Italy

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Marco Centanni Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche, Università di Roma Sapienza, Latina, Italia

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Domenico Meringolo Unità Operativa Semplice Dipartimentale, Ospedale Bentivoglio, Ausl Bologna, Bologna, Italy

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Maria Grazia Castagna Dipartimento di Scienze Mediche, Chirurgiche e Neurologiche, Università di Siena, Siena, Italy

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Domenico Salvatore Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli ‘Federico II’, Napoli, Italy

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Antonio Nicolucci Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy

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Giuseppe Lucisano Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy

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Sebastiano Filetti Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma Sapienza, Roma, Italy

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Cosimo Durante Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma Sapienza, Roma, Italy

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Petra H M Peeters
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Annekatrin Lukanova
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Naomi Allen
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Franco Berrino
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Tim Key
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Laure Dossus
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Sabina Rinaldi
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Carla H van Gils
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H Bas Bueno-de-Mesquita
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Heiner Boeing
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Mandy Schulz
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Jenny Chang-Claude
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Jakob Linseisen
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Salvatore Panico
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Carlotta Sacerdote
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Domenico Palli
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Rosario Tumino
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Antonia Trichopoulou
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Dimitrios Trichopolos
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Christina Bamia
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Nerea Larranaga
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Eva Ardanaz
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Guillem Pera
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J Ramón Quirós
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Carmen Martínez-García
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Carmen Navarro
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Sheila A Bingham
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Kay-Tee Khaw
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Françoise Clavel
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Anne Tjonneland
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Anja Olsen
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Kim Overvad
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Mette S Tetsche
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Eiliv Lund
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Eva Lundin
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Göran Berglund
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Elio Riboli
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R Kaaks
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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); P trend = 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; P trend = 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.

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Naomi E Allen
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Timothy J Key
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Laure Dossus Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Sabina Rinaldi Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Anne Cust Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK
Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Annekatrin Lukanova Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Petra H Peeters Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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N Charlotte Onland-Moret Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Petra H Lahmann Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Franco Berrino Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Salvatore Panico Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Nerea Larrañaga Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Guillem Pera Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Maria-José Tormo Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Maria-José Sánchez Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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J Ramón Quirós Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Eva Ardanaz Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Anne Tjønneland Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Anja Olsen Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Jenny Chang-Claude Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Jakob Linseisen Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Mandy Schulz Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Heiner Boeing Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Eva Lundin Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Domenico Palli Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Kim Overvad Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Françoise Clavel-Chapelon Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Marie-Christine Boutron-Ruault Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Sheila Bingham Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Kay-Tee Khaw Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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H Bas Bueno-de-Mesquita Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Antonia Trichopoulou Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Dimitiros Trichopoulos Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Androniki Naska Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Rosario Tumino Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Elio Riboli Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Rudolf Kaaks Cancer Research UK Epidemiology Unit, Nutrition and Hormones Group, University of Sydney, Julius Center for Health Sciences and Primary Care, Medical Research Council Human Nutrition Research, Epidemiology Unit, Department of Clinical and Experimental Medicine, Public Health Department of Gipuzkoa, Department of Epidemiology, Consejería de Sanidad y Política Social, Andalusian School of Public Health, Public Health & Health Planning Directorate, Instituto de Salud Pública de Navarra, Institute of Cancer Epidemiology, Division of Cancer Epidemiology, German Institute of Human Nutrition, Department of Nutritional Research, Molecular and Nutritional Epidemiology Unit, Department of Clinical Epidemiology, Inserm E3N-EPIC, MRC Dunn Human Nutrition Unit, Clinical Gerontology Unit, National Institute of Public Health and the Environment, Department of Hygiene and Epidemiology, Cancer Registry, Cancer Epidemiology and Prevention, University of Oxford, Oxford, UK

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Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case–control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50–4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20–3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98–2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88–2.36; P=0.05) and 2.05 (95% CI 1.23–3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34–0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.

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Anne E Cust
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Rudolf Kaaks
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Christine Friedenreich
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Anne Tjønneland
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Anja Olsen
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Kim Overvad
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Marianne Uhre Jakobsen
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Véronique Chajès
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Françoise Clavel-Chapelon
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Marie-Christine Boutron-Ruault
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Jakob Linseisen
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Annekatrin Lukanova
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Heiner Boeing
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J R Quirós
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Fränzel J B van Duijnhoven
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Elio Riboli
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To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38–0.97), P trend = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99–2.90), P trend = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46–4.66), P trend = 0.0006, P heterogeneity = 0.13) and never-users of exogenous hormones (P heterogeneity = 0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51–2.97)), which increased with the number of MetS factors (P trend = 0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P interaction = 0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.

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Laure Dossus Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Sabina Rinaldi Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Susen Becker Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Annekatrin Lukanova Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Anne Tjonneland Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Anja Olsen Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Jakob Stegger Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Kim Overvad Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Nathalie Chabbert-Buffet Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Aida Jimenez-Corona Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Francoise Clavel-Chapelon Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Sabine Rohrmann Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Birgit Teucher Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Heiner Boeing Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Madlen Schütze Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Antonia Trichopoulou Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Vassiliki Benetou Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Pagona Lagiou Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Domenico Palli Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Franco Berrino Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Salvatore Panico Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Rosario Tumino Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Carlotta Sacerdote Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Maria-Luisa Redondo Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Noémie Travier Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Maria-Jose Sanchez Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Jone M Altzibar Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Maria-Dolores Chirlaque Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Eva Ardanaz Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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H Bas Bueno-de-Mesquita Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Fränzel J B van Duijnhoven Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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N Charlotte Onland-Moret Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Petra H M Peeters Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Goran Hallmans Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Eva Lundin Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Kay-Tee Khaw Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Nicholas Wareham Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Naomi Allen Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Tim J Key Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Nadia Slimani Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Pierre Hainaut Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Dora Romaguera Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Teresa Norat Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Elio Riboli Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Rudolf Kaaks Division of Cancer Epidemiology, Section of Nutrition and Metabolism, Department of Obstetrics and Gynecology, Institute of Cancer Epidemiology, Department of Cardiology, Department of Epidemiology, Obstetrics and Gynecology Department, Inserm, National Institute of Public Health, Department of Epidemiology, WHO Collaborating Center for Food and Nutrition Policies, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Epidemiology Unit, Department of Clinical and Experimental Medicine, Cancer Registry and Histopathology Unit, Center for Cancer Prevention (CPO Piedmont), Human Genetic Foundation (Hugef), Public Health and Participation Directorate, Unit of Nutrition, Andalusian School of Public Health, CIBER Epidemiologia y Salud Publica (CIBERESP), Department of Public Health of Guipuzkoa, Department of Epidemiology, Public Health Institute of Navarra, National Institute for Public Health and the Environment (RIVM), Julius Center for Health Sciences and Primary Care, Department of Public Health and Clinical Medicine, Department of Medical Biosciences, Department of Public Health and Primary Care, MRC Epidemiology Unit, Cancer Epidemiology Unit, Section of Mechanisms of Carcinogenesis, Department of Epidemiology and Biostatistics, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03–2.41, P trend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, P trend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, P trend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.

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