Genome wide association study to explore drinking behavior in Japanese

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26253041
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: 松尾 恵太郎 愛知県がんセンター(研究所), 遺伝子医療研究部, 部長 (80393122)
• Co-Investigator(Kenkyū-buntansha): 大中 佳三 九州大学, 医学研究院, 講師 (30325518) ; 山本 健 久留米大学, 医学部, 教授 (60274528) ; 細野 覚代 愛知県がんセンター(研究所), 疫学・予防部, 主任研究員 (80402600)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ALDH2 / alcohol drinking / GWAS / polymorphism

Outline of Annual Research Achievements

初年度、第2年度に実施した愛知県がんセンターにおける全ゲノム関連解析(Phase I)において、飲酒行動と全ゲノムレベルで有意に関連を示す遺伝子多型は既知のALDH2 rs671のみであった。またこの遺伝子多型を考慮した上で、さらに全ゲノムレベル有意に関連を示す遺伝子座も認められなかった。以下の二つのアプローチに基づき、検討を実施した。
①rs671は既存研究でも報告されており、当初計画で想定していたPhase IIの検証研究をスキップし、rs671との関連検討並びに飲酒との各種疾患リスクに対する交互作用の検討を行った。②Phase I研究を行う飲酒に関する対象集団を日本多施設共同コホート研究(J-MICC)の横断研究GWASデータを追加し、新規遺伝子座を明らかにする。
①に関して、昨年度報告した膀胱がんリスク(Masaoka et al. Carcinogenesis 2016)、頭頸部・食道がん(Koyanagi et al. Eur J Cancer Prev 2016)に加え、乳がん・卵巣がんに関して、乳がん疫学研究国際コンソーシアム(BCAC)、卵巣がん疫学研究国際コンソーシアム(OCAC)との共同研究として、ALDH2多型、飲酒習慣との関連に関して検討を行い、遺伝子環境要因交互作用が存在しないことを確認した。またALDH2が喫煙行動と関連することを新たに見いだした(Masaoka et al. Nicotine Tob Res 2016, Drug Alcohol Depend 2017)。②に関しては粗解析の段階で明らかな遺伝子座が認められないことを確認し、本アプローチによる更なる研究トピックの追究が難しい事を確認している。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] National Cancer Insitute(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: National Cancer Insitute
• [Int'l Joint Research] Mario Negri Institute(Italy)
  • Country Name: Italy
  • Counterpart Institution: Mario Negri Institute
• [Int'l Joint Research] Cambridge University(英国)
  • Country Name: UNITED KINGDOM
  • Counterpart Institution: Cambridge University
• [Journal Article] Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study. (2017)
  • Author(s): Sawabe M, Ito H, Oze I, Hosono S, Kawakita D, Tanaka H, Hasegawa Y, Murakami S, Matsuo K.
  • Journal Title: Cancer Sci Volume: 108 Pages: 91-100
  • DOI: 10.1111/cas.13115.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Aldehyde Dehydrogenase 2 Polymorphism Is a Predictor of Smoking Cessation. (2017)
  • Author(s): Masaoka H, Gallus S, Ito H, Watanabe M, Yokomizo A, Eto M, Matsuo K.
  • Journal Title: Nicotine Tob Res Volume: 未定 Pages: 未定
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Combination of ALDH2 and ADH1B polymorphisms is associated with smoking initiation: A large-scale cross-sectional study in a Japanese population. (2017)
  • Author(s): Masaoka H, Ito H, Gallus S, Watanabe M, Yokomizo A, Eto M, Matsuo K.
  • Journal Title: Drug Alcohol Depend Volume: 173 Pages: 85-91
  • DOI: 10.1016/j.drugalcdep.2016.12.015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study. (2017)
  • Author(s): Fehringer G, Brenner DR, Zhang ZF, Lee YA, Matsuo K, et al.
  • Journal Title: Int J Cancer Volume: 140 Pages: 1976-1984
  • DOI: 10.1002/ijc.30618.
  • Peer Reviewed
• [Journal Article] Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations. (2017)
  • Author(s): Seow WJ, Matsuo K, Hsiung CA, et al.
  • Journal Title: Hum Mol Genet Volume: 26 Pages: 454-465
  • DOI: 10.1093/hmg/ddw414.
  • Peer Reviewed
• [Journal Article] Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) polymorphisms exacerbate bladder cancer risk associated with alcohol drinking: gene-environment interaction. (2016)
  • Author(s): Masaoka H, Ito H, Soga N, Hosono S, Oze I, Watanabe M, Tanaka H, Yokomizo A, Hayashi N, Eto M, Matsuo K.
  • Journal Title: Carcinogenesis Volume: 37 Pages: 583-585
  • DOI: 10.1093/carcin/bgw033
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The phenotype and clinical course of Japanese Fanconi Anaemia infants is influenced by patient, but not maternal ALDH2 genotype. (2016)
  • Author(s): Yabe M, Yabe H, Morimoto T, Fukumura A, Ohtsubo K, Koike T, Yoshida K, Ogawa S, Ito E, Okuno Y, Muramatsu H, Kojima S, Matsuo K, Hira A, Takata M.
  • Journal Title: Brit J Haematol Volume: 175 Pages: 457-461
  • DOI: 10.1111/bjh.14243
  • Peer Reviewed
• [Presentation] Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer based on aldehyde dehydrogenase 2 (ALDH2) genotype and alcohol consumption in a Japanese population (2016)
  • Author(s): Koyanagi Y, Ito H, Oze I, Hosono S, Tanaka H, Abe T, Shimizu Y, Hasegawa Y, Matsuo K.
  • Organizer: European Association of Cancer Research Biennial Meeting
  • Place of Presentation: Manchester
  • Year and Date: 2016-07-09 – 2016-07-12
  • Int'l Joint Research
• [Presentation] ALDH2 and ADH1B polymorphisms exacerbate bladder cancer risk associated with alcohol drinking. (2016)
  • Author(s): Masaoka H, Ito H, Soga N, Yokomizo A, Eto M, Matsuo K.
  • Organizer: European Association of Cancer Research Biennial Meeting
  • Place of Presentation: Manchester
  • Year and Date: 2016-07-09 – 2016-07-12
  • Int'l Joint Research
• [Presentation] ALDH2 Glu504Lys polymorphism and breast cancer risk: Analysis of 6,624 cases and 5,750 controls from the Breast Cancer Association Consortium (2016)
  • Author(s): Ugai T, Milne RL, Ito H, Matsuo K.
  • Organizer: American Association of Cancer Research Annual Meeting 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-04-16 – 2016-04-20
  • Int'l Joint Research