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

Meilin Wang, Atsushi Takahashi, Fang Liu, Dingwei Ye, Qiang Ding, Chao Qin, Changjun Yin, Zhengdong Zhang, Koichi Matsuda, Michiaki Kubo, Rong Na, Xiaoling Lin, Haowen Jiang, Shancheng Ren, Jielin Sun, S. Lilly Zheng, Loic Le Marchand, William B. Isaacs, Zengnan Mo, Christopher A. Haiman, Yinghao Sun (), Hidewaki Nakagawa () and Jianfeng Xu ()
Additional contact information
Meilin Wang: State Key Laboratory of Reproductive Medicine, Nanjing Medical University
Atsushi Takahashi: Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences
Fang Liu: Fudan Institute of Urology, Huashan Hospital, Fudan University
Dingwei Ye: Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University
Qiang Ding: Fudan Institute of Urology, Huashan Hospital, Fudan University
Chao Qin: The First Affiliated Hospital of Nanjing Medical University
Changjun Yin: The First Affiliated Hospital of Nanjing Medical University
Zhengdong Zhang: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University
Koichi Matsuda: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo
Michiaki Kubo: Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences
Rong Na: Fudan Institute of Urology, Huashan Hospital, Fudan University
Xiaoling Lin: Fudan Institute of Urology, Huashan Hospital, Fudan University
Haowen Jiang: Fudan Institute of Urology, Huashan Hospital, Fudan University
Shancheng Ren: Shanghai Changhai Hospital, Second Military Medical University
Jielin Sun: Center for Cancer Genomics, Wake Forest University School of Medicine
S. Lilly Zheng: Center for Cancer Genomics, Wake Forest University School of Medicine
Loic Le Marchand: University of Hawaii Cancer Center
William B. Isaacs: James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine
Zengnan Mo: Center for Genomic and Personalized Medicine, Guangxi Medical University
Christopher A. Haiman: Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
Yinghao Sun: Shanghai Changhai Hospital, Second Military Medical University
Hidewaki Nakagawa: Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences
Jianfeng Xu: Fudan Institute of Urology, Huashan Hospital, Fudan University

Nature Communications, 2015, vol. 6, issue 1, 1-7

Abstract: Abstract Genome-wide association studies (GWAS) have identified ∼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 × 10−8; PPFIBP2) and 14q23.2 (rs58262369, P=6.05 × 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.

Date: 2015
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DOI: 10.1038/ncomms9469

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