Analysis of polymorphisms of breast cancer and prostate cancer risk-associated genetic variations by using semiconductor-based next-gen sequencings

• Project/Area Number: 15K08720
• 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: Chiba Cancer Center (Research Institute)
• Principal Investigator: Nakamura Yohko 千葉県がんセンター(研究所), がん予防センター, 主席研究員 (60260254)
• Co-Investigator(Kenkyū-buntansha): 三上 春夫 千葉県がんセンター(研究所), がん予防センター, 部長 (10332355)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 乳がん / 前立腺がん / エクソーム解析 / がん関連遺伝子 / 次世代シークエンサー

Outline of Final Research Achievements

We conducted next-generation sequencing to identify potential genetic variants associated with the incidence of cancer in a cohort study containing 8,100 healthy individuals. We sequenced the genome of a cohort of individuals, including 40 breast cancer cases and 28 prostate cancer cases, and observed the recurrence of several functional non-synonymous SNVs with significant associations to the risk of cancer in 2 genes. Sanger sequencing also confirmed the recurrence of these mutations. We also analyzed polymorphisms of breast cancer related genes in the 40 breast cancer and found five amino acid substitutions in six of those 40 cases. Those substitutions were results of the presence of four known and one unknown SNPs. The risk variants characterized in this study can be a useful predictive tool for the early detection, diagnosis and monitoring of cancer. Analysis of those functional risk alleles may highlight the underlying mechanisms leading to oncogenesis in these risk populations.

