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Nat Commun. 2015 Oct 7;6:8469. doi: 10.1038/ncomms9469.

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

Author information

1
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
2
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.
3
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
4
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
5
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
6
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
7
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
8
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
9
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
10
Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
11
Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois 60201, USA.
12
Department of Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawai 96813, USA.
13
Department of Urology, James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
14
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
15
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
16
Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan.

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.

PMID:
26443449
PMCID:
PMC4633711
DOI:
10.1038/ncomms9469
[Indexed for MEDLINE]
Free PMC Article

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