Two susceptibility loci identified for prostate cancer aggressiveness

被引：73

作者：

Berndt, Sonja I. ^{[1
]}

Wang, Zhaoming ^{[1
,2
]}

Yeager, Meredith ^{[1
,2
]}

Alavanja, Michael C. ^{[1
]}

Albanes, Demetrius ^{[1
]}

Amundadottir, Laufey ^{[1
]}

Andriole, Gerald ^{[3
]}

Freeman, Laura Beane ^{[1
]}

Campa, Daniele ^{[4
]}

Cancel-Tassin, Geraldine ^{[5
]}

Canzian, Federico ^{[6
]}

Cornu, Jean-Nicolas ^{[1
]}

Cussenot, Olivier ^{[5
]}

Diver, W. Ryan ^{[7
]}

Gapstur, Susan M. ^{[7
]}

Gronberg, Henrik ^{[8
]}

Haiman, Christopher A. ^{[9
]}

Henderson, Brian ^{[9
]}

Hutchinson, Amy ^{[2
]}

Hunter, David J. ^{[10
]}

Key, Timothy J. ^{[11
]}

Kolb, Suzanne ^{[12
]}

Koutros, Stella ^{[1
]}

Kraft, Peter ^{[10
]}

Le Marchand, Loic ^{[13
]}

Lindstroem, Sara ^{[10
]}

Machiela, Mitchell J. ^{[1
]}

Ostrander, Elaine A. ^{[14
]}

Riboli, Elio ^{[15
]}

Schumacher, Fred ^{[9
]}

Siddiq, Afshan ^{[16
]}

Stanford, Janet L. ^{[12
,17
]}

Stevens, Victoria L. ^{[7
]}

Travis, Ruth C. ^{[11
]}

Tsilidis, Konstantinos K. ^{[18
]}

Virtamo, Jarmo ^{[19
]}

Weinstein, Stephanie ^{[1
]}

Wilkund, Fredrik ^{[8
]}

Xu, Jianfeng ^{[20
]}

Zheng, S. Lilly ^{[20
]}

Yu, Kai ^{[1
]}

Wheeler, William ^{[21
]}

Zhang, Han ^{[1
]}

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

Sampson, Joshua ^{[1
]}

Black, Amanda ^{[1
]}

Jacobs, Kevin ^{[1
]}

Hoover, Robert N. ^{[1
]}

Tucker, Margaret ^{[1
]}

Chanock, Stephen J. ^{[1
]}

机构：

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

[2] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA

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

[4] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[5] Univ Paris 06, AP HP, CeRePP, Paris, France

[6] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany

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

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

[9] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Preventat Med, Los Angeles, CA 90033 USA

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

[11] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford OX3 7BN, England

[12] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[13] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA

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

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

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

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

[18] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

[19] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland

[20] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Gen, Winston Salem, NC 27157 USA

[21] Informat Management Serv Inc, Rockville, MD 20852 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

GENOME-WIDE ASSOCIATION; LINKAGE SCAN; SEQUENCE VARIANTS; GLEASON SCORE; RISK; COHORT; METAANALYSIS; REPLICATION; PROGRESSION; PREDICTION;

D O I：

10.1038/ncomms7889

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：

Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P = 6.49 x 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P = 4.18 x 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P = 8.85 x 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P = 0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.

引用

页数：7

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