The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer : results from the EPIC Cohort
Roura, Esther (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Travier, Noémie (Institut Català d'Oncologia)
Waterboer, Tim (German Cancer Research Center (DKFZ), Heidelberg, Germany)
De Sanjose, Silvia (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Bosch José, Francesc Xavier 1947- (Institut Català d'Oncologia)
Pawlita, Michael (German Cancer Research Center (DKFZ), Heidelberg, Germany)
Pala, Valeria (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy)
Weiderpass, Elisabete (Folkhälsan Research Center, Helsinki, Finland)
Margall, Núria (Institut d'Investigació Biomèdica Sant Pau)
Dillner, Joakim (Karolinska Institutet (Estocolm, Suècia))
Gram, Inger T. (UiT The Arctic University of Norway, Tromsø, Norway)
Tjønneland, Anne (Danish Cancer Society Research Center, Copenhagen, Denmark)
Munk, Christian (Danish Cancer Society Research Center, Copenhagen, Denmark)
Palli, Domenico (Cancer Research and Prevention Institute-ISPO, Florence, Italy)
Khaw, Kay-Tee (University of Cambridge)
Overvad, Kim (Aarhus University, Aarhus, Denmark)
Clavel-Chapelon, Françoise (Institut Gustave Roussy (Villejuif, França))
Mesrine, Sylvie (Institut Gustave Roussy (Villejuif, França))
Fournier, Agnès (Institut Gustave Roussy (Villejuif, França))
Fortner, Renée T. (German Cancer Research Center (DKFZ), Heidelberg, Germany)
Ose, Jennifer (German Cancer Research Center (DKFZ), Heidelberg, Germany)
Steffen, Annika (German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany)
Trichopoulou, Antonia (Hellenic Health Foundation, Athens, Greece)
Lagiou, Pagona (Harvard School of Public Health, Boston, United States of America)
Orfanos, Philippos (University of Athens Medical School, Athens, Greece)
Masala, Giovanna (Cancer Research and Prevention Institute-ISPO, Florence, Italy)
Tumino, Rosario ("Civic-M.P. Arezzo" Hospital, Ragusa, Italy)
Sacerdote, Carlotta (Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy)
Polidoro, Silvia (Human Genetics Foundation (HuGeF), Turin, Italy)
Mattiello, Amalia (Federico II University, Naples, Italy)
Lund, Eiliv (UiT The Arctic University of Norway, Tromsø, Norway)
Peeters, Petra H. (University Medical Center Utrecht, Utrecht, The Netherlands)
Bueno-de-Mesquita, H. Bas (University of Malaya, Kuala Lumpur, Malaysia)
Quirós, J. Ramón (Dirección de Salud Pública de Asturias)
Sánchez, María-José (Instituto de Investigación Sanitaria de Granada)
Navarro Sánchez, Carmen (Universidad de Murcia)
Barricarte, Aurelio (Instituto de Investigación Sanitaria de Navarra)
Larrañaga, Nerea (Biodonostia Osasun Ikerketako Institutura (País Basc))
Ekström, Johanna (Lund University, Medicon Village, Lund, Sweden)
Lindquist, David (Department of Radiation Sciences, Umeå University, Umeå, Sweden)
Idahl, Annika (Umeå University, Umeå, Sweden)
Travis, Ruth C. (University of Oxford, Oxford, United Kingdom)
Merritt, Melissa A. (Imperial College London, London, United Kingdom)
Gunter, Marc J. (Imperial College London, London, United Kingdom)
Rinaldi, Sabina (International Agency for Research on Cancer, Lyon, France)
Tommasino, Massimo (International Agency for Research on Cancer, Lyon, France)
Franceschi, Silvia (International Agency for Research on Cancer, Lyon, France)
Riboli, Elio (Imperial College London, London, United Kingdom)
Castellsagué, Xavier (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0. 03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1. 6 and HR = 1. 8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0. 5, 95%CI: 0. 4-0. 8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0. 6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0. 7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
Ayudas:	Instituto de Salud Carlos III PI08/1308 Instituto de Salud Carlos III PI13/00053 Instituto de Salud Carlos III RCESP C03/09 Instituto de Salud Carlos III RTICESP C03/10 Instituto de Salud Carlos III RTIC RD06/0020/0095 Instituto de Salud Carlos III RD12/0036/0056 Instituto de Salud Carlos III RD12/0036/0018 Ministerio de Sanidad P10710130 Agència de Gestió d'Ajuts Universitaris i de Recerca 2005/SGR-00695 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-939 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-126 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1077 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-2016
Nota:	The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130)
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	PloS one, Vol. 11 (january 2016) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0147029
PMID: 26808155

17 p, 277.3 KB

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