Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer

Hiromi Sakamoto; Kimio Yoshimura; Norihisa Saeki; Hitoshi Katai; Tadakazu Shimoda; Yoshihiro Matsuno; Daizo Saito; Haruhiko Sugimura; Fumihiko Tanioka; Shunji Kato; Norio Matsukura; Noriko Matsuda; Tsuneya Nakamura; Ichinosuke Hyodo; Tomohiro Nishina; Wataru Yasui; Hiroshi Hirose; Matsuhiko Hayashi; Emi Toshiro; Sumiko Ohnami; Akihiro Sekine; Yasunori Sato; Hirohiko Totsuka; Masataka Ando; Ryo Takemura; Yoriko Takahashi; Minoru Ohdaira; Kenichi Aoki; Izumi Honmyo; Suenori Chiku; Kazuhiko Aoyagi; Hiroki Sasaki; Shumpei Ohnami; Kazuyoshi Yanagihara; Kyong Ah Yoon; Myeong Cherl Kook; Yeon Su Lee; Sook Ryun Park; Chan Gyoo Kim; Il Ju Choi; Teruhiko Yoshida; Yusuke Nakamura; Setsuo Hirohashi

doi:10.1038/ng.152

Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer

Hiromi Sakamoto, Kimio Yoshimura, Norihisa Saeki, Hitoshi Katai, Tadakazu Shimoda, Yoshihiro Matsuno, Daizo Saito, Haruhiko Sugimura, Fumihiko Tanioka, Shunji Kato, Norio Matsukura, Noriko Matsuda, Tsuneya Nakamura, Ichinosuke Hyodo, Tomohiro Nishina, Wataru Yasui, Hiroshi Hirose, Matsuhiko Hayashi, Emi Toshiro, Sumiko OhnamiAkihiro Sekine, Yasunori Sato, Hirohiko Totsuka, Masataka Ando, Ryo Takemura, Yoriko Takahashi, Minoru Ohdaira, Kenichi Aoki, Izumi Honmyo, Suenori Chiku, Kazuhiko Aoyagi, Hiroki Sasaki, Shumpei Ohnami, Kazuyoshi Yanagihara, Kyong Ah Yoon, Myeong Cherl Kook, Yeon Su Lee, Sook Ryun Park, Chan Gyoo Kim, Il Ju Choi, Teruhiko Yoshida, Yusuke Nakamura, Setsuo Hirohashi

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

346 Citations (Scopus)

Abstract

Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 × 10^-9). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r² = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 × 10^-11). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.

Original language	English
Pages (from-to)	730-740
Number of pages	11
Journal	Nature genetics
Volume	40
Issue number	6
DOIs	https://doi.org/10.1038/ng.152
Publication status	Published - 2008 Jun

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.152

Cite this

Sakamoto, H., Yoshimura, K., Saeki, N., Katai, H., Shimoda, T., Matsuno, Y., Saito, D., Sugimura, H., Tanioka, F., Kato, S., Matsukura, N., Matsuda, N., Nakamura, T., Hyodo, I., Nishina, T., Yasui, W., Hirose, H., Hayashi, M., Toshiro, E., ... Hirohashi, S. (2008). Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nature genetics, 40(6), 730-740. https://doi.org/10.1038/ng.152

Sakamoto, H, Yoshimura, K, Saeki, N, Katai, H, Shimoda, T, Matsuno, Y, Saito, D, Sugimura, H, Tanioka, F, Kato, S, Matsukura, N, Matsuda, N, Nakamura, T, Hyodo, I, Nishina, T, Yasui, W, Hirose, H, Hayashi, M, Toshiro, E, Ohnami, S, Sekine, A, Sato, Y, Totsuka, H, Ando, M, Takemura, R, Takahashi, Y, Ohdaira, M, Aoki, K, Honmyo, I, Chiku, S, Aoyagi, K, Sasaki, H, Ohnami, S, Yanagihara, K, Yoon, KA, Kook, MC, Lee, YS, Park, SR, Kim, CG, Choi, IJ, Yoshida, T, Nakamura, Y & Hirohashi, S 2008, 'Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer', Nature genetics, vol. 40, no. 6, pp. 730-740. https://doi.org/10.1038/ng.152

@article{f0bee469d28146cd936918abcd55aeda,

title = "Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer",

abstract = "Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 × 10-9). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r2 = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 × 10-11). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.",

author = "Hiromi Sakamoto and Kimio Yoshimura and Norihisa Saeki and Hitoshi Katai and Tadakazu Shimoda and Yoshihiro Matsuno and Daizo Saito and Haruhiko Sugimura and Fumihiko Tanioka and Shunji Kato and Norio Matsukura and Noriko Matsuda and Tsuneya Nakamura and Ichinosuke Hyodo and Tomohiro Nishina and Wataru Yasui and Hiroshi Hirose and Matsuhiko Hayashi and Emi Toshiro and Sumiko Ohnami and Akihiro Sekine and Yasunori Sato and Hirohiko Totsuka and Masataka Ando and Ryo Takemura and Yoriko Takahashi and Minoru Ohdaira and Kenichi Aoki and Izumi Honmyo and Suenori Chiku and Kazuhiko Aoyagi and Hiroki Sasaki and Shumpei Ohnami and Kazuyoshi Yanagihara and Yoon, {Kyong Ah} and Kook, {Myeong Cherl} and Lee, {Yeon Su} and Park, {Sook Ryun} and Kim, {Chan Gyoo} and Choi, {Il Ju} and Teruhiko Yoshida and Yusuke Nakamura and Setsuo Hirohashi",

