TY - JOUR
T1 - 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
AU - Lindström, Sara
AU - Ma, Jing
AU - Altshuler, David
AU - Giovannucci, Edward
AU - Riboli, Elio
AU - Albanes, Demetrius
AU - Allen, Naomi E.
AU - Berndt, Sonja I.
AU - Boeing, Heiner
AU - Bueno-de-Mesquita, H. Bas
AU - Chanock, Stephen J.
AU - Dunning, Alison M.
AU - Feigelson, Heather Spencer
AU - Gaziano, J. Michael
AU - Haiman, Christopher A.
AU - Hayes, Richard B.
AU - Henderson, Brian E.
AU - Hunter, David J.
AU - Kaaks, Rudolf
AU - Kolonel, Laurence N.
AU - Marchand, Loic Le
AU - Martínez, Carmen
AU - Overvad, Kim
AU - Siddiq, Afshan
AU - Stampfer, Meir
AU - Stattin, Pär
AU - Stram, Daniel O.
AU - Thun, Michael J.
AU - Trichopoulos, Dimitrios
AU - Tumino, Rosario
AU - Virtamo, Jarmo
AU - Weinstein, Stephanie J.
AU - Yeager, Meredith
AU - Kraft, Peter
AU - Freedman, Matthew L.
PY - 2010/9
Y1 - 2010/9
N2 - 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.Along-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.
AB - 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.Along-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.
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U2 - 10.1210/jc.2009-1911
DO - 10.1210/jc.2009-1911
M3 - Article
C2 - 20534771
AN - SCOPUS:77956596257
SN - 0021-972X
VL - 95
SP - E121-E127
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -