1. Hormone treatment, estrogen receptor polymorphisms and mortality: a prospective cohort study
- Author
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Jacqueline Scali, Marianne Canonico, Jean-François Dartigues, Laure Carcaillon, Marie-Laure Ancelin, Carole Dufouil, Pierre-Yves Scarabin, Isabelle Carrière, Joanne Ryan, Karen Ritchie, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculty of Medicine, Imperial College London, The Three-City (3C) Study is conducted under a partnership agreement between the Institut National de la Sante' et de la Recherche Médicale, the Victor Segalen Bordeaux II University and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and first phase of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé , MGEN, Institut de la Longéviteé , Agence Française de Sécurité Sanitaire des Produits de Santé , the Regional Governments of Aquitaine, Bourgogne and Languedoc-Roussillon and, the Fondation de France, the Ministry of Research-Inserm Programme 'Cohorts and collection of biological material'. Part of this project is financed by grants from the Agence Nationale de la Recherche (projects ANR 2007-LVIE-004 and 2007-LVIE-005-01), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Villebrun, Dominique
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Anatomy and Physiology ,Epidemiology ,medicine.medical_treatment ,Cancer Treatment ,Estrogen receptor ,Physiology ,0302 clinical medicine ,Endocrinology ,Risk of mortality ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,MESH: Aged ,education.field_of_study ,Multidisciplinary ,MESH: Hormone Replacement Therapy ,Obstetrics and Gynecology ,Hormone replacement therapy (menopause) ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,3. Good health ,Menopause ,Oncology ,Receptors, Estrogen ,MESH: Receptors, Estrogen ,Medicine ,Female ,Research Article ,medicine.medical_specialty ,Drugs and Devices ,Clinical Research Design ,Hormone Replacement Therapy ,Science ,Population ,Endocrine System ,03 medical and health sciences ,Internal medicine ,MESH: Polymorphism, Genetic ,medicine ,Humans ,Mortality ,education ,Biology ,Aged ,Clinical Genetics ,MESH: Humans ,Polymorphism, Genetic ,MESH: Mortality ,Endocrine Physiology ,Population Biology ,Proportional hazards model ,business.industry ,Computational Biology ,medicine.disease ,MESH: Prospective Studies ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Geriatrics ,Women's Health ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Estrogen receptor alpha ,MESH: Female ,030217 neurology & neurosurgery ,Population Genetics - Abstract
International audience; BACKGROUND: The association between hormone treatment (HT) and mortality remains controversial. This study aimed to determine whether the risk of mortality associated with HT use varies depending on the specific characteristics of treatment and genetic variability in terms of the estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: A prospective, population-based study of 5135 women aged 65 years and older who were recruited from three cities in France and followed over six years. Detailed information related to HT use was obtained and five estrogen receptor polymorphisms were genotyped. The total follow-up was 25,436 person-years and during this time 352 women died. Cancer (36.4%) and cardiovascular disease (19.3%) were the major causes of death. Cox proportional hazards models adjusted for age, education, centre, living situation, comorbidity, depression, physical and mental incapacities, indicated no significant association between HT and mortality, regardless of the type or duration of treatment, or the age at initiation. However, the association between HT and all-cause or cancer-related mortality varied across women, with significant interactions identified with three estrogen receptor polymorphisms (p-values = 0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1 rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI: 0.18-0.97), while in stark contrast, those homozygous for the T allele had a significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23-8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572. CONCLUSIONS/SIGNIFICANCE: The risk of mortality was not associated with HT duration, type or age at initiation. It was however not equal across all women, with some women appearing genetically more vulnerable to the effects of HT in terms of their estrogen receptor genotype. These findings, if confirmed in another independent study, may help explain the differential susceptibility of women to the beneficial or adverse effects of HT.
- Published
- 2012
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