title: Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium.
abstract: OBJECTIVE
  Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results.
  
  
  METHODS
  We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).
  
  
  RESULTS
  Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [ORlog2= 0.82; CI 0.72-0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, phet= 0.62), menopausal status at blood collection (phet= 0.79), or age at diagnosis (phet= 0.60).
  
  
  CONCLUSIONS
  These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Baden-Württemberg, Germany.|Department of Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ose
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Baden-Württemberg, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Schock
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Helzlsouer
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
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: Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.|Gustave Roussy, 94805, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Nutrition and Health, University of Athens Medical School, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.|Department of Research, Cancer Registry of Norway, Oslo, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.|Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.|CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: Department of Clinical Sciences, Obstetrics and Gynecology, Umea University, Umea, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Idahl
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merritt
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Baden-Württemberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Baden-Württemberg, Germany. r.fortner@dkfz-heidelberg.de.
authors.forename: Renée T
authors.identifier: http://orcid.org/0000-0002-1426-8505
authors.initials: RT
authors.lastname: Fortner
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D007334:Insulin-Like Growth Factor I
keywords: Developmental pathways; Epithelial ovarian cancer; Histological subtypes; IGF-I