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

Ryo Takata (), Atsushi Takahashi, Masashi Fujita, Yukihide Momozawa, Edward J. Saunders, Hiroki Yamada, Kazuhiro Maejima, Kaoru Nakano, Yuichiro Nishida, Asahi Hishida, Keitaro Matsuo, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Makoto Sasaki, Atsushi Shimizu, Kozo Tanno, Naoko Minegishi, Kichiya Suzuki, Koichi Matsuda, Michiaki Kubo, Johji Inazawa, Shin Egawa, Christopher A. Haiman, Osamu Ogawa, Wataru Obara, Yoichiro Kamatani, Shusuke Akamatsu () and Hidewaki Nakagawa ()
Additional contact information
Ryo Takata: Iwate Medical University
Atsushi Takahashi: RIKEN Center for Integrative Medical Sciences
Masashi Fujita: RIKEN Center for Integrative Medical Sciences
Yukihide Momozawa: RIKEN Center for Integrative Medical Sciences
Edward J. Saunders: The Institute of Cancer Research
Hiroki Yamada: Jikei University School of Medicine
Kazuhiro Maejima: RIKEN Center for Integrative Medical Sciences
Kaoru Nakano: RIKEN Center for Integrative Medical Sciences
Yuichiro Nishida: Saga University
Asahi Hishida: Nagoya University Graduate School of Medicine
Keitaro Matsuo: Aichi Cancer Center Research Institute
Kenji Wakai: Nagoya University Graduate School of Medicine
Taiki Yamaji: National Cancer Center
Norie Sawada: National Cancer Center
Motoki Iwasaki: National Cancer Center
Shoichiro Tsugane: National Cancer Center
Makoto Sasaki: Iwate Medical University
Atsushi Shimizu: Iwate Medical University
Kozo Tanno: Iwate Medical University
Naoko Minegishi: Tohoku University
Kichiya Suzuki: Tohoku University
Koichi Matsuda: The University of Tokyo
Michiaki Kubo: RIKEN Center for Integrative Medical Sciences
Johji Inazawa: Tokyo Medical and Dental University
Shin Egawa: Jikei University School of Medicine
Christopher A. Haiman: University of Southern California
Osamu Ogawa: Kyoto University Graduate School of Medicine
Wataru Obara: Iwate Medical University
Yoichiro Kamatani: RIKEN Center for Integrative Medical Sciences
Shusuke Akamatsu: RIKEN Center for Integrative Medical Sciences
Hidewaki Nakagawa: RIKEN Center for Integrative Medical Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12267-6

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