2 results on '"Lindstroem, S"'
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2. A Large Study of Androgen Receptor Germline Variants and Their Relation to Sex Hormone Levels and Prostate Cancer Risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
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Peter Kraft, Loic Le Marchand, H. Bas Bueno-de-Mesquita, Pär Stattin, Stephen J. Chanock, Daniel O. Stram, Stephanie J. Weinstein, Alison M. Dunning, Jarmo Virtamo, Heather Spencer Feigelson, Richard B. Hayes, Rosario Tumino, Matthew L. Freedman, Kim Overvad, David Altshuler, Demetrius Albanes, Jing Ma, Meredith Yeager, Heiner Boeing, Carmen Martinez, Meir J. Stampfer, Rudolf Kaaks, David J. Hunter, Brian E. Henderson, Elio Riboli, Michael J. Thun, Afshan Siddiq, Edward Giovannucci, Christopher A. Haiman, Laurence N. Kolonel, Naomi E. Allen, Sara Lindström, J. Michael Gaziano, Sonja I. Berndt, Dimitrios Trichopoulos, [Lindstroem,S, Hunter,DJ, Kraft,P] Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [Lindstroem,S, Stampfer,M, Trichopoulos,D, Kraft,P] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [Giovannucci,E, Stampfer,M] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. [Kraft,P] Department of Biostatisctics, Harvard School of Public Health, Boston, Massachusetts, USA. [Ma,J, Stampfer,M] Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA. [Altshuler,D] Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, Department of Genetics, Harvard Medical School, Boston, Massachusetts, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts. [Riboli,E, Siddiq,A] Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College, London, United Kingdom. [Albanes,D, Berndt,SI, Chanock,SJ, Hayes,RB, Weinstein,SJ] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. [Allen,NE] Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. [Boeing,H] German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Dunning,AM] Department of Oncology, University of Cambridge, Cambridge, United Kingdom. [Feigelson,HS, Thun,MJ] Department of Epidemiology, American Cancer Society, Atlanta, Georgia. [Feigelson, HS] Kaiser Permanente, Denver, Colorado. [Gaziano,JM] Massachusetts Veterans Epidemiology and Research Information Center and Geriatric Research, Education, Clinical Center, Boston Veterans Affairs Healthcare System, Boston, Massachusetts, Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts. [Haiman,CA, Henderson,BE, Stram, DO] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. [Hayes,RB] Division of Epidemiology, New York University Langone Medical Center, New York, New York. [Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Kolonel,LN, Le Marchand,L]Cancer Research Center, University of Hawaii, Honolulu, Hawaii. [Martinez,C] Andalusian School of Public Health. Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, Granada, Spain. [Overvad,K] Clinical Epidemiology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Stattin,P] Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden. [Tumino,R] Cancer Registry Azienda Ospedaliera 'Civile M.P.Arezzo', Ragusa, Italy. [Virtamo,J] Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. [Yeager,M] Core Genotyping Facility, Advanced Technology Program, SAIC Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland. [Freedman,ML] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, and This work was supported by National Cancer Institute cooperative agreements UO1-CA98233, UO1-CA98710, UO1-CA98216, and UO1-CA98758, and by the Intramural Research Program of National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics. S.L. is supported by the Swedish Research Council (Vetenskapsrådet).
- Subjects
Male ,Oncology ,Neoplasias de la próstata ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,urologic and male genital diseases ,Biochemistry ,Germline ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies [Medical Subject Headings] ,Cohort Studies ,Androgen deprivation therapy ,Prostate cancer ,Endocrinology ,Sex hormone-binding globulin ,Trinucleotide Repeats ,Receptores androgénicos ,Gonadal Steroid Hormones ,Prostate cancer risk ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings] ,General Medicine ,Middle Aged ,Receptors, Androgen ,Cohort ,Original Article ,Female ,Health Care::Health Care Economics and Organizations::Organizations::Government::Federal Government::United States Government Agencies::United States Dept. of Health and Human Services::National Institutes of Health (U.S.)::National Cancer Institute (U.S.) [Medical Subject Headings] ,Risk ,medicine.medical_specialty ,Estudios de cohortes ,Breast Neoplasms ,Biology ,Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings] ,Germline mutation ,Translational Highlights from Jcem ,Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings] ,Internal medicine ,Carcinoma ,medicine ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings] ,Genetic Association Studies ,Germ-Line Mutation ,Aged ,Hormonas esteroides gonadales ,Estudios de asociación genética ,Biochemistry (medical) ,Case-control study ,Prostatic Neoplasms ,Cancer ,medicine.disease ,National Cancer Institute (U.S.) ,United States ,Androgen receptor ,Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones [Medical Subject Headings] ,Case-Control Studies ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Androgen [Medical Subject Headings] ,biology.protein - Abstract
Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 × 10−5) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol.
- Published
- 2010
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