Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer

被引：56

作者：

Hoffmann, Thomas J. ^{[1
,2
]}

Passarelli, Michael N. ^{[1
]}

Graff, Rebecca E. ^{[1
]}

Emami, Nima C. ^{[1
]}

Sakoda, Lori C. ^{[3
]}

Jorgenson, Eric ^{[3
]}

Habel, Laurel A. ^{[3
]}

Shan, Jun ^{[3
]}

Ranatunga, Dilrini K. ^{[3
]}

Quesenberry, Charles P. ^{[3
]}

Chao, Chun R. ^{[4
]}

Ghai, Nirupa R. ^{[4
]}

Aaronson, David ^{[5
]}

Presti, Joseph ^{[5
]}

Nordstrom, Tobias ^{[6
]}

Wang, Zhaoming ^{[7
]}

Berndt, Sonja I. ^{[7
]}

Chanock, Stephen J. ^{[7
]}

Mosley, Jonathan D. ^{[8
]}

Klein, Robert J. ^{[9
,10
,11
,12
,13
,14
]}

Middha, Mridu ^{[9
,10
,11
,12
,13
,14
]}

Lilja, Hans ^{[10
,11
,12
,13
,14
]}

Melander, Olle ^{[15
]}

Kvale, Mark N. ^{[2
]}

Kwok, Pui-Yan ^{[2
]}

Schaefer, Catherine ^{[3
]}

Risch, Neil ^{[1
,2
,3
]}

Van Den Eeden, Stephen K. ^{[3
,16
]}

Witte, John S. ^{[1
,2
,16
]}

机构：

[1] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[3] Kaiser Permanente, Div Res, Oakland, CA 94612 USA

[4] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA

[5] Kaiser Oakland Med Ctr, Dept Urol, Oakland, CA 94612 USA

[6] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden

[7] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20814 USA

[8] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA

[9] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

[10] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA

[12] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[13] Univ Oxford, Nuffield Dept Surg Sci, Oxford OX3 7LD, England

[14] Lund Univ, Dept Translat Med, S-20502 Malmo, Sweden

[15] Lund Univ, Dept Clin Sci, S-20502 Malmo, Sweden

[16] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

GENETIC EPIDEMIOLOGY RESEARCH; SUSCEPTIBILITY LOCI; RANDOMIZED PROSTATE; SEQUENCE VARIANTS; ADULT HEALTH; SERUM-LEVELS; BASE-LINE; PSA; RISK; POLYMORPHISMS;

D O I：

10.1038/ncomms14248

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 x 10(-8)) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.

引用

页数：11

共 83 条

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Clapp, Jonathan D. ;

Rathmell, Joshua M. ;

Riley, Thomas L. ;

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Wang, Zhaoming ;

Yeager, Meredith ;

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Albanes, Demetrius ;

Amundadottir, Laufey ;

Andriole, Gerald ;

Freeman, Laura Beane ;

Campa, Daniele ;

Cancel-Tassin, Geraldine ;

Canzian, Federico ;

Cornu, Jean-Nicolas ;

Cussenot, Olivier ;

Diver, W. Ryan ;

Gapstur, Susan M. ;

Gronberg, Henrik ;

Haiman, Christopher A. ;

Henderson, Brian ;

Hutchinson, Amy ;

Hunter, David J. ;

Key, Timothy J. ;

Kolb, Suzanne ;

Koutros, Stella ;

Kraft, Peter ;

Le Marchand, Loic ;

Lindstroem, Sara ;

Machiela, Mitchell J. ;

Ostrander, Elaine A. ;

Riboli, Elio ;

Schumacher, Fred ;

Siddiq, Afshan ;

Stanford, Janet L. ;

Stevens, Victoria L. ;

Travis, Ruth C. ;

Tsilidis, Konstantinos K. ;

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← 1 2 3 4 5 6 7 8 9 →

共 83 条

[1] FGF signaling in prostate tumorigenesis - New insights into epithelial-stromal interactions [J].

