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• Project/Area Number: 24590776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene
• Research Institution: 愛知県がんセンター(研究所)
• Principal Investigator: ITO Hidemi 愛知県がんセンター(研究所), 疫学・予防部, 室長 (90393123)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 分子遺伝疫学 / 乳がん / リスク予測 / 遺伝的リスク要因 / 個別化予防

Research Abstract

We analyzed 56 single nucleotide polymorphisms (SNPs) identified in previous GWASs and conducted a case-control study with 697 case subjects and 1,394 age- and menopausal status-matched controls within the framework of Hospital-based Epidemiological Research Program at Acihi Cancer Center. Among 56 SNPs, 23 was selected to built a risk prediction model for breast cancer. We evaluated the prediction models using AUC (Area Under the Curve) in receiver-operating characteristic (ROC). The AUC for a model including the genetic risk score in addition to the conventional risk factors was 0.726, versus 0.675 with the conventional risk factors only (P <0.05). In conclusion, we identified a genetic risk predictor of breast cancer in a Japanese population. Identification of additional new loci in the GWASs among Asian or Japanese populations is needed to establish more accurate risk prediction model.

Research Products

• [Journal Article] FGF receptor genes and breast cancer susceptibility : results from the Breast Cancer Association Consortium (2014)
  • Author(s): Agarwal D, Pineda S, Michailidou K et al
  • Journal Title: Br J Cancer Volume: 110 Pages: 1088-1100
  • Peer Reviewed
• [Journal Article] FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium. (2014)
  • Author(s): Agarwal D, Pineda S, Michailidou K, … Matsuo K, Ito H, … Zamora P, Benitez J and Milne RL.
  • Journal Title: Br J Cancer Volume: 110 Issue: 4 Pages: 1088-100
  • DOI: 10.1038/bjc.2013.769
  • Peer Reviewed
• [Journal Article] Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers (2013)
  • Author(s): French JD, Ghoussaini M, Edwards SL et al
  • Journal Title: Am J Hum Genet Volume: 92 Pages: 489-503
  • Peer Reviewed
• [Journal Article] Genome-wide association studies identify four ER negative-specific breast cancer risk loci (2013)
  • Author(s): Garcia-Closas M, Couch FJ, Lindstrom S et al
  • Journal Title: Nat Genet Volume: 45
  • Peer Reviewed
• [Journal Article] Alcohol and dietary folate intake and the risk of breast cancer : a case-control study in Japan (2013)
  • Author(s): Islam T, Ito H, Sueta A et al
  • Journal Title: Eur J Cancer Prev Volume: 22 Pages: 358-366
• [Journal Article] Fine-scale mapping of the FGFR2 breast cancer risk locus : putative functional variants differentially bind FOXA1 and E2F1 (2013)
  • Author(s): Meyer KB, O'Reilly M, Michailidou K et al
  • Journal Title: Am J Hum Genet Volume: 93 Pages: 1046-1060
  • Peer Reviewed
• [Journal Article] Large-scale genotyping identifies 41 new loci associated with breast cancer risk (2013)
  • Author(s): Michailidou K, Hall P, Gonzalez-Neira A et al
  • Journal Title: Nat Genet Volume: 45
  • Peer Reviewed
• [Journal Article] Common genetic determinants of breast-cancer risk in East Asian women : a collaborative study of 23 637 breast cancer cases and 25 579 controls (2013)
  • Author(s): Zheng W, Zhang B, Cai Q et al
  • Journal Title: Hum Mol Genet Volume: 22 Pages: 2539-2550
  • Peer Reviewed
• [Journal Article] Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. (2013)
  • Author(s): French JD, Ghoussaini M, Edwards SL, … Matsuo K, Ito H, … Chenevix-Trench G, Easton DF and Dunning AM.
  • Journal Title: Am J Hum Genet Volume: 92 Issue: 4 Pages: 353-61
  • DOI: 10.1016/j.ajhg.2013.01.002
  • Peer Reviewed
• [Journal Article] Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1. (2013)
  • Author(s): Meyer KB, O'Reilly M, Michailidou K, … Matsuo K, Ito H, … Ponder BA, Dunning AM and Easton DF.
