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

被引：32

作者：

Lindstroem, Sara ^{[2
,3
]}

Ma, Jing ^{[6
]}

Altshuler, David ^{[7
,8
,9
,10
,11
]}

Giovannucci, Edward ^{[4
]}

Riboli, Elio ^{[12
]}

Albanes, Demetrius ^{[13
]}

Allen, Naomi E. ^{[14
]}

Berndt, Sonja I. ^{[13
]}

Boeing, Heiner ^{[15
]}

Bueno-de-Mesquita, H. Bas ^{[16
]}

Chanock, Stephen J. ^{[13
]}

Dunning, Alison M. ^{[17
]}

Feigelson, Heather Spencer ^{[18
,19
]}

Gaziano, J. Michael ^{[20
,21
,22
]}

Haiman, Christopher A. ^{[23
]}

Hayes, Richard B. ^{[13
,24
]}

Henderson, Brian E. ^{[23
]}

Hunter, David J. ^{[2
,6
]}

Kaaks, Rudolf ^{[25
]}

Kolonel, Laurence N. ^{[26
]}

Le Marchand, Loic ^{[26
]}

Martinez, Carmen ^{[27
,28
]}

Overvad, Kim ^{[29
]}

Siddiq, Afshan ^{[12
]}

Stampfer, Meir ^{[3
,4
,6
]}

Stattin, Paer ^{[30
]}

Stram, Daniel O. ^{[23
]}

Thun, Michael J. ^{[18
]}

Trichopoulos, Dimitrios ^{[3
]}

Tumino, Rosario ^{[31
]}

Virtamo, Jarmo ^{[32
]}

Weinstein, Stephanie J. ^{[13
]}

Yeager, Meredith ^{[33
]}

Kraft, Peter ^{[2
,3
,5
]}

Freedman, Matthew L. ^{[1
,34
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[5] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA

[7] Broad Inst Massachusetts Inst Technol MIT & Harva, Program Med & Populat Genet, Cambridge, MA USA

[8] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[9] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[10] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[11] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA

[12] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Publ Hlth, London, England

[13] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[14] Univ Oxford, Canc Epidemiol Unit, Oxford, England

[15] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany

[16] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands

[17] Univ Cambridge, Dept Oncol, Cambridge, England

[18] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA

[19] Kaiser Permanente, Denver, CO USA

[20] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA

[21] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA

[22] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA

[23] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[24] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA

[25] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany

[26] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA

[27] Ctr Invest Biomed Red Epidemiol & Salud Publ, Granada, Spain

[28] Andalusian Sch Publ Hlth, Granada, Spain

[29] Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark

[30] Umea Univ, Umea, Sweden

[31] Canc Registry Azienda Osped Civile MP Arezzo, Ragusa, Italy

[32] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

[33] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA

[34] Broad Inst Harvard & MIT, Cambridge, MA USA

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2010年 / 95卷 / 09期

基金：

美国国家卫生研究院; 瑞典研究理事会;

关键词：

CAG-REPEAT POLYMORPHISM; GROWTH-FACTOR-I; GENETIC-VARIATION; REGULATING GENES; STEROID-HORMONES; ASSOCIATION; PREDICTORS; ESTROGEN; DISEASE; LENGTH;

D O I：

10.1210/jc.2009-1911

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 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. (J Clin Endocrinol Metab 95: E121-E127, 2010)

