Risk prediction for gastric cancer using GWAS-identified polymorphisms, Helicobacter pylori infection and lifestyle-related risk factors in a Japanese population

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15K08792
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: 伊藤 秀美 愛知県がんセンター(研究所), 遺伝子医療研究部, 室長 (90393123)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 胃がん / リスク予測 / 遺伝的要因 / 遺伝子多型 / ピロリ菌感染 / 喫煙 / 野菜果物摂取 / 個別化予防

Outline of Annual Research Achievements

平成28年度から29年度にかけて、2つの独立した症例対照研究（HERPACC2, HERPACC3）を実施し、喫煙、野菜果物摂取、ピロリ菌感染と胃粘膜萎縮とを組み合わせたABC分類を使ったリスク予測よりも、PSCA遺伝子多型（rs2294008,）を加えることでリスク予測精度が統計学的有意に上昇することを示した。
平成30年度は、既報のGWAS研究により同定された10個の胃がん感受性遺伝子多型のうち、HERPACC2（症例697例と性と年齢を適合させた対照者1372例）ならびにHERPACC3（症例678例と性と年齢を適合させた対照者678例）の症例対照研究において胃がんリスクと関連を示した多型を３つ（PRLAA1-rs10074991、 UNC5CL-rs2294693、ASH1L-rs80142782）を加えて、リスク予測精度を評価した。
喫煙、野菜果物摂取、ABC分類による分類と4つの遺伝子多型を含むリスク予測モデルのROS解析によるAUCは、それぞれの症例対照研究において、0.79 (95%信頼区間, 0.77-0.81)と0.80 (0.77-0.82)と、精度が高かった。しかし、PSCA遺伝子多型のみを加えたリスク予測モデルと比べ、精度はほとんど変わらなかった（喫煙、野菜果物摂取、ABC分類とPACA遺伝子多型によるリスク予測モデルのAUCは、それぞれの研究で0.78 (0.76-0.80) と0.80 (0.77-0.82)であった）。
本研究で開発した喫煙、野菜果物摂取、ABC分類とPACA遺伝子多型によるリスク予測モデルは、日本人における胃がんのハイリスク群を補足でき、胃がんの個別化予防プログラムへの応用の可能性を示唆するものであった。

Research Products

• [Int'l Joint Research] University of Milan/Mario Negri Institute/University of Cattolica(Italy)
  • Country Name: Italy
  • Counterpart Institution: University of Milan/Mario Negri Institute/University of Cattolica
• [Int'l Joint Research] UCLA Fielding School of Public Health/Icahn School of Medicine at Mount Sinai/University of Buffalo(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: UCLA Fielding School of Public Health/Icahn School of Medicine at Mount Sinai/University of Buffalo
  • # of Other Institutions: 3
• [Int'l Joint Research] University of Porto Medical School(ポルトガル)
  • Country Name: PORTUGAL
  • Counterpart Institution: University of Porto Medical School
• [Int'l Joint Research] University of Ottawa/Public Health Agency of Canada(Canada)
  • Country Name: Canada
  • Counterpart Institution: University of Ottawa/Public Health Agency of Canada
• [Int'l Joint Research] Lausanne University Hospital(Switzerland)
  • Country Name: Switzerland
  • Counterpart Institution: Lausanne University Hospital
• [Int'l Joint Research]
  • # of Other Countries: 2
• [Journal Article] Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis. (2018)
  • Author(s): Ishioka K, Masaoka H, Ito H, Oze I, Ito S, Tajika M, Shimizu Y, Niwa Y, Nakamura S, Matsuo K.
  • Journal Title: Gastric Cancer Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1007/s10120-018-0823-0
  • Peer Reviewed
• [Journal Article] Cigarette smoking and gastric cancer in the Stomach Cancer Pooling (StoP) Project. (2018)
  • Author(s): Praud D, Rota M, Pelucchi C, Bertuccio P, Rosso T, Galeone C, Zhang ZF, Matsuo K, Ito H, Boffetta P, Boccia S, Negri E, La Vecchia C, et al.
  • Journal Title: Eur J Cancer Prev Volume: 27(2) Pages: 124-133
  • DOI: 10.1097/CEJ.0000000000000290
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis. (2017)
  • Author(s): Toyoshima O, Tanikawa C, Yamamoto R, Watanabe H, Yamashita H, Sakitani K, Yoshida S, Kubo M, Matsuo K, Ito H, Koike K, Seto Y, Matsuda K
  • Journal Title: Oncotarget Volume: 9(3) Pages: 3936-3945
  • DOI: 10.18632/oncotarget.23278
  • Peer Reviewed / Open Access
• [Journal Article] The more from East-Asian, the better: risk prediction of colorectal cancer risk by GWAS-identified SNPs among Japanese. (2017)
  • Author(s): Abe M, Ito H, Oze I, Nomura M, Ogawa Y, Matsuo K.
  • Journal Title: J Cancer Res Clin Oncol. Volume: 143(12) Pages: 2481-2492
  • DOI: 10.1007/s00432-017-2505-4
  • Peer Reviewed
• [Journal Article] Alcohol consumption and gastric cancer risk-A pooled analysis within the StoP project consortium. (2017)
  • Author(s): Rota M, Pelucchi C, Bertuccio P, Matsuo K, Zhang ZF, Ito H, Boffetta P, Boccia S, Negri E, La Vecchia C, et al.
  • Journal Title: Int J Cancer Volume: 141(10) Pages: 1950-1962
  • DOI: 10.1002/ijc.30891
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Prediction of breast cancer risk based on common genetic variants in Japanes e women. (2017)
  • Author(s): Ito H, Iwasaki M, Koriyama C, Taniyama Y, Oze I, Imoto I, Ohno Y, Tsugane S, Iwata H, Matsuo K
  • Organizer: 第76回日本癌学会学術総会