Research Products

• [Journal Article] A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study. (2018)
  • Author(s): Hiroko Nakagawa-Senda, Tsuyoshi Hachiya, Atsushi Shimizu, Satoyo Hosono, Isao Oze, Miki, Watanabe, Keitaro Matsuo, Hidemi Ito, Megumi Hara, Yuichiro Nishida, Kaori Endoh, Kiyonori Kuriki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Yora Nindita, Rie Ibusuki, Sadao Suzuki, Akihiro Hosono, et al.
  • Journal Title: Scientific Report Volume: 8 Issue: 1 Pages: 1493-1493
  • DOI: 10.1038/s41598-018-19914-w
  • Peer Reviewed / Open Access
• [Journal Article] Genomic analysis–integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway (2017)
  • Author(s): Li Yuanyuan、Ohira Miki、Zhou Yong、Xiong Teng、Luo Wen、Yang Chao、Li Xiangchun、Gao Zhibo、Zhou Rui、Nakamura Yohko、Kamijo Takehiko、Kaneko Yasuhiko、Taketani Takeshi、Ueyama Junichi、Tajiri Tatsuro、Zhang Hongyan、Wang Jian、Yang Huanming、Yin Ye、Nakagawara Akira
  • Journal Title: Oncotarget Volume: 8 Issue: 34 Pages: 56684-56697
  • DOI: 10.18632/oncotarget.18079
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Variants of <i>RAMP2</i> and <i>CLR</i> are Associated with Stroke (2017)
  • Author(s): Koyama T, Kuriyama N, Ozaki E, Matsui D, Watanabe I, Takeshita W, Iwai K, Watanabe Y, Nakatochi M, Shimanoe C, Tanaka K, Oze I, Ito H, Uemura H, Katsuura-Kamano S, Ibusuki R, Shimoshikiryo I, Takashima N, Kadota A, Kawai S, Sasakabe T, Okada R, Hishida A, Naito M, Mikami H, Nakamura Y, Wakai K. et.al.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 24 Issue: 12 Pages: 1267-1281
  • DOI: 10.5551/jat.41517
  • NAID: 130006235289
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access
• [Journal Article] Effects of novel small compounds targeting TrkB on neuronal cell survival and depression-like behavior. (2016)
  • Author(s): Fukuda M, Takatori A, Nakamura Y, Suganami A, Hoshino T, Tamura Y, Nakagawara A
  • Journal Title: Neurochemistry International Volume: 97 Pages: 42-48
  • DOI: 10.1016/j.neuint.2016.04.017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells (2016)
  • Author(s): Mohammad Sazzadul Islam, Yasutoshi Tatsumi, Ryo Takano, Tomoki Yokochi, Jesmin Akter, Toshinori Ozaki, Yohko Nakamura, Miki Ohira, and Akira Nakagawara
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 478 Issue: 1 Pages: 81-86
  • DOI: 10.1016/j.bbrc.2016.07.089
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma. (2016)
  • Author(s): Satoh S, Takatori A, Ogura A, Kohashi K, Souzaki R, Kinoshita Y, Taguchi T, Hossain MS, Ohira M, Nakamura Y, Nakagawara A.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 32682-32682
  • DOI: 10.1038/srep32682
  • Peer Reviewed / Open Access
• [Journal Article] BMCC1, which is an interacting partner of BCL2, attenuates AKT activity, accompanied by apoptosis. (2015)
  • Author(s): Tatsumi Y, Takano R, Islam MS, Yokochi T, Itami M, Nakamura Y, Nakagawara A.
  • Journal Title: Cell Death Dis. Volume: 6 Issue: 1 Pages: e1607-e1607
  • DOI: 10.1038/cddis.2014.568
  • Peer Reviewed / Open Access
• [Journal Article] Functional interplay between MYCN, NCYM and OCT4 promotes aggressiveness of human neuroblastomas. (2015)
  • Author(s): Kaneko Y, Suenaga Y, Islam SM, Matsumoto D, Nakamura Y, Ohira M, Yokoi S, Nakagawara A.
  • Journal Title: Cancer Sci. Volume: 10 Issue: 7 Pages: 12677-12677
  • DOI: 10.1111/cas.12677
  • Peer Reviewed / Open Access
• [Presentation] 前向きコホート研究による胃がん高リスク群でのアミノ酸変化を伴う多型の解析 (2017)
  • Author(s): 中村洋子、滝口伸浩、三上春夫、永瀬浩喜
  • Organizer: 第26回日本癌病態治療研究会
• [Presentation] 千葉利根川水系におけるがんの高罹患率の原因究明 (2017)
  • Author(s): 中村洋子、高山喜美子、三上春夫、永瀬浩喜
  • Organizer: 日本がん登録協議会第26回学術集会
• [Presentation] 前向きコホート研究によるがんの高リスク群でのアミノ酸変化を伴う多型の解析 (2017)
  • Author(s): 中村洋子、巽康年、奥村和弘、高取敦志、丸喜明、横井左奈、大平美紀、鍋谷圭宏、深沢賢、片山稔、三上春夫、永瀬浩喜
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 血清中の微量元素含有量を用いた新たながんスクリーニング法の開発に関する研究 (2017)
  • Author(s): 三上春夫、宮城洋平、中村洋子、永瀬浩喜
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 前向きコホート研究による胃がん高リスク群でのアミノ酸変化を伴う多型の解析 (2016)
  • Author(s): 滝口伸浩、中村洋子、三上春夫、永瀬浩喜
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-20
• [Presentation] Analysis of non-synonymous genetic variations associated with cancer risk by a prospective cohort study (2016)
  • Author(s): Yohko Nakamura, Yoshiaki Maru, Yasutoshi Tatsumi, Kazuhiro Okumura, Sana Yokoi, Miki Ohira,, Yoshihiro Nabeya, Satoshi Fukasawa, Jin Katayama Hiroki Nagase, Haruo Mikami
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 半導体次世代シークエンサーによるリスク集団特異的がん関連遺伝子多型解析 (2015)
  • Author(s): 中村洋子、丸喜明、巽康年、横井左奈、大平美紀,、中村友紀、高山喜美子、稲田潤子、片山稔、永瀬浩喜、三上春夫
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2015-10-29
• [Presentation] 半導体次世代シークエンサーによるリスク集団特異的がん関連遺伝子多型解析 (2015)
  • Author(s): 中村洋子、丸喜明、巽康年、横井左奈、大平美紀、中村友紀、高山喜美子、稲田潤子、田中尚武、山本尚人、鍋谷圭宏、滝口伸浩、植田健、片山稔、永瀬浩喜、三上春夫
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2015-10-14
• [Presentation] Analysis of cancer risk-associated genetic variations by using semiconductor-based next-gen sequencings in J-MICC study (2015)
  • Author(s): Yohko Nakamura, Yoshiaki Maru, Yasutoshi Tatsumi, Sana Yokoi, Miki Ohira, Yuki Nakamura, Kimiko Takayama, Junko Inada, Jin Katayama, Hiroki Nagase, Haruo Mikami
  • Organizer: 第74回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Remarks] 千葉県がんセンター研究所
  • URL: https://www.pref.chiba.lg.jp/gan/kenkyujo/index.html
• [Remarks] 千葉県がんセンター研究所Facebook
  • URL: https://m.facebook.com/CCCRI.chiba.gan.kenkyujo
• [Remarks] 千葉県がんセンター研究所
  • URL: http://www.pref.chiba.lg.jp/gan/kenkyujo/
• [Remarks] 千葉県がんセンター研究所
  • URL: http://www.pref.chiba.lg.jp/gan/kenkyujo/index.html