引用

页码：E121 / E127

页数：7

共 50 条

[1] Sequence variants of estrogen receptor β and risk of prostate cancer in the national cancer institute breast and prostate cancer cohort consortium
Chen, Yen-Ching
Kraft, Peter
Bretsky, Philip
Ketkar, Shamika
Hunter, David J.
Albanes, Demetrius
Altshuler, David
Andriole, Gerald
Berg, Christine D.
Boeing, Heiner
Burtt, Noel
Bueno-de-Mesquita, Bas
Cann, Howard
Canzian, Federico
Chanock, Stephen
Dunning, Alison
Feigelson, Heather S.
Freedman, Matthew
Gaziano, J. Michael
Giovannucci, Edward
Sanchez, Maria-Jose
Haiman, Christopher A.
Hallmans, Goran
Hayes, Richard B.
Henderson, Brian E.
Hirschhorn, Joel
Kaaks, Rudolf
Key, Timothy J.
Kolonel, Laurence N.
LeMarchand, Loic
Ma, Jing
Overvad, Kim
Palli, Domenico
Pharaoh, Paul
Pike, Malcolm
Riboli, Eliot
Rodriguez, Carmen
Setiawan, V. Wendy
Stampfer, Meir
Stram, Daniel O.
Thomas, Gilles
Thun, Michael J.
Travis, Ruth C.
Virtamo, Jarmo
Trichopouiou, Antonia
Wacholder, Sholom
Weinstein, Stephanie J.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (10) : 1973 - 1981
[2] Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Shui, Irene M.
Lindstroem, Sara
Kibel, Adam S.
Berndt, Sonja I.
Campa, Daniele
Gerke, Travis
Penney, Kathryn L.
Albanes, Demetrius
Berg, Christine
Bueno-de-Mesquita, H. Bas
Chanock, Stephen
Crawford, E. David
Diver, W. Ryan
Gapstur, Susan M.
Gaziano, J. Michael
Giles, Graham G.
Henderson, Brian
Hoover, Robert
Johansson, Mattias
Le Marchand, Loic
Ma, Jing
Navarro, Carmen
Overvad, Kim
Schumacher, Fredrick R.
Severi, Gianluca
Siddiq, Afshan
Stampfer, Meir
Stevens, Victoria L.
Travis, Ruth C.
Trichopoulos, Dimitrios
Vineis, Paolo
Mucci, Lorelei A.
Yeager, Meredith
Giovannucci, Edward
Kraft, Peter
EUROPEAN UROLOGY, 2014, 65 (06) : 1069 - 1075
[3] Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
McKay, James D.
McCullough, Marjorie L.
Ziegler, Regina G.
Kraft, Peter
Saltzman, Barbara S.
Riboli, Elio
Barricarte, Aurelio
Berg, Christine D.
Bergland, Goran
Bingham, Sheila
Brustad, Magritt
Bueno-de-Mesquita, H. Bas
Burdette, Laurie
Buring, Julie
Calle, Eugenia E.
Chanock, Stephen J.
Clavel-Chapelon, Francoise
Cox, David G.
Dossus, Laure
Feigelson, Heather Spencer
Haiman, Christopher A.
Hankinson, Susan E.
Hoover, Robert N.
Hunter, David J.
Husing, Anika
Kaaks, Rudolph
Kolonel, Laurence N.
Le Marchand, Loic
Linseisen, Jakob
McCarty, Catherine A.
Overvad, Kim
Panico, Salvatore
Purdue, Mark P.
Stram, Daniel O.
Stevens, Victoria L.
Trichopoulos, Dimitrios
Willett, Walter C.
Yuenger, Jeffrey
Thun, Michael J.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2009, 18 (01) : 297 - 305
[4] A comprehensive analysis of the androgen receptor gene and risk of breast cancer:: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
Cox, David G.
Blanche, Helene
Pearce, Celeste L.
Calle, Eugenia E.
Colditz, Graham A.
Pike, Malcolm C.
Albanes, Demetrius
Allen, Naomi E.
Amiano, Pilar
Berglund, Goran
Boeing, Heiner
Buring, Julie
Burtt, Noel
Canzian, Federico
Chanock, Stephen
Clavel-Chapelon, Francoise
Feigelson, Heather Spencer
Freedman, Matthew
Haiman, Christopher A.
Hankinson, Susan E.
Henderson, Brian E.
Hoover, Robert
Hunter, David J.
Kaaks, Rudolf
Kolonel, Laurence
Kraft, Peter
LeMarchand, Loic
Lund, Eiliv
Palli, Domenico
Peeters, Petra H. M.
Riboli, Elio
Stram, Daniel O.
Thun, Michael
Tjonneland, Anne
Trichopoulos, Dimitrios
Yeager, Meredith
BREAST CANCER RESEARCH, 2006, 8 (05)
[5] A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
David G Cox
Hélène Blanché
Celeste L Pearce
Eugenia E Calle
Graham A Colditz
Malcolm C Pike
Demetrius Albanes
Naomi E Allen
Pilar Amiano
Goran Berglund
Heiner Boeing
Julie Buring
Noel Burtt
Federico Canzian
Stephen Chanock
Françoise Clavel-Chapelon
Heather Spencer Feigelson
Matthew Freedman
Christopher A Haiman
Susan E Hankinson
Brian E Henderson
Robert Hoover
David J Hunter
Rudolf Kaaks
Laurence Kolonel
Peter Kraft
Loic LeMarchand
Eiliv Lund
Domenico Palli
Petra HM Peeters
Elio Riboli
Daniel O Stram
Michael Thun
Anne Tjonneland
Dimitrios Trichopoulos
Meredith Yeager
Breast Cancer Research, 8
