Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer

被引：65

作者：

Wang, Meilin ^{[1
,2
,3
]}

Takahashi, Atsushi ^{[4
]}

Liu, Fang ^{[5
]}

Ye, Dingwei ^{[6
]}

Ding, Qiang ^{[5
]}

Qin, Chao ^{[7
]}

Yin, Changjun ^{[7
]}

Zhang, Zhengdong ^{[2
]}

Matsuda, Koichi ^{[8
]}

Kubo, Michiaki ^{[9
]}

Na, Rong ^{[5
]}

Lin, Xiaoling ^{[5
]}

Jiang, Haowen ^{[5
]}

Ren, Shancheng ^{[10
]}

Sun, Jielin ^{[3
]}

Zheng, S. Lilly ^{[3
,11
]}

Le Marchand, Loic ^{[12
]}

Isaacs, William B. ^{[13
]}

Mo, Zengnan ^{[14
]}

Haiman, Christopher A. ^{[15
]}

Sun, Yinghao ^{[10
]}

Nakagawa, Hidewaki ^{[16
]}

Xu, Jianfeng ^{[5
,11
]}

机构：

[1] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Dept Mol & Genet Toxicol, Key Lab Modern Toxicol, Minist Educ,Sch Publ Hlth, Nanjing 211166, Jiangsu, Peoples R China

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

[4] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan

[5] Fudan Univ, Huashan Hosp, Fudan Inst Urol, Shanghai 200040, Peoples R China

[6] Fudan Univ, Dept Urol, Shanghai Canc Ctr, Shanghai Med Coll, Shanghai 200032, Peoples R China

[7] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Jiangsu, Peoples R China

[8] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1088639, Japan

[9] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa 2300045, Japan

[10] Second Mil Med Univ, Shanghai Changhai Hosp, Dept Urol, Shanghai 200433, Peoples R China

[11] NorthShore Univ HealthSyst, Program Personalized Canc Care, Evanston, IL 60201 USA

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

[13] Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA

[14] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning 530021, Guangxi, Peoples R China

[15] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA

[16] RIKEN Ctr Integrat Med Sci, Lab Genome Sequencing Anal, Tokyo 1088639, Japan

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; RISK; POLYMORPHISMS; JAPANESE; BETA; RMST; SNPS;

D O I：

10.1038/ncomms9469

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：

Genome-wide association studies (GWAS) have identified similar to 100 genetic loci associated with prostate cancer risk. Less than a dozen of these loci were initially identified from GWAS in two Asian populations, likely because of smaller sample sizes of these individual GWAS in Asians. Here, we conduct a large-scale meta-analysis of two GWAS from the Japanese population (1,583 cases and 3,386 controls) and the Chinese population (1,417 cases and 1,008 controls), followed by replication in three independent sample sets. We identify two independent susceptibility loci for prostate cancer at 11p15.4 (rs12791447, P = 3.59 x 10(-8); PPFIBP2) and 14q23.2 (rs58262369, P = 6.05 x 10(-10); ESR2). The mRNA levels of PPFIBP2 and ESR2 are differentially expressed in prostate tumours and paired normal tissues. Our study adds two new loci to the limited number of prostate cancer risk-associated variants in Asians and provides important insight into potential biological mechanisms of prostate cancer.

引用

页数：7

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