Investigation of genetic factors associated with the risk of Helicobacter pylori-induced gastric cancer and gastric atrophy by SNP-set analysis and their validation

• Project/Area Number: 16K09032
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Epidemiology and preventive medicine
• Research Institution: Nagoya University
• Principal Investigator: Hishida Asahi 名古屋大学, 医学系研究科, 准教授 (40447339)
• Co-Investigator(Kenkyū-buntansha): 渡辺 能行 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00191809) ; 細野 晃弘 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00723454) ; 内藤 真理子 広島大学, 医系科学研究科(歯), 教授 (10378010) ; 渡邉 美貴 愛知県がんセンター(研究所), その他部局等, その他 (60773695)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ゲノム疫学 / 胃がん / ヘリコバクター・ピロリ / 前がん病変 / 予防医学 / 萎縮性胃炎 / ヘリコバクターピロリ / 遺伝子多型 / 分子疫学 / がん予防 / ピロリ菌関連胃癌 / ゲノムワイド関連研究（GWAS） / ピロリ菌 / 遺伝疫学 / 胃がん予防 / ゲノム / 感染症 / がん / 遺伝学

Outline of Final Research Achievements

We conducted the genome-wide association study (GWAS) of gastric atrophy (GA) (diagnosed based on pepsinogen 1 [PG1] <= 70ng/ml & PG1/PG2 <= 3), severe gastric atrophy (sGA) (PG1 <= 30ng/ml & PG1/PG2 <= 2) and PG1/PG2 ratio using the data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study (n = 3,385) and Hospital-based Epidemiologic Research Program at Aichi Cancer Center 2 (HERPACC2)(n = 2,885), and found that PSCA SNPs on 8q24.3, which also reportedly associate with the risk of Helicobacter pylori-induced gastric cancer, reached the GWAS significant levels, and subsequent SNP-set analysis supported these findings by the statistically significant associations of PSCA gene with each of the three traits of GA, sGA and PG1/PG2 ratio.

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、日本人に多いピロリ菌関連胃がんの前がん病変である、ピロリ菌関連萎縮性胃炎の遺伝的要因が、全ゲノムレベルでPSCA遺伝子にあることが明らかになり、将来の遺伝的体質に基づくピロリ菌関連胃がん及び萎縮性胃炎の個別化予防のための有用な情報（具体的には、事前に疾患リスクを知ることによる、ピロリ菌除菌や、胃がん検診受診などの行動へのきっかけ作り、等）を提供できたものと考えている。

Research Products

• [Journal Article] GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy. (2019)
  • Author(s): Hishida A, Ugai T, Fujii R, Nakatochi M, Wu MC, Ito H, Oze I, Tajika M, Niwa Y, Nishiyama T, Nakagawa-Senda H, Suzuki S, Koyama T, Matsui D, Watanabe Y, Kawaguchi T, Matsuda F, Momozawa Y, Kubo M, Naito M, Matsuo K, Wakai K.
  • Journal Title: Carcinogenesis Volume: - Issue: 5 Pages: 661-668
  • DOI: 10.1093/carcin/bgz016
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The association of PSCA gene and H.pylori-related gastric atrophy risk detected by GWAS and SKAT. (2018)
  • Author(s): Hishida A, Fujii R, Nakatochi M, Kawai S, Ito H, Matsuo K, Watanabe M, Suzuki S, Kuriyama N, Naito M, Wakai K.
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] The association between the TLR2 gene and risk of H. pylori-related gastric atrophy detected by SNP-set Kernel Association Tests (SKAT) (2017)
  • Author(s): Asahi Hishida, Ryosuke Fujii, Masahiro Nakatochi, Sayo Kawai, Isao Oze, Keitaro Matsuo, Yuya Tamai, Sadao Suzuki, Nagato Kuriyama, Yoshiyuki Watanabe, Mariko Naito, Kenji Wakai
  • Organizer: 第76回日本癌学会学術総会（横浜）