[6] CYP17 genetic variation and risk of breast and prostate cancer from the national Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
Setiawan, Veronica Wendy
Schumacher, Fredrick R.
Haiman, Christopher A.
Stram, Daniel O.
Albanes, Demetrius
Altshuler, David
Berglund, Gran
Buring, Julie
Calle, Eugenia E.
Clavel-Chapelon, Françoise
Cox, David G.
Gaziano, J. Michael
Hankinson, Susan E.
Hayes, Richard B.
Henderson, Brian E.
Hirschhorn, Joel
Hoover, Robert
Hunter, David J.
Kaaks, Rudolf
Kolonel, Laurence N.
Kraft, Peter
Ma, Jing
Le Marchand, Loic
Linseisen, Jakob
Lund, Eiliv
Navarro, Carmen
Overvad, Kim
Palli, Domenico
Peeters, Petra H. M.
Pike, Malcolm C.
Riboli, Elio
Stampfer, Meir J.
Thun, Michael J.
Travis, Ruth
Trichopoulos, Dimitrios
Yeager, Meredith
Ziegler, Regina G.
Feigelson, Heather Spencer
Chanock, Stephen J.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (11) : 2237 - 2246
[7] Genetic Variation in the Vitamin D Pathway in Relation to Risk of Prostate Cancer-Results from the Breast and Prostate Cancer Cohort Consortium
Mondul, Alison M.
Shui, Irene M.
Yu, Kai
Travis, Ruth C.
Stevens, Victoria L.
Campa, Daniele
Schumacher, Frederick R.
Ziegler, Regina G.
Bueno-de-Mesquita, H. Bas
Berndt, Sonja
Crawford, E. D.
Gapstur, Susan M.
Gaziano, J. Michael
Giovannucci, Edward
Haiman, Christopher A.
Henderson, Brian E.
Hunter, David J.
Johansson, Mattias
Key, Timothy J.
Le Marchand, Loic
Lindstroem, Sara
McCullough, Marjorie L.
Navarro, Carmen
Overvad, Kim
Palli, Domenico
Purdue, Mark
Stampfer, Meir J.
Weinstein, Stephanie J.
Willett, Walter C.
Yeager, Meredith
Chanock, Stephen J.
Trichopoulos, Dimitrios
Kolonel, Laurence N.
Kraft, Peter
Albanes, Demetrius
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2013, 22 (04) : 688 - 696
[8] CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
Travis, Ruth C.
Schumacher, Fredrick
Hirschhorn, Joel N.
Kraft, Peter
Allen, Naomi E.
Albanes, Demetrius
Berglund, Goran
Berndt, Sonja I.
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Calle, Eugenia E.
Chanock, Stephen
Dunning, Alison M.
Hayes, Richard
Feigelson, Heather Spencer
Gaziano, J. Michael
Giovannucci, Edward
Haiman, Christopher A.
Henderson, Brian E.
Kaaks, Rudolf
Kolonel, Laurence N.
Ma, Jing
Rodriguez, Laudina
Riboli, Elio
Stampfer, Meir
Stram, Daniel O.
Thun, Michael J.
Tjonneland, Anne
Trichopoulos, Dimitrios
Vineis, Paolo
Virtamo, Jarmo
Le Marchand, Loic
Hunter, David J.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2009, 18 (10) : 2734 - 2744
[9] Interactions Between Genetic Variants and Breast Cancer Risk Factors in the Breast and Prostate Cancer Cohort Consortium
Campa, Daniele
Kaaks, Rudolf
Le Marchand, Loic
Haiman, Christopher A.
Travis, Ruth C.
Berg, Christine D.
Buring, Julie E.
Chanock, Stephen J.
Diver, W. Ryan
Dostal, Lucie
Fournier, Agnes
Hankinson, Susan E.
Henderson, Brian E.
Hoover, Robert N.
Isaacs, Claudine
Johansson, Mattias
Kolonel, Laurence N.
Kraft, Peter
Lee, I-Min
McCarty, Catherine A.
Overvad, Kim
Panico, Salvatore
Peeters, Petra H. M.
Riboli, Elio
Jose Sanchez, Maria
Schumacher, Fredrick R.
Skeie, Guri
Stram, Daniel O.
Thun, Michael J.
Trichopoulos, Dimitrios
Zhang, Shumin
Ziegler, Regina G.
Hunter, David J.
Lindstroem, Sara
Canzian, Federico
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2011, 103 (16): : 1252 - 1263
[10] Common Genetic Variants in Prostate Cancer Risk Prediction-Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
Lindstroem, Sara
Schumacher, Fredrick R.
Cox, David
Travis, Ruth C.
Albanes, Demetrius
Allen, Naomi E.
Andriole, Gerald
Berndt, Sonja I.
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Crawford, E. David
Diver, W. Ryan
Gaziano, J. Michael
Giles, Graham G.
Giovannucci, Edward
Gonzalez, Carlos A.
Henderson, Brian
Hunter, David J.
Johansson, Mattias
Kolonel, Laurence N.
Ma, Jing
Le Marchand, Loic
Pala, Valeria
Stampfer, Meir
Stram, Daniel O.
Thun, Michael J.
Tjonneland, Anne
Trichopoulos, Dimitrios
Virtamo, Jarmo
Weinstein, Stephanie J.
Willett, Walter C.
Yeager, Meredith
Hayes, Richard B.
Severi, Gianluca
Haiman, Christopher A.
Chanock, Stephen J.
Kraft, Peter
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2012, 21 (03) : 437 - 444

← 1 2 3 4 5 →