Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21

Chizu Tanikawa; Yoichiro Kamatani; Osamu Toyoshima; Hiromi Sakamoto; Hidemi Ito; Atsushi Takahashi; Yukihide Momozawa; Makoto Hirata; Nobuo Fuse; Takako Takai-Igarashi; Atsushi Shimizu; Makoto Sasaki; Taiki Yamaji; Norie Sawada; Motoki Iwasaki; Shoichiro Tsugane; Mariko Naito; Asahi Hishida; Kenji Wakai; Norihiro Furusyo; Yoshinori Murakami; Yusuke Nakamura; Issei Imoto; Johji Inazawa; Isao Oze; Naomi Sato; Fumihiko Tanioka; Haruhiko Sugimura; Hiroshi Hirose; Teruhiko Yoshida; Keitaro Matsuo; Michiaki Kubo; Koichi Matsuda

doi:10.1111/cas.13815

Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21

Chizu Tanikawa, Yoichiro Kamatani, Osamu Toyoshima, Hiromi Sakamoto, Hidemi Ito, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Nobuo Fuse, Takako Takai-Igarashi, Atsushi Shimizu, Makoto Sasaki, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Mariko Naito, Asahi Hishida, Kenji Wakai, Norihiro FurusyoYoshinori Murakami, Yusuke Nakamura, Issei Imoto, Johji Inazawa, Isao Oze, Naomi Sato, Fumihiko Tanioka, Haruhiko Sugimura, Hiroshi Hirose, Teruhiko Yoshida, Keitaro Matsuo, Michiaki Kubo, Koichi Matsuda

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Abstract

Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10⁻⁸ with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10⁻¹⁰ with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10⁻¹³ with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10⁻¹¹), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.

Original language	English
Pages (from-to)	4015-4024
Number of pages	10
Journal	Cancer science
Volume	109
Issue number	12
DOIs	https://doi.org/10.1111/cas.13815
Publication status	Published - 2018 Dec

Keywords

ABO
CUX2
DEFB
gastric cancer
genome-wide association study

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

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10.1111/cas.13815

Cite this

Tanikawa, C., Kamatani, Y., Toyoshima, O., Sakamoto, H., Ito, H., Takahashi, A., Momozawa, Y., Hirata, M., Fuse, N., Takai-Igarashi, T., Shimizu, A., Sasaki, M., Yamaji, T., Sawada, N., Iwasaki, M., Tsugane, S., Naito, M., Hishida, A., Wakai, K., ... Matsuda, K. (2018). Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. Cancer science, 109(12), 4015-4024. https://doi.org/10.1111/cas.13815

Tanikawa, C, Kamatani, Y, Toyoshima, O, Sakamoto, H, Ito, H, Takahashi, A, Momozawa, Y, Hirata, M, Fuse, N, Takai-Igarashi, T, Shimizu, A, Sasaki, M, Yamaji, T, Sawada, N, Iwasaki, M, Tsugane, S, Naito, M, Hishida, A, Wakai, K, Furusyo, N, Murakami, Y, Nakamura, Y, Imoto, I, Inazawa, J, Oze, I, Sato, N, Tanioka, F, Sugimura, H, Hirose, H, Yoshida, T, Matsuo, K, Kubo, M & Matsuda, K 2018, 'Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21', Cancer science, vol. 109, no. 12, pp. 4015-4024. https://doi.org/10.1111/cas.13815

@article{ca526fa8277e4d1f8753206673bc33ad,

title = "Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21",

abstract = "Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.",

keywords = "ABO, CUX2, DEFB, gastric cancer, genome-wide association study",

author = "Chizu Tanikawa and Yoichiro Kamatani and Osamu Toyoshima and Hiromi Sakamoto and Hidemi Ito and Atsushi Takahashi and Yukihide Momozawa and Makoto Hirata and Nobuo Fuse and Takako Takai-Igarashi and Atsushi Shimizu and Makoto Sasaki and Taiki Yamaji and Norie Sawada and Motoki Iwasaki and Shoichiro Tsugane and Mariko Naito and Asahi Hishida and Kenji Wakai and Norihiro Furusyo and Yoshinori Murakami and Yusuke Nakamura and Issei Imoto and Johji Inazawa and Isao Oze and Naomi Sato and Fumihiko Tanioka and Haruhiko Sugimura and Hiroshi Hirose and Teruhiko Yoshida and Keitaro Matsuo and Michiaki Kubo and Koichi Matsuda",