  • Journal Title: Am J Hum Genet Volume: 92 Issue: 6 Pages: 489-503
  • DOI: 10.1016/j.ajhg.2013.10.026
  • Peer Reviewed
• [Journal Article] Alcohol and dietary folate intake and the risk of breast cancer: a case-control study in Japan. (2013)
  • Author(s): Islam T, Ito H, Sueta A, Hosono S, Hirose K, Watanabe M, Iwata H, Tajima K, Tanaka H and Matsuo K.
  • Journal Title: Eur J Cancer Prev Volume: 22 Issue: 4 Pages: 358-66
  • DOI: 10.1097/cej.0b013e32835b6a60
  • Peer Reviewed
• [Journal Article] Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls. (2013)
  • Author(s): Zheng W, Zhang B, Cai Q, … Matsuo K, Ito H, … Iwasaki M, … Shu XO, Easton DF and Kang D.
  • Journal Title: Hum Mol Genet Volume: 22 Issue: 12 Pages: 2539-50
  • DOI: 10.1093/hmg/ddt089
  • Peer Reviewed
• [Journal Article] Large-scale genotyping identifies 41 new loci associated with breast cancer risk (2013)
  • Author(s): Michailidou, K. Hall, P. Gonzalez-Neira, A. Matsuo, K. Ito, H. Iwata, H. Sueta, A. Dunning, A. M. Benitez, J. Easton, D. F. et. al. (他209名）
  • Journal Title: Nat Genet Volume: 45 (4) Issue: 4 Pages: 353-61
  • DOI: 10.1038/ng.2563
  • Peer Reviewed
• [Journal Article] Genome-wide association studies identify four ER negative-specific breast cancer risk loci (2013)
  • Author(s): Garcia-Closas, M. Couch, F. J. Lindstrom, S. Matsuo, K. Ito, H. Iwata, H. Yatabe, Y. Easton, D. F. Haiman, C. A. Kraft, P. (他260名）
  • Journal Title: Nat Genet Volume: 45 (4) Issue: 4 Pages: 392-8
  • DOI: 10.1038/ng.2561
  • Peer Reviewed
• [Journal Article] Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer (2013)
  • Author(s): Bojesen, S. E. Pooley, K. A. Johnatty, S. E. Matsuo, K. Hosono, S. Nakanishi, T. Hartman, M.Ito, H. Iwata, H. Tajima, K. Antoniou, A. C. Chenevix-Trench, G. Dunning, A. M. (他423名）
  • Journal Title: Nat Genet Volume: 45 (4) Issue: 4 Pages: 371-84
  • DOI: 10.1038/ng.2566
  • Peer Reviewed
• [Journal Article] Differential impact of body mass index and its change on the risk of breast cancer by molecular subtype: A case-control study in Japanese women (2013)
  • Author(s): Sueta, A. Ito, H. Islam, T. Hosono, S. Watanabe, M. Hirose, K. Fujita, T. Yatabe, Y. Iwata, H. Tajima, K. Tanaka, H. Iwase, H. Matsuo, K.
  • Journal Title: Springerplus Volume: 1(1) Issue: 1 Pages: 39-39
  • DOI: 10.1186/2193-1801-1-39
  • Peer Reviewed
• [Journal Article] Reproductive and hormonal risk factors for luminal, HER2-overexpressing, and triple-negative breast cancer in Japanese women (2012)
  • Author(s): Islam T, Matsuo K, Ito H et al
  • Journal Title: Ann Oncol Volume: 23 Pages: 2435-2441
• [Journal Article] Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer (2012)
  • Author(s): Long J, Cai Q, Sung H et al
  • Journal Title: PLoS Genet Volume: 8
  • Peer Reviewed
• [Journal Article] Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene : results from a consortium study among Asians (2012)
  • Author(s): Ma X, Beeghly-Fadiel A, Lu W et al
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 21 Pages: 1176-1184
  • Peer Reviewed
• [Journal Article] Breastfeeding and breast cancer risk : an evaluation based on a systematic review of epidemiologic evidence among the Japanese population (2012)
  • Author(s): Nagata C, Mizoue T, Tanaka K et al
  • Journal Title: Jpn J Clin Oncol Volume: 42 Pages: 124-130
  • Peer Reviewed
• [Journal Article] Differential impact of body mass index and its change on the risk of breast cancer by molecular subtype : A case-control study in Japanese women (2012)
  • Author(s): Sueta A, Ito H, Islam T et al
  • Journal Title: Springerplus Volume: 1 Pages: 39-39
• [Journal Article] A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population (2012)
  • Author(s): Sueta A, Ito H, Kawase T et al
  • Journal Title: Breast Cancer Res Treat Volume: 132 Pages: 711-721
  • Peer Reviewed
• [Journal Article] A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population (2012)
  • Author(s): Sueta, A. Ito, H. Kawase, T. Hirose, K. Hosono, S. Yatabe, Y. Tajima, K. Tanaka, H. Iwata, H. Iwase, H. Matsuo, K.
