Comprehensive genome analysis for prostate cancer biomarkers

• Project/Area Number: 22390306
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: NAKAGAWA Hidewaki 独立行政法人理化学研究所, バイオマーカー探索開発チーム, チームリーダー (50361621)
• Co-Investigator(Renkei-kenkyūsha): KUBO Michiaki 独立行政法人理化学研究所, ゲノム医科学研究センター, 副センター長 (30442958) ; FURIHATA Mutsuo 高知大学, 医学部, 教授 (10209158) ; TAKATA Ryo 岩手医科大学, 医学部, 助教 (00438467) ; OGAWA Osamu 京都大学, 医学部, 教授 (90260611)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2010: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 前立腺癌 / ゲノム / GWAS / SNP / 前立腺がん / バイオマーカー / IRX4 / NKX3.1 / 8q24

Research Abstract

We performed follow-up Japanese GWAS (genome-wide association study) on additional Japanese DNA samples, and identified novel 4 loci associated with prostate cancer. The functional analysis of IRX4 and GGCX, which were identified by our GWAS, indicated novel mechanism of prostate carcinogenesis. We established a risk prediction model for Japanese prostate cancer and validated its consistency and accuracy.

Research Products

• [Journal Article] Prostate cancer genomics by high-throughput technologies: genome-wide association study and sequencing analysis (2013)
  • Author(s): Nakagawa H
  • Journal Title: Endocr Relat Cancer Volume: (in press)
• [Journal Article] Reproducibility, performance, and clinical utility of a genetic risk prediction model for prostate cancer in Japanese (2012)
  • Author(s): Akamatsu S, Takahashi A, Takata R, Kubo M, Inoue T, Morizono T, Tsunoda T, Kamatani N, Haiman CA, Wan P, Chen GK, Le Marchand L, Kolonel LN, Henderson BE, Fujioka T, Habuchi T, Nakamura Y, Ogawa O, Nakagawa H
  • Journal Title: PLoS ONE Volume: 7
• [Journal Article] Evaluating genetic risk for prostate cancer among Japanese and Latinos (2012)
  • Author(s): Cheng I, Chen GK, Nakagawa H, He J, Wan P, Laurie C, Shen J, Sheng X, Pooler LC, Crenshaw AT, Mirel DB, Takahashi A, Kubo K, Nakamura Y, Al Olama AA, Benlloch S, Donovan JL, Guy M, Hamdy FC, Kote-Jarai Z, Neal DE, Wilkens LR, Monroe KR, Stram DO, Muir K, Eeles RA, Easton DF, Kolonel LN, Henderson BE, Le Marchand L, Haiman CA
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 21 Pages: 2048-2058
• [Journal Article] Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese (2012)
  • Author(s): Akamatsu S, Takata R, Haiman CA, Takahashi A, Inoue T, Kubo M, Furihata M, Kamatani N, Inazawa J, Chen GK, Le Marchand L, Kolonel LN, Katoh T, Yamano Y, Yamakado M, Takahashi H, Yamada H, Egawa S, Fujioka T, Henderson BE, Habuchi T, Ogawa O, Nakamura Y, Nakagawa H
  • Journal Title: Nat Genet Volume: 44 Pages: 426-429
• [Journal Article] IRX4 at 5p15 suppresses prostate cancer growth through the interaction with vitamin D receptor, conferring prostate cancer susceptibility (2012)
  • Author(s): Nguyen HH, Takata R, Akamatsu S, Shigemizu D, Tsunoda T, Furihata M, Takahashi A, Kubo M, Kamatani N, Ogawa O, Fujioka T, Nakamura Y, Nakagawa H
  • Journal Title: Hum Mol Genet Volume: 21 Pages: 2076-2085
• [Journal Article] Prostate cancer genomics, biology, and risk assessment through genome-wide association studies (2012)
  • Author(s): Nakagawa H, Akamatsu S, Takata R, Takahashi A, Kubo M, and Nakamura Y
  • Journal Title: Cancer Sci Volume: 103 Pages: 607-613
• [Journal Article] がんバイオマーカー研究開発の課題と現状 (2012)
  • Author(s): 中川英刀
  • Journal Title: 日本臨床 Volume: 70(5) Pages: 743-748
• [Journal Article] 1. Prostate cancer genomics, biology, and risk assessment through genome-wide association studies (2012)
  • Author(s): 中川英刀, 他
  • Journal Title: Cancer Science Volume: 103 Issue: 4 Pages: 607-613
  • DOI: 10.1111/j.1349-7006.2011.02193.x
  • Peer Reviewed
• [Journal Article] IRX4 at 5p15 suppresses prostate cancer growth through the interaction with vitamin D receptor, conferring prostate cancer (2012)
  • Author(s): Ha Nguyen H, 他
  • Journal Title: Human Molecular Genetics Volume: 21 Issue: 9 Pages: 2076-2085
  • DOI: 10.1093/hmg/dds025
  • Peer Reviewed
• [Journal Article] Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese (2012)
  • Author(s): 赤松秀輔, 他
  • Journal Title: Nature Genetics Volume: 44 Issue: 4 Pages: 426-429
  • DOI: 10.1038/ng.1104
  • Peer Reviewed
• [Journal Article] Reproducibility, performance, and clinical utility of a genetic risk prediction model for prostate cancer in Japanese. (2012)
  • Author(s): 赤松秀輔
  • Journal Title: Plos One Volume: 7 Issue: 10 Pages: 46454-46454
  • DOI: 10.1371/journal.pone.0046454
  • Peer Reviewed
• [Journal Article] 前立腺癌 ゲノム解析による新規バイオマーカー探索 (2011)
  • Author(s): 中川英刀
  • Journal Title: 日本臨床 増刊号 Volume: 69(5) Pages: 145-149
• [Journal Article] Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility (2011)
  • Author(s): Suyoun Chung
  • Journal Title: Cancer Science Volume: 102 Pages: 245-252
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies five new prostate cancer susceptibility loci in the Japanese population. (2010)
  • Author(s): Ryo Takata
  • Journal Title: Nature Genetics Volume: 42 Pages: 751-754
  • Peer Reviewed