Abate-Shen, Cory ;

Shen, Michael M. .

CANCER CELL, 2007, 12 (06) :495-497

[2] A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease [J].

Al Olama, Ali Amin ;

Kote-Jarai, Zsofia ;

Schumacher, Fredrick R. ;

Wiklund, Fredrik ;

Berndt, Sonja I. ;

Benlloch, Sara ;

Giles, Graham G. ;

Severi, Gianluca ;

Neal, David E. ;

Hamdy, Freddie C. ;

Donovan, Jenny L. ;

Hunter, David J. ;

Henderson, Brian E. ;

Thun, Michael J. ;

Gaziano, Michael ;

Giovannucci, Edward L. ;

Siddiq, Afshan ;

Travis, Ruth C. ;

Cox, David G. ;

Canzian, Federico ;

Riboli, Elio ;

Key, Timothy J. ;

Andriole, Gerald ;

Albanes, Demetrius ;

Hayes, Richard B. ;

Schleutker, Johanna ;

Auvinen, Anssi ;

Tammela, Teuvo L. J. ;

Weischer, Maren ;

Stanford, Janet L. ;

Ostrander, Elaine A. ;

Cybulski, Cezary ;

Lubinski, Jan ;

Thibodeau, Stephen N. ;

Schaid, Daniel J. ;

Sorensen, Karina D. ;

Batra, Jyotsna ;

Clements, Judith A. ;

Chambers, Suzanne ;

Aitken, Joanne ;

Gardiner, Robert A. ;

Maier, Christiane ;

Vogel, Walther ;

Doerk, Thilo ;

Brenner, Hermann ;

Habuchi, Tomonori ;

Ingles, Sue ;

John, Esther M. ;

Dickinson, Joanne L. ;

Cannon-Albright, Lisa .

HUMAN MOLECULAR GENETICS, 2013, 22 (02) :408-415

[3] Hundreds of variants clustered in genomic loci and biological pathways affect human height [J].

Allen, Hana Lango ;

Estrada, Karol ;

Lettre, Guillaume ;

Berndt, Sonja I. ;

Weedon, Michael N. ;

Rivadeneira, Fernando ;

Willer, Cristen J. ;

Jackson, Anne U. ;

Vedantam, Sailaja ;

Raychaudhuri, Soumya ;

Ferreira, Teresa ;

Wood, Andrew R. ;

Weyant, Robert J. ;

Segre, Ayellet V. ;

Speliotes, Elizabeth K. ;

Wheeler, Eleanor ;

Soranzo, Nicole ;

Park, Ju-Hyun ;

Yang, Jian ;

Gudbjartsson, Daniel ;

Heard-Costa, Nancy L. ;

Randall, Joshua C. ;

Qi, Lu ;

Smith, Albert Vernon ;

Maegi, Reedik ;

Pastinen, Tomi ;

Liang, Liming ;

Heid, Iris M. ;

Luan, Jian'an ;

Thorleifsson, Gudmar ;

Winkler, Thomas W. ;

Goddard, Michael E. ;

Lo, Ken Sin ;

Palmer, Cameron ;

Workalemahu, Tsegaselassie ;

Aulchenko, Yurii S. ;

Johansson, Asa ;

Zillikens, M. Carola ;

Feitosa, Mary F. ;

Esko, Tonu ;

Johnson, Toby ;

Ketkar, Shamika ;

Kraft, Peter ;

Mangino, Massimo ;

Prokopenko, Inga ;

Absher, Devin ;

Albrecht, Eva ;

Ernst, Florian ;

Glazer, Nicole L. ;

Hayward, Caroline .

NATURE, 2010, 467 (7317) :832-838

[4] Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up [J].

