Lindström, SaraMa, JingAltshuler, DavidGiovannucci, EdwardRiboli, ElioAlbanes, DemetriusAllen, Naomi EBerndt, Sonja IBoeing, HeinerBueno de Mesquita, H BasChanock, Stephen JDunning, Alison MSpencer Feigelson, HeatherGaziano, J MichaelHaiman, Christopher AHayes, Richard BHenderson, Brian EHunter, David JKaaks, RudolfKolonel, Laurence NLe Marchand, LoicMartínez, CarmenOvervad, KimSiddiq, AfshanStampfer, MeirStattin, PärStram, Daniel OThun, Michael JTrichopoulos, DimitriosTumino, RosarioVirtamo, JarmoWeinstein, Stephanie JYeager, MeredithKraft, PeterFreedman, Matthew L2012-05-072012-05-072010-09-01Lindström S, Ma J, Altshuler D, Giovannucci E, Riboli E, Albanes D, et al. 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. J Clin Endocrinol Metab. 2010 Sep;95(9):E121-7http://hdl.handle.net/10668/392Background: 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.esNeoplasias de la próstataHormonas esteroides gonadalesReceptores androgénicosEstudios de asociación genéticaEstudios de cohortesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic NeoplasmsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, AndrogenMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid HormonesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association StudiesMedical Subject Headings::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::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort StudiesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studiesresearch article20534771open access10.1210/jc.2009-19110021-972X