title: Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer.
abstract: Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden h.schock@dkfz.de.
authors.forename: Helena
authors.initials: H
authors.lastname: Schock
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Heljä-Marja
authors.initials: HM
authors.lastname: Surcel
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Hans-Åke
authors.initials: HÅ
authors.lastname: Lakso
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Renée Turzanski
authors.initials: RT
authors.lastname: Fortner
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer
authors.forename: Paolo
authors.initials: P
authors.lastname: Toniolo
authors.affiliation: Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden Division of Cancer EpidemiologyGerman Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, GermanyDepartment of Medical BiosciencesUmeå University, Umeå, SwedenUnit of Sexual and Reproductive HealthNational Institute for Health and Welfare, Oulu, FinlandDepartments of Population Health and Environmental MedicineNew York University School of Medicine, New York, New York, USANew York University Cancer InstituteNew York University School of Medicine, New York, New York, USAFinnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer Research, Helsinki, FinlandSchool of Health SciencesUniversity of Tampere, Tampere, FinlandDepartment of Obstetrics and GynecologyNew York University School of Medicine, New York, New York, USAInstitute of Social and Preventive MedicineCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandPublic Health and Clinical Medicine: Nutritional ResearchUmeå University, Umeå, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D016889:Endometrial Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D012739:Gonadal Steroid Hormones / Q000009:adverse effects / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D011247:Pregnancy; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012739:Gonadal Steroid Hormones
keywords: case–control study; ovarian neoplasms; pregnancy; prospective study; sex steroids