Andriole, Gerald L. ;

Crawford, E. David ;

Grubb, Robert L., III ;

Buys, Saundra S. ;

Chia, David ;

Church, Timothy R. ;

Fouad, Mona N. ;

Isaacs, Claudine ;

Kvale, Paul A. ;

Reding, Douglas J. ;

Weissfeld, Joel L. ;

Yokochi, Lance A. ;

O'Brien, Barbara ;

Ragard, Lawrence R. ;

Clapp, Jonathan D. ;

Rathmell, Joshua M. ;

Riley, Thomas L. ;

Hsing, Ann W. ;

Izmirlian, Grant ;

Pinsky, Paul F. ;

Kramer, Barnett S. ;

Miller, Anthony B. ;

Gohagan, John K. ;

Prorok, Philip C. .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2012, 104 (02) :125-132

[5] Mortality Results from a Randomized Prostate-Cancer Screening Trial [J].

Andriole, Gerald L. ;

Grubb, Robert L., III ;

Buys, Saundra S. ;

Chia, David ;

Church, Timothy R. ;

Fouad, Mona N. ;

Gelmann, Edward P. ;

Kvale, Paul A. ;

Reding, Douglas J. ;

Weissfeld, Joel L. ;

Yokochi, Lance A. ;

Crawford, E. David ;

O'Brien, Barbara ;

Clapp, Jonathan D. ;

Rathmell, Joshua M. ;

Riley, Thomas L. ;

Hayes, Richard B. ;

Kramer, Barnett S. ;

Izmirlian, Grant ;

Miller, Anthony B. ;

Pinsky, Paul F. ;

Prorok, Philip C. ;

Gohagan, John K. ;

Berg, Christine D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (13) :1310-1319

[6] Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort [J].

Banda, Yambazi ;

Kvale, Mark N. ;

Hoffmann, Thomas J. ;

Hesselson, Stephanie E. ;

Ranatunga, Dilrini ;

Tang, Hua ;

Sabatti, Chiara ;

Croen, Lisa A. ;

Dispensa, Brad P. ;

Henderson, Mary ;

Iribarren, Carlos ;

Jorgenson, Eric ;

Kushi, Lawrence H. ;

Ludwig, Dana ;

Olberg, Diane ;

Quesenberry, Charles P., Jr. ;

Rowell, Sarah ;

Sadler, Marianne ;

Sakoda, Lori C. ;

Sciortino, Stanley ;

Shen, Ling ;

Smethurst, David ;

Somkin, Carol P. ;

Van Den Eeden, Stephen K. ;

Walter, Lawrence ;

Whitmer, Rachel A. ;

Kwok, Pui-Yan ;

Schaefer, Catherine ;

Risch, Neil .

GENETICS, 2015, 200 (04) :1285-+

[7] Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins [J].

Bansal, A ;

Murray, DK ;

Wu, JT ;

Stephenson, RA ;

Middleton, RG ;

Meikle, AW .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (03) :1272-1276

[8] Genome-wide association study identifies three new melanoma susceptibility loci [J].

Barrett, Jennifer H. ;

Iles, Mark M. ;

Harland, Mark ;

Taylor, John C. ;

Aitken, Joanne F. ;

Andresen, Per Arne ;

Akslen, Lars A. ;

Armstrong, Bruce K. ;

Avril, Marie-Francoise ;

Azizi, Esther ;

Bakker, Bert ;

Bergman, Wilma ;

Bianchi-Scarra, Giovanna ;

Bressac-de Paillerets, Brigitte ;

Calista, Donato ;

Cannon-Albright, Lisa A. ;

Corda, Eve ;

Cust, Anne E. ;

Debniak, Tadeusz ;

Duffy, David ;

Dunning, Alison M. ;

Easton, Douglas F. ;

Friedman, Eitan ;

Galan, Pilar ;

Ghiorzo, Paola ;

Giles, Graham G. ;

Hansson, Johan ;

Hocevar, Marko ;

Hoeiom, Veronica ;

Hopper, John L. ;

Ingvar, Christian ;

Janssen, Bart ;

Jenkins, Mark A. ;

Joensson, Goeran ;

Kefford, Richard F. ;

Landi, Giorgio ;

Landi, Maria Teresa ;

Lang, Julie ;

Lubinski, Jan ;

Mackie, Rona ;

Malvehy, Josep ;

Martin, Nicholas G. ;

Molven, Anders ;

Montgomery, Grant W. ;

van Nieuwpoort, Frans A. ;

Novakovic, Srdjan ;

Olsson, Hakan ;

Pastorino, Lorenza ;

Puig, Susana ;

Puig-Butille, Joan Anton .