• [Journal Article] A functional variant in NKX3.1 associated with prostate cancer susceptibility down-regulates NKX3.1 expression. (2010)
  • Author(s): Shusuke Akamatsu
  • Journal Title: Human Molecular Genetics Volume: 19 Pages: 4265-4272
  • Peer Reviewed
• [Journal Article] 5αDH-DOC (5α-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer. (2010)
  • Author(s): Motohide Uemura
  • Journal Title: Cancer Science Volume: 101 Pages: 1897-1904
  • Peer Reviewed
• [Presentation] Prostate Cancer Genomics by Genome-wide Association Study (2012)
  • Organizer: Human Genome Variation and Complex Genome Analysis HGV2012
  • Place of Presentation: 上海
  • Year and Date: 2012-09-07
• [Presentation] Prostate Cancer Genomics, Biology, and Risk Estimation through Genome-Wide Association Study (2012)
  • Organizer: 日英個別化医療ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2012-02-14
• [Presentation] Prostate Cancer Genomics, Biology, and Risk Estimation through Genome-wide Association Study (2012)
  • Author(s): Nakagawa H
  • Organizer: 13th International Meeting on Human Genome Variation and Complex Genome Analysis
  • Place of Presentation: Shanghai, China
  • Invited
• [Presentation] Prostate cancer genomics by genome-wide association study (2011)
  • Author(s): 中川英刀
  • Organizer: 第42回高松宮妃癌研究シンポジウム
  • Place of Presentation: グランドパレスホテル(東京)(招待講演)
  • Year and Date: 2011-11-08
• [Presentation] A follow-up study of a GWAS identifies four novel prostate cancer susceptibility loci in the Japanese (2011)
  • Author(s): 赤松秀輔
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [Presentation] Risk estimation model with multiple common genetic variants for Japanese prostate cancer (2011)
  • Author(s): 高田亮
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [Presentation] Identifying of IRX4 at chromosome 5p15 as a novel tumor suppressor in prostate cancer (2011)
  • Author(s): Ha Hai Nguyen
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-03
• [Presentation] Functional Analysis of the Prostate Cancer Loci Identified by GWAS -NKX3.1 and 8q24- (2011)
  • Organizer: The Cancer Post Genome-Wide Association Initiative NCI
  • Place of Presentation: Bethesda, USA
  • Year and Date: 2011-01-13
• [Presentation] Functional Analysis of the Prostate Cancer Loci Identified by GWAS-NKX3.1 and 8q24- (2011)
  • Author(s): 中川英刀
  • Organizer: The Cancer Post GWAS Initiative Meeting (NIH)
  • Place of Presentation: 米国・Bethesda
  • Year and Date: 2011-01-13
• [Presentation] Prostate Cancer Genomics by Genome-wide Association Study (2011)
  • Organizer: 高松宮妃国際シンポジウム
  • Place of Presentation: 東京
• [Presentation] A follow-up study of a GWAS identifies four novel prostate cancer susceptibility loci in the Japanese (2011)
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Risk estimation model with multiple common genetic variants for Japanese prostate cancer (2011)
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Identifying IRX4 at chromosome 5p15 as a novel tumor suppressor in prostate cancer (2011)
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Genome-wide association study identifies multiple susceptibility loci for prostate cancer in a Japanese population (2010)
  • Organizer: 10^(th) Annual Meeting of East Asian Union of Human Genetics Societies
  • Place of Presentation: 済南
  • Year and Date: 2010-10-09
• [Presentation] Functional variants in NKX3.1 Conferring Prostate Cancer Susceptibility by Down-regulating NKX3.1 Expression (2010)
  • Author(s): 赤松秀輔
  • Organizer: 日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Genome-wide association study identifies multiple new susceptibility loci for prostate cancer in the Japanese population (2010)
  • Author(s): 高田亮
  • Organizer: 日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] 前立腺癌のゲノミックス:ゲノム解析からの前立腺癌の理解 (2010)
  • Organizer: 第98回日本泌尿器科学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-29
• [Presentation] 前立腺癌のgenomics:ゲノム解析からの前立腺癌の理解 (2010)
  • Author(s): 中川英刀
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-29
• [Presentation] Functional variants in NKX3.1 Conferring Prostate Cancer Susceptibility by Down-regulating NKX3.1 Expression (2010)
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
• [Presentation] Genome-wide association study identifies multiple new susceptibility loci for prostate cancer in the Japanese population (2010)
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
• [Remarks] 2012年10月5日 遺伝子多型を組み合わせた日本人のための前立腺がんリスク診断法を開発
• [Remarks] 2012年2月24日 前立腺がんの発症に関わる4つの遺伝子多型を新たに発見
• [Remarks]
  • URL: http://www.riken.go.jp/r-world/info/release/press/2010/100802/index.html
• [Patent(Industrial Property Rights)] 一塩基多型に基づく前立腺癌の検査方法 (2011)
  • Inventor(s): 中川英刀、久保充明、高橋篤、赤松秀輔、高田亮、小川修、中村祐輔
  • Industrial Property Number: 2011-019051
  • Filing Date: 2011-01-31
• [Patent(Industrial Property Rights)] 一塩基多型に基づく前立腺癌の検査方法 (2011)
  • Inventor(s): 中川英刀, 他
  • Industrial Property Rights Holder: 理化学研究所, 他
  • Industrial Property Number: 2011-001905
  • Filing Date: 2011-01-31