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Nat Commun. 2019 Sep 27;10(1):4422. doi: 10.1038/s41467-019-12267-6.

12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population.

Author information

1
Department of Urology, Iwate Medical University, Morioka, 020-8505, Japan. rtakata@iwate-med.ac.jp.
2
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. rtakata@iwate-med.ac.jp.
3
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
4
Department of Genomic Medicine, National Cerebral and Cardiovascular Center Research Institute, Suita, 564-8565, Japan.
5
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
6
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
7
The Institute of Cancer Research, London, SW7 3RP, UK.
8
Department of Urology, Jikei University School of Medicine, 105-8461, Tokyo, Japan.
9
Department of Preventive Medicine, Faculty of Medicine, Saga University, 840-8502, Saga, Japan.
10
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
11
Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, 464-8681, Nagoya, Japan.
12
Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
13
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, 104-0045, Japan.
14
Center for Public Health Sciences, National Cancer Center, 104-0045, Tokyo, Japan.
15
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Yahaba, 028-3694, Japan.
16
Tohoku Medical Megabank Organization, Tohoku University, Sendai, 980-8573, Japan.
17
Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 108-8639, Tokyo, Japan.
18
RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
19
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
20
Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033, USA.
21
Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
22
Department of Urology, Iwate Medical University, Morioka, 020-8505, Japan.
23
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. akamats@kuhp.kyoto-u.ac.jp.
24
Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan. akamats@kuhp.kyoto-u.ac.jp.
25
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. hidewaki@riken.jp.

Abstract

Genome-wide association studies (GWAS) have identified ~170 genetic loci associated with prostate cancer (PCa) risk, but most of them were identified in European populations. We here performed a GWAS and replication study using a large Japanese cohort (9,906 cases and 83,943 male controls) to identify novel susceptibility loci associated with PCa risk. We found 12 novel loci for PCa including rs1125927 (TMEM17, P = 3.95 × 10-16), rs73862213 (GATA2, P = 5.87 × 10-23), rs77911174 (ZMIZ1, P = 5.28 × 10-20), and rs138708 (SUN2, P = 1.13 × 10-15), seven of which had crucially low minor allele frequency in European population. Furthermore, we stratified the polygenic risk for Japanese PCa patients by using 82 SNPs, which were significantly associated with Japanese PCa risk in our study, and found that early onset cases and cases with family history of PCa were enriched in the genetically high-risk population. Our study provides important insight into genetic mechanisms of PCa and facilitates PCa risk stratification in Japanese population.

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