Analysis of relation between oxidative DNA repair genes,MUTYH and hepatocarcinogenesis

• Project/Area Number: 