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

被引：100

作者：

Al Olama, Ali Amin ^{[2
]}

Kote-Jarai, Zsofia

Schumacher, Fredrick R. ^{[3
]}

Wiklund, Fredrik ^{[4
]}

Berndt, Sonja I. ^{[5
,6
]}

Benlloch, Sara ^{[2
]}

Giles, Graham G. ^{[7
,8
]}

Severi, Gianluca ^{[7
,8
]}

Neal, David E. ^{[9
,10
]}

Hamdy, Freddie C. ^{[11
,13
]}

Donovan, Jenny L. ^{[14
]}

Hunter, David J. ^{[15
]}

Henderson, Brian E. ^{[3
]}

Thun, Michael J. ^{[16
]}

Gaziano, Michael ^{[17
,18
,19
]}

Giovannucci, Edward L.

Siddiq, Afshan ^{[20
]}

Travis, Ruth C. ^{[12
]}

Cox, David G. ^{[21
,22
]}

Canzian, Federico ^{[23
]}

Riboli, Elio ^{[21
]}

Key, Timothy J. ^{[12
]}

Andriole, Gerald ^{[26
]}

Albanes, Demetrius ^{[5
]}

Hayes, Richard B. ^{[27
]}

Schleutker, Johanna ^{[28
,33
]}

Auvinen, Anssi ^{[30
]}

Tammela, Teuvo L. J. ^{[31
,32
]}

Weischer, Maren ^{[34
]}

Stanford, Janet L. ^{[36
,37
]}

Ostrander, Elaine A. ^{[38
]}

Cybulski, Cezary ^{[39
]}

Lubinski, Jan ^{[39
]}

Thibodeau, Stephen N. ^{[40
]}

Schaid, Daniel J. ^{[40
]}

Sorensen, Karina D. ^{[41
]}

Batra, Jyotsna ^{[43
]}

Clements, Judith A. ^{[43
]}

Chambers, Suzanne ^{[44
,45
,46
]}

Aitken, Joanne ^{[45
]}

Gardiner, Robert A. ^{[46
]}

Maier, Christiane ^{[47
,48
]}

Vogel, Walther ^{[48
]}

Doerk, Thilo ^{[49
]}

Brenner, Hermann ^{[24
]}

Habuchi, Tomonori ^{[50
]}

Ingles, Sue ^{[3
]}

John, Esther M. ^{[51
,52
,53
]}

Dickinson, Joanne L. ^{[54
]}

Cannon-Albright, Lisa ^{[55
,56
]}

机构：

[1] Inst Canc Res, Oncogenet Team, Sutton SM2 5NG, Surrey, England

[2] Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge CB1 8RN, England

[3] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA

[4] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

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

[6] NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH, Gaithersburg, MD USA

[7] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia

[8] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia

[9] Univ Cambridge, Addenbrookes Hosp, Cambridge CB2 2QQ, England

[10] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 2QQ, England

[11] Univ Oxford, Nuffield Dept Surg, Oxford, England

[12] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[13] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford OX3 9DU, England

[14] Univ Bristol, Sch Social & Community Med, Bristol BS8 2PS, Avon, England

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

[16] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA

[17] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA 02114 USA

[18] Boston Vet Affairs Healthcare Syst, GRECC, Boston, MA 02114 USA

[19] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02215 USA

[20] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London SW7 2AZ, England

[21] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England

[22] INSERM, U1052, Lyon Canc Res Ctr, F-69008 Lyon, France

[23] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany

[24] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

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

[26] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA

[27] NYU Canc Inst, NYU Langone Med Ctr, Div Epidemiol, Dept Environm Med, New York, NY 10016 USA

[28] Univ Tampere, Inst Biomed Technol BioMediTech, FIN-33101 Tampere, Finland

[29] Tampere Univ Hosp, Dept Pathol, Ctr Lab Med, Tampere, Finland

[30] Tampere Univ Hosp, Dept Epidemiol, Sch Hlth Sci, Tampere, Finland

[31] Tampere Univ Hosp, Dept Urol, Tampere, Finland

[32] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland

[33] Univ Turku, Dept Med Biochem & Genet, Turku, Finland

[34] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark

[35] Copenhagen Univ Hosp, Herlev Hosp, Dept Urol, DK-2730 Herlev, Denmark

[36] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[37] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[38] NHGRI, NIH, Bethesda, MD 20892 USA

[39] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland

[40] Mayo Clin, Rochester, MN USA

[41] Aarhus Univ Hosp, Dept Mol Med, Skejby, Denmark

[42] Aarhus Univ Hosp, Dept Urol, Skejby, Denmark

[43] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr Qld, Brisbane, Qld 4001, Australia

[44] Griffith Univ, Griffith Hlth Inst, Gold Coast, Qld, Australia

[45] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia

[46] Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia

[47] Univ Hosp Ulm, Dept Urol, Ulm, Germany

[48] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany

[49] Hannover Med Sch, D-3000 Hannover, Germany

[50] Akita Univ, Grad Sch Med, Dept Urol, Akita 0108543, Japan

来源：

HUMAN MOLECULAR GENETICS | 2013年 / 22卷 / 02期

关键词：

GENES; EXPRESSION; VARIANTS; FAMILY; RISK;

D O I：

10.1093/hmg/dds425

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio 1.12 (95 confidence interval 1.031.21), P 1.4 10(8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

引用

页码：408 / 415

页数：8

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