NATURE GENETICS, 2011, 43 (11) :1108-U98

[9] Two susceptibility loci identified for prostate cancer aggressiveness [J].

Berndt, Sonja I. ;

Wang, Zhaoming ;

Yeager, Meredith ;

Alavanja, Michael C. ;

Albanes, Demetrius ;

Amundadottir, Laufey ;

Andriole, Gerald ;

Freeman, Laura Beane ;

Campa, Daniele ;

Cancel-Tassin, Geraldine ;

Canzian, Federico ;

Cornu, Jean-Nicolas ;

Cussenot, Olivier ;

Diver, W. Ryan ;

Gapstur, Susan M. ;

Gronberg, Henrik ;

Haiman, Christopher A. ;

Henderson, Brian ;

Hutchinson, Amy ;

Hunter, David J. ;

Key, Timothy J. ;

Kolb, Suzanne ;

Koutros, Stella ;

Kraft, Peter ;

Le Marchand, Loic ;

Lindstroem, Sara ;

Machiela, Mitchell J. ;

Ostrander, Elaine A. ;

Riboli, Elio ;

Schumacher, Fred ;

Siddiq, Afshan ;

Stanford, Janet L. ;

Stevens, Victoria L. ;

Travis, Ruth C. ;

Tsilidis, Konstantinos K. ;

Virtamo, Jarmo ;

Weinstein, Stephanie ;

Wilkund, Fredrik ;

Xu, Jianfeng ;

Zheng, S. Lilly ;

Yu, Kai ;

Wheeler, William ;

Zhang, Han ;

Consortium, African Ancestry Prostate Canc G. W. A. S. ;

Sampson, Joshua ;

Black, Amanda ;

Jacobs, Kevin ;

Hoover, Robert N. ;

Tucker, Margaret ;

Chanock, Stephen J. .

NATURE COMMUNICATIONS, 2015, 6

[10] Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture [J].

Berndt, Sonja I. ;

Gustafsson, Stefan ;

Maegi, Reedik ;

Ganna, Andrea ;

Wheeler, Eleanor ;

Feitosa, Mary F. ;

Justice, Anne E. ;

Monda, Keri L. ;

Croteau-Chonka, Damien C. ;

Day, Felix R. ;

Esko, Tonu ;

Fall, Tove ;

Ferreira, Teresa ;

Gentilini, Davide ;

Jackson, Anne U. ;

Luan, Jian'an ;

Randall, Joshua C. ;

Vedantam, Sailaja ;

Willer, Cristen J. ;

Winkler, Thomas W. ;

Wood, Andrew R. ;

Workalemahu, Tsegaselassie ;

Hu, Yi-Juan ;

Lee, Sang Hong ;

Liang, Liming ;

Lin, Dan-Yu ;

Min, Josine L. ;

Neale, Benjamin M. ;

Thorleifsson, Gudmar ;

Yang, Jian ;

Albrecht, Eva ;

Amin, Najaf ;

Bragg-Gresham, Jennifer L. ;

Cadby, Gemma ;

den Heijer, Martin ;

Eklund, Niina ;

Fischer, Krista ;

Goel, Anuj ;

Hottenga, Jouke-Jan ;

Huffman, Jennifer E. ;

Jarick, Ivonne ;

Johansson, Asa ;

Johnson, Toby ;

Kanoni, Stavroula ;

Kleber, Marcus E. ;

Koenig, Inke R. ;

Kristiansson, Kati ;

Kutalik, Zoltn ;

Lamina, Claudia ;

Lecoeur, Cecile .

NATURE GENETICS, 2013, 45 (05) :501-U69

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