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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Pages (from-to)4015-4024
Number of pages10
JournalCancer science
Volume109
Issue number12
DOIs
Publication statusPublished - 12-2018

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Genome-Wide Association Study
Stomach Neoplasms
Odds Ratio
Helicobacter Infections
Multigene Family
Helicobacter pylori
Introns
Stomach
Japan
Mucous Membrane
Gene Expression
Peptides
Mortality
Population
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tanikawa, C., Kamatani, Y., Toyoshima, O., Sakamoto, H., Ito, H., Takahashi, A., ... 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, Chizu ; Kamatani, Yoichiro ; Toyoshima, Osamu ; Sakamoto, Hiromi ; Ito, Hidemi ; Takahashi, Atsushi ; Momozawa, Yukihide ; Hirata, Makoto ; Fuse, Nobuo ; Takai-Igarashi, Takako ; Shimizu, Atsushi ; Sasaki, Makoto ; Yamaji, Taiki ; Sawada, Norie ; Iwasaki, Motoki ; Tsugane, Shoichiro ; Naito, Mariko ; Hishida, Asahi ; Wakai, Kenji ; Furusyo, Norihiro ; Murakami, Yoshinori ; Nakamura, Yusuke ; Imoto, Issei ; Inazawa, Johji ; Oze, Isao ; Sato, Naomi ; Tanioka, Fumihiko ; Sugimura, Haruhiko ; Hirose, Hiroshi ; Yoshida, Teruhiko ; Matsuo, Keitaro ; Kubo, Michiaki ; Matsuda, Koichi. / Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. In: Cancer science. 2018 ; Vol. 109, No. 12. pp. 4015-4024.
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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.",
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",
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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

Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. / Tanikawa, Chizu; Kamatani, Yoichiro; Toyoshima, Osamu; Sakamoto, Hiromi; Ito, Hidemi; Takahashi, Atsushi; Momozawa, Yukihide; Hirata, Makoto; Fuse, Nobuo; Takai-Igarashi, Takako; Shimizu, Atsushi; Sasaki, Makoto; Yamaji, Taiki; Sawada, Norie; Iwasaki, Motoki; Tsugane, Shoichiro; Naito, Mariko; Hishida, Asahi; Wakai, Kenji; Furusyo, Norihiro; Murakami, Yoshinori; Nakamura, Yusuke; Imoto, Issei; Inazawa, Johji; Oze, Isao; Sato, Naomi; Tanioka, Fumihiko; Sugimura, Haruhiko; Hirose, Hiroshi; Yoshida, Teruhiko; Matsuo, Keitaro; Kubo, Michiaki; Matsuda, Koichi.

In: Cancer science, Vol. 109, No. 12, 12.2018, p. 4015-4024.

Research output: Contribution to journalArticle

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

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.

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Tanikawa C, Kamatani Y, Toyoshima O, Sakamoto H, Ito H, Takahashi A et al. Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. Cancer science. 2018 Dec;109(12):4015-4024. https://doi.org/10.1111/cas.13815