note = "Funding Information: This work was supported in Japan by the program for promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio) and by Health and Labour Sciences Research Grants by Ministry of Health, Labour and Welfare. The Korean part of the study was supported by grant 0710340 from the National Cancer Center, Korea. We thank the following people (listed in alphabetical order) for discussion and technical and statistical assistance: M. Asako, T. Chujo, C. Hamada, T. Hayashida, C. Hirama, F. Igarashi, T. Imai, E. Inoue, S. Kamakami, A. Katoh, O. Kawaguchi, C. Kina, N. Kurata, Y. Liu, G. Maeno, S. Mimaki, N. Mitsuhashi, N. Miyahara, A. Miyaoka, R. Nakajima, J. Nakata, Y. Odaka, T. Ogiwara, N. Ohsawa, E. Ohshima, M. Okada, M. Okuyama, Y. Sakashita, M. Sato, M. Seishi, T. Sobue, H. Suganami, E. Takemoto, T. Taniguchi, S. Uchida, T. Urushidate, M. Ushiama, S. Yabe, N. Yamaguchi, S. Yamamoto and I. Yoshimura.",

year = "2008",

month = jun,

doi = "10.1038/ng.152",

language = "English",

volume = "40",

pages = "730--740",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer

AU - Sakamoto, Hiromi

AU - Yoshimura, Kimio

AU - Saeki, Norihisa

AU - Katai, Hitoshi

AU - Shimoda, Tadakazu

AU - Matsuno, Yoshihiro

AU - Saito, Daizo

AU - Sugimura, Haruhiko

AU - Tanioka, Fumihiko

AU - Kato, Shunji

AU - Matsukura, Norio

AU - Matsuda, Noriko

AU - Nakamura, Tsuneya

AU - Hyodo, Ichinosuke

AU - Nishina, Tomohiro

AU - Yasui, Wataru

AU - Hirose, Hiroshi

AU - Hayashi, Matsuhiko

AU - Toshiro, Emi

AU - Ohnami, Sumiko

AU - Sekine, Akihiro

AU - Sato, Yasunori

AU - Totsuka, Hirohiko

AU - Ando, Masataka

AU - Takemura, Ryo

AU - Takahashi, Yoriko

AU - Ohdaira, Minoru

AU - Aoki, Kenichi

AU - Honmyo, Izumi

AU - Chiku, Suenori

AU - Aoyagi, Kazuhiko

AU - Sasaki, Hiroki

AU - Ohnami, Shumpei

AU - Yanagihara, Kazuyoshi

AU - Yoon, Kyong Ah

AU - Kook, Myeong Cherl

AU - Lee, Yeon Su

AU - Park, Sook Ryun

AU - Kim, Chan Gyoo

AU - Choi, Il Ju

AU - Yoshida, Teruhiko

AU - Nakamura, Yusuke

AU - Hirohashi, Setsuo

N1 - Funding Information: This work was supported in Japan by the program for promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio) and by Health and Labour Sciences Research Grants by Ministry of Health, Labour and Welfare. The Korean part of the study was supported by grant 0710340 from the National Cancer Center, Korea. We thank the following people (listed in alphabetical order) for discussion and technical and statistical assistance: M. Asako, T. Chujo, C. Hamada, T. Hayashida, C. Hirama, F. Igarashi, T. Imai, E. Inoue, S. Kamakami, A. Katoh, O. Kawaguchi, C. Kina, N. Kurata, Y. Liu, G. Maeno, S. Mimaki, N. Mitsuhashi, N. Miyahara, A. Miyaoka, R. Nakajima, J. Nakata, Y. Odaka, T. Ogiwara, N. Ohsawa, E. Ohshima, M. Okada, M. Okuyama, Y. Sakashita, M. Sato, M. Seishi, T. Sobue, H. Suganami, E. Takemoto, T. Taniguchi, S. Uchida, T. Urushidate, M. Ushiama, S. Yabe, N. Yamaguchi, S. Yamamoto and I. Yoshimura.

PY - 2008/6

Y1 - 2008/6

N2 - Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 × 10-9). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r2 = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 × 10-11). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.

AB - Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 × 10-9). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r2 = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 × 10-11). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.

UR - http://www.scopus.com/inward/record.url?scp=44349178008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44349178008&partnerID=8YFLogxK

U2 - 10.1038/ng.152

DO - 10.1038/ng.152

M3 - Article

C2 - 18488030

AN - SCOPUS:44349178008

SN - 1061-4036

VL - 40

SP - 730

EP - 740

JO - Nature genetics

JF - Nature genetics

IS - 6

ER -

Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this