  • Journal Title: Breast Cancer Res Treat Volume: 132 (2) Issue: 2 Pages: 711-21
  • DOI: 10.1007/s10549-011-1904-5
  • Peer Reviewed
• [Journal Article] Reproductive and hormonal risk factors for luminal, HER2-overexpressing, and triple-negative breast cancer in Japanese women (2012)
  • Author(s): Islam, T. Matsuo, K. Ito, H. Hosono, S. Watanabe, M. Iwata, H. Tajima, K. Tanaka, H.
  • Journal Title: Ann Oncol Volume: 23 (9) Issue: 9 Pages: 2435-41
  • DOI: 10.1093/annonc/mdr613
  • Peer Reviewed
• [Presentation] 乳がんの累積リスク-個別化がん予防戦略- (2014)
  • Author(s): 伊藤秀美、細野覚代、尾瀬功、渡邉美貴、田中英夫、松尾恵太郎
  • Organizer: 第24回日本疫学会総会
  • Place of Presentation: 仙台
• [Presentation] 乳がんの累積リスク － 個別化がん予防戦略 － (2014)
  • Author(s): 伊藤秀美、細野覚代、尾瀬功、渡邉美貴、田中英夫、松尾恵太郎
  • Organizer: 第24回日本疫学会学術総会
  • Place of Presentation: 仙台市青年文化センター（仙台市）
• [Presentation] A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population (2012)
  • Author(s): Hidemi Ito, Aiko Sueta, Hiroji Iwata, Satoyo Hosono, Isao Oze, Miki Watanabe, Hirotaka Iwase, Hideo Tanaka, and Keitaro Matsuo
  • Organizer: AACR/MEG Special Conference"Post-GWAS Horizons in Molecular Epidemiology : Digging Deeper into the Environment"
  • Place of Presentation: 米国フロリダ州ハリウッド
• [Presentation] HERPACC研究のゲノムコホートしての可能性 (2012)
  • Author(s): 伊藤秀美
  • Organizer: 第71回日本がん学会学術総会
  • Place of Presentation: 札幌
• [Presentation] A genetic risk predictor for breast cancer using low-penetrance polymorphisms in a Japanese population
  • Author(s): Ito H, Sueta A, Iwata H, Hosono S, Oze I, Watanabe M, Iwase H, Tanaka H, Matsuo K
  • Organizer: The AACR Speceial Conference: Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment
  • Place of Presentation: The Westin Diplomat Resort and Spa（米国フロリダ）
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120430nagasaki.gif
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120518kumamoto.gif
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120606okinawa.gif
• [Remarks] 研究成果に新聞報道を掲載しました。乳がんリスク 遺伝子で推定（熊本）
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120518kumamoto.gif
• [Remarks] 研究成果に新聞報道を掲載しました。乳がんの発生 遺伝子で予測（沖縄）
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120606okinawa.gif
• [Remarks] 研究成果に新聞報道を掲載しました。
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120430nagasaki.gif
• [Remarks] 愛知県がんセンター研究所疫学・予防部ホームページ これまでの研究成果
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120518kumamoto.gif
• [Remarks] 愛知県がんセンター研究所疫学・予防部ホームページ これまでの研究成果
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120606okinawa.gif
• [Remarks] 愛知県がんセンター研究所疫学・予防部 ホームページ これまでの研究成果
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/01ekigaku/05-image/120430nagasaki.gif