title: Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.
abstract: Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Renée T
authors.identifier: 0000-0002-1426-8505
authors.initials: RT
authors.lastname: Fortner
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.|Department of Biostatistics, Hacettepe University, Ankara, Turkey.
authors.forename: Meric
authors.initials: M
authors.lastname: Konar
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Unit of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: Unit of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Hansen
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.|Université Paris Sud, UMRS 1018, Villejuif, France.|Gustave Roussy, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.|Université Paris Sud, UMRS 1018, Villejuif, France.|Gustave Roussy, Villejuif, France.|Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.|Université Paris Sud, UMRS 1018, Villejuif, France.|Gustave Roussy, Villejuif, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Benetou
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Philippos
authors.initials: P
authors.lastname: Orfanos
authors.affiliation: Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.affiliation: Cancer Registry and Histopathology Unit, "Civic-M.P.Arezzo" Hospital, ASP Ragusa, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.|Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H B As
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.|MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.|Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Inger T
authors.initials: IT
authors.lastname: Gram
authors.affiliation: Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.|Department of Obstetrics and Gynecology, University Hospital Northern Norway, Tromsø, Norway.
authors.forename: Oxana
authors.initials: O
authors.lastname: Gavrilyuk
authors.affiliation: Public Health Directorate, Asturias, Spain.
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.affiliation: Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: José
authors.initials: J
authors.lastname: Maria Huerta
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Navarra Public Health Institute, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.affiliation: Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Leila
authors.initials: L
authors.lastname: Lujan-Barroso
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.Granada. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Sánchez-Cantalejo
authors.affiliation: Division of Surgery, Clinical Sciences Malmö, Lund University, Lund, Sweden.
authors.forename: Salma Tunå
authors.initials: ST
authors.lastname: Butt
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.affiliation: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.|Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Idahl
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.affiliation: Cancer Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Cambridge, United Kingdom.
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Gunter
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merritt
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tzoulaki
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D016022:Case-Control Studies; D015897:Comorbidity; D016207:Cytokines / Q000097:blood; D016889:Endometrial Neoplasms / Q000097:blood / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006728:Hormones / Q000097:blood; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D012306:Risk; D018570:Risk Assessment; D016037:Single-Blind Method; D011795:Surveys and Questionnaires
chemical_list: D014408:Biomarkers, Tumor; D001786:Blood Glucose; D001798:Blood Proteins; D016207:Cytokines; D006728:Hormones; D008055:Lipids
keywords: adipokines; cytokines; endometrial cancer; growth factors; inflammatory markers; lipids; metabolic markers; prospective cohort; risk prediction; sex steroids