title: Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer.
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.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Molecular and Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Molecular and Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Koichi
authors.identifier: http://orcid.org/0000-0001-7292-2686
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Na
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lin
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Shancheng
authors.initials: S
authors.lastname: Ren
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.|Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois 60201, USA.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawai 96813, USA.
authors.forename: Loic Le
authors.initials: LL
authors.lastname: Marchand
authors.affiliation: Department of Urology, James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan.
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.|Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois 60201, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D047629:Estrogen Receptor beta / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C559265:PPFIBP2 protein, human; D012333:RNA, Messenger