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      Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

      research-article
      Endogenous Hormones and Breast Cancer Collaborative Group 1 , 2
      British Journal of Cancer
      Nature Publishing Group
      breast cancer, hormones, oestrogens, androgens, sex hormone-binding globulin

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          Abstract

          Background:

          Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.

          Methods:

          Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.

          Results:

          Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.

          Conclusion:

          Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

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          Most cited references67

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          Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies.

          Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women. We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate. The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis. Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women.
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            Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

            Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.
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              Tobacco smoke and involuntary smoking.

              (2004)
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                23 August 2011
                19 July 2011
                23 August 2011
                : 105
                : 5
                : 709-722
                Affiliations
                [1 ]simpleEndogenous Hormones and Breast Cancer Collaborative Group, Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford , Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, UK
                Author notes
                [2]

                See end of the paper for members and affiliations of all authors from the Endogenous Hormones and Breast Cancer Collaborative Group.

                [‡]

                Co-authors at secretariat TJ Key, PN Appleby, GK Reeves, Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK: AW Roddam, Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK, and Global Biostatistics and Epidemiology, Amgen Ltd, Uxbridge, UK. Co-authors from collaborating studies CLUE I, Washington County, MD, USA: KJ Helzlsouer, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA, and Prevention and Research Center, Mercy Medical Center, Baltimore, MD, USA; AJ Alberg, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, and Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA; and DE Rollison, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. Columbia, MO, USA: JF Dorgan, Fox Chase Cancer Center, Philadelphia, PA, USA, and LA Brinton, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. EPIC, Europe: K Overvad, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; R Kaaks, DKFZ, Heidelberg, Germany; A Trichopoulou, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece, and Hellenic Health Foundation, Athens, Greece; F Clavel-Chapelon, Centre for Research in Epidemiology and Population Health, Inserm U1018 and Paris South University, UMRS1018, IGR, Villejuif, France; S Panico, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy; EJ Duell, Unit of Nutrition Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain; PHM Peeters, Julius Center of Health Sciences and Primary Care, Julius Center, University Medical Center, Utrecht, The Netherlands, and Imperial College, London, UK; S Rinaldi, International Agency for Research on Cancer, Lyon, France; and E Riboli, Imperial College, London, UK. Guernsey, UK: IS Fentiman, Research Oncology, Guy's Hospital, London, UK, and M Dowsett, Academic Department of Biochemistry, Institute of Cancer Research, London, UK. Malmö/Umeå, Sweden: J Manjer, Department of Surgery, Malmö University Hospital, Malmö, Sweden; P Lenner, Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; and G Hallmans, Department of Clinical Medicine and Public Health, Umeå University Hospital, Umeå, Sweden. MCCS, Australia: L Baglietto, DR English, GG Giles, JL Hopper and G Severi, Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia, and HA Morris, Hanson Institute, Adelaide, Australia. Nurses' Health Study, USA: SE Hankinson and SS Tworoger for the Nurses' Health Study Research Group, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. NYU WHS, USA: K Koenig and A Zeleniuch-Jacquotte, Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA; AA Arslan and P Toniolo, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA; and RE Shore, Radiation Effects Research Foundation, Hiroshima, Japan. ORDET, Italy: V Krogh, A Micheli and F Berrino, Fondazione Istituto Nazionale Tumori, Milano, Italy, and P Muti, Istituto Nazionale Tumori Regina Elena, Roma, Italy. Rancho Bernardo, USA: E Barrett-Connor and GA Laughlin, Department of Family and Preventive Medicine, University of California, San Diego, CA, USA. RERF, Japan: M Kabuto, Environmental Risk Research Division, National Institute for Environmental Studies, Ibaraki, Japan; S Akiba, Department of Public Health, Faculty of Medicine, Kagoshima University, Kagoshima, Japan; RG Stevens, Department of Community Medicine, University of Connecticut Health Center, Farmington, CT, USA; K Neriishi, Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan; and CE Land, Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. SOF, USA: JA Cauley, Department of Epidemiology, University of Pittsburgh, PA, USA; Li Yung Lui and Steven R Cummings, San Francisco Coordinating Center, California Pacific Medical Center, San Francisco, CA, USA, and the Study of Osteoporotic Fractures Research Group, San Francisco Coordinating Center, San Francisco, CA, USA. Women's Health Initiative Observational Study, USA: MJ Gunter, TE Rohan and HD Strickler, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.

                Article
                bjc2011254
                10.1038/bjc.2011.254
                3188939
                21772329
                dab23511-17de-45e8-8db5-ae50091074aa
                Copyright © 2011 Cancer Research UK

                This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 21 February 2011
                : 31 May 2011
                : 10 June 2011
                Categories
                Epidemiology

                Oncology & Radiotherapy
                sex hormone-binding globulin,breast cancer,androgens,oestrogens,hormones
                Oncology & Radiotherapy
                sex hormone-binding globulin, breast cancer, androgens, oestrogens, hormones

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