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; Jianfeng Xu

doi:10.1038/ncomms9469

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. HaimanYinghao Sun, Hidewaki Nakagawa, Jianfeng Xu

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Abstract

Genome-wide association studies (GWAS) have identified 1/4100 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.

Original language	English
Article number	8469
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9469
Publication status	Published - 07-10-2015

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Wang, M., Takahashi, A., Liu, F., Ye, D., Ding, Q., Qin, C., Yin, C., Zhang, Z., Matsuda, K., Kubo, M., Na, R., Lin, X., Jiang, H., Ren, S., Sun, J., Zheng, S. L., Marchand, L. L., Isaacs, W. B., Mo, Z., ... Xu, J. (2015). Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer. Nature communications, 6, [8469]. https://doi.org/10.1038/ncomms9469

Wang, Meilin ; Takahashi, Atsushi ; Liu, Fang ; Ye, Dingwei ; Ding, Qiang ; Qin, Chao ; Yin, Changjun ; Zhang, Zhengdong ; Matsuda, Koichi ; Kubo, Michiaki ; Na, Rong ; Lin, Xiaoling ; Jiang, Haowen ; Ren, Shancheng ; Sun, Jielin ; Zheng, S. Lilly ; Marchand, Loic Le ; Isaacs, William B. ; Mo, Zengnan ; Haiman, Christopher A. ; Sun, Yinghao ; Nakagawa, Hidewaki ; Xu, Jianfeng. / Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer. In: Nature communications. 2015 ; Vol. 6.

@article{08fde096d18f4d93a06d1c860374998b,

title = "Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer",

abstract = "Genome-wide association studies (GWAS) have identified 1/4100 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.",

author = "Meilin Wang and Atsushi Takahashi and Fang Liu and Dingwei Ye and Qiang Ding and Chao Qin and Changjun Yin and Zhengdong Zhang and Koichi Matsuda and Michiaki Kubo and Rong Na and Xiaoling Lin and Haowen Jiang and Shancheng Ren and Jielin Sun and Zheng, {S. Lilly} and Marchand, {Loic Le} and Isaacs, {William B.} and Zengnan Mo and Haiman, {Christopher A.} and Yinghao Sun and Hidewaki Nakagawa and Jianfeng Xu",

note = "Funding Information: This work was in part supported by grants from the Key Project of the National Science Foundation of China to J.X. (81130047), the National Key Basic Research Program Grant 973 of China to J.X. (2012CB518301), intramural grants from Fudan University to J.X., the National Science Foundation of China to F.L. (81202001), the National Science Foundation of China to X.L. (81202269), Shanghai Municipal Commission of Health and Family Planning to H.J. (XBR2013092) and Shanghai Municipal Education Commission to H.J. (14ZZ010). The BioBank Japan and Japanese GWAS were supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. The GWAS in the MEC was supported by grants CA164973 and HG004726 from the National Institutes of Health. This work was also partially supported by the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University HealthSystem to J.X.",

year = "2015",

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Wang, M, Takahashi, A, Liu, F, Ye, D, Ding, Q, Qin, C, Yin, C, Zhang, Z, Matsuda, K, Kubo, M, Na, R, Lin, X, Jiang, H, Ren, S, Sun, J, Zheng, SL, Marchand, LL, Isaacs, WB, Mo, Z, Haiman, CA, Sun, Y, Nakagawa, H & Xu, J 2015, 'Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer', Nature communications, vol. 6, 8469. https://doi.org/10.1038/ncomms9469

Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer. / Wang, Meilin; Takahashi, Atsushi; Liu, Fang; Ye, Dingwei; Ding, Qiang; Qin, Chao; Yin, Changjun; Zhang, Zhengdong; Matsuda, Koichi; Kubo, Michiaki; Na, Rong; Lin, Xiaoling; Jiang, Haowen; Ren, Shancheng; Sun, Jielin; Zheng, S. Lilly; Marchand, Loic Le; Isaacs, William B.; Mo, Zengnan; Haiman, Christopher A.; Sun, Yinghao; Nakagawa, Hidewaki; Xu, Jianfeng.

In: Nature communications, Vol. 6, 8469, 07.10.2015.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer

AU - Wang, Meilin

AU - Takahashi, Atsushi

AU - Liu, Fang

AU - Ye, Dingwei

AU - Ding, Qiang

AU - Qin, Chao

AU - Yin, Changjun

AU - Zhang, Zhengdong

AU - Matsuda, Koichi

AU - Kubo, Michiaki

AU - Na, Rong

AU - Lin, Xiaoling

AU - Jiang, Haowen

AU - Ren, Shancheng

AU - Sun, Jielin

AU - Zheng, S. Lilly

AU - Marchand, Loic Le

AU - Isaacs, William B.

AU - Mo, Zengnan

AU - Haiman, Christopher A.

AU - Sun, Yinghao

AU - Nakagawa, Hidewaki

AU - Xu, Jianfeng

N1 - Funding Information: This work was in part supported by grants from the Key Project of the National Science Foundation of China to J.X. (81130047), the National Key Basic Research Program Grant 973 of China to J.X. (2012CB518301), intramural grants from Fudan University to J.X., the National Science Foundation of China to F.L. (81202001), the National Science Foundation of China to X.L. (81202269), Shanghai Municipal Commission of Health and Family Planning to H.J. (XBR2013092) and Shanghai Municipal Education Commission to H.J. (14ZZ010). The BioBank Japan and Japanese GWAS were supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. The GWAS in the MEC was supported by grants CA164973 and HG004726 from the National Institutes of Health. This work was also partially supported by the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University HealthSystem to J.X.

PY - 2015/10/7

Y1 - 2015/10/7

N2 - Genome-wide association studies (GWAS) have identified 1/4100 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.

AB - Genome-wide association studies (GWAS) have identified 1/4100 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.

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U2 - 10.1038/ncomms9469

DO - 10.1038/ncomms9469

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VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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