title: Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium.
abstract: Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case-control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2= 1.12; 95% confidence interval 1.02-1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2= 1.40 (1.03-1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2= 0.76 (0.60-0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC.Cancer Res; 77(14); 3951-60. ©2017 AACR.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany.|Department of Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ose
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Schock
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Huddinge, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.affiliation: Department of Obstetrics and Gynecology, New York University School of Medicine; Perlmutter Cancer Center, New York University, New York, New York.|Department of Population Health and Environmental Medicine, New York University School of Medicine; Perlmutter Cancer Center, New York University, New York, New York.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Arslan
authors.affiliation: Department of Population Health and Environmental Medicine, New York University School of Medicine; Perlmutter Cancer Center, New York University, New York, New York.
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Kathy
authors.initials: K
authors.lastname: Helzlsouer
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
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, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
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: Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
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, United Kingdom.
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, United Kingdom.
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, Maryland.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany. r.fortner@dkfz.de.
authors.forename: Renée T
authors.initials: RT
authors.lastname: Fortner
mesh_terms: D000728:Androgens / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000145:classification* / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors
chemical_list: D000728:Androgens