note = "Funding Information: We thank all the participants in this study. We would like to express our gratefulness to the staff of BioBank Japan, Tohoku Medical Megabank, Iwate Tohoku Medical Megabank, J-MICC, and JPHC for their outstanding assistance. This study was partially supported by the BioBank Japan project and the Tohoku Medical Megabank project, which is supported by the Ministry of Education, Culture, Sports, Sciences and Technology Japan and the Japan Agency for Medical Research and Development. The JPHC Study was supported by the National Cancer Research and Development Fund since 2010 and was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan from 1989 to 2010. The J-MICC Study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (17015018) and Innovative Areas (221S0001) and the JSPS KAKENHI Grant (16H06277) from the Japan Ministry of Education, Science, Sports, Culture and Technology. This study was also supported by JSPS KAKENHI Grants (25293168 to Ko.M and 15K08792 to Ke. M.). Funding Information: Japan Agency for Medical Research and Development; Ministry of Health, Labour and Welfare; Grant-in-Aid for Cancer Research; National Cancer Research and Development Fund; Japan Society for the Promotion of Science, Grant/Award Number: 15K08792 and 25293168; Ministry of Education, Culture, Sports, Science and Technology, Grant/Award Number: 16H06277, 17015018 and 221S0001 Publisher Copyright: {\textcopyright} 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2018",

month = dec,

doi = "10.1111/cas.13815",

language = "English",

volume = "109",

pages = "4015--4024",

journal = "Cancer science",

issn = "1347-9032",

publisher = "Wiley-Blackwell",

number = "12",

}

TY - JOUR

T1 - Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21

AU - Tanikawa, Chizu

AU - Kamatani, Yoichiro

AU - Toyoshima, Osamu

AU - Sakamoto, Hiromi

AU - Ito, Hidemi

AU - Takahashi, Atsushi

AU - Momozawa, Yukihide

AU - Hirata, Makoto

AU - Fuse, Nobuo

AU - Takai-Igarashi, Takako

AU - Shimizu, Atsushi

AU - Sasaki, Makoto

AU - Yamaji, Taiki

AU - Sawada, Norie

AU - Iwasaki, Motoki

AU - Tsugane, Shoichiro

AU - Naito, Mariko

AU - Hishida, Asahi

AU - Wakai, Kenji

AU - Furusyo, Norihiro

AU - Murakami, Yoshinori

AU - Nakamura, Yusuke

AU - Imoto, Issei

AU - Inazawa, Johji

AU - Oze, Isao

AU - Sato, Naomi

AU - Tanioka, Fumihiko

AU - Sugimura, Haruhiko

AU - Hirose, Hiroshi

AU - Yoshida, Teruhiko

AU - Matsuo, Keitaro

AU - Kubo, Michiaki

AU - Matsuda, Koichi

N1 - Funding Information: We thank all the participants in this study. We would like to express our gratefulness to the staff of BioBank Japan, Tohoku Medical Megabank, Iwate Tohoku Medical Megabank, J-MICC, and JPHC for their outstanding assistance. This study was partially supported by the BioBank Japan project and the Tohoku Medical Megabank project, which is supported by the Ministry of Education, Culture, Sports, Sciences and Technology Japan and the Japan Agency for Medical Research and Development. The JPHC Study was supported by the National Cancer Research and Development Fund since 2010 and was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan from 1989 to 2010. The J-MICC Study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (17015018) and Innovative Areas (221S0001) and the JSPS KAKENHI Grant (16H06277) from the Japan Ministry of Education, Science, Sports, Culture and Technology. This study was also supported by JSPS KAKENHI Grants (25293168 to Ko.M and 15K08792 to Ke. M.). Funding Information: Japan Agency for Medical Research and Development; Ministry of Health, Labour and Welfare; Grant-in-Aid for Cancer Research; National Cancer Research and Development Fund; Japan Society for the Promotion of Science, Grant/Award Number: 15K08792 and 25293168; Ministry of Education, Culture, Sports, Science and Technology, Grant/Award Number: 16H06277, 17015018 and 221S0001 Publisher Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

PY - 2018/12

Y1 - 2018/12

N2 - Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.

AB - Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.

KW - ABO

KW - CUX2

KW - DEFB

KW - gastric cancer

KW - genome-wide association study

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U2 - 10.1111/cas.13815

DO - 10.1111/cas.13815

M3 - Article

C2 - 30281874

AN - SCOPUS:85055877351

SN - 1347-9032

VL - 109

SP - 4015

EP - 4024

JO - Cancer science

JF - Cancer science

IS - 12

ER -

Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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