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
Data(s) |
07/05/2012
07/05/2012
01/09/2010
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Resumo |
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. 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). |
Identificador |
Lindström 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):E121-7 0021-972X http://hdl.handle.net/10668/392 20534771 10.1210/jc.2009-1911 |
Idioma(s) |
es |
Publicador |
Endocrine Society |
Relação |
Journal of Clinical Endocrinology and Metabolism http://jcem.endojournals.org/content/95/9/E121.long |
Direitos |
Acceso abierto |
Palavras-Chave | #Neoplasias de la próstata #Hormonas esteroides gonadales #Receptores androgénicos #Estudios de asociación genética #Estudios de cohortes #Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms #Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Androgen #Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies #Medical 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 Studies #Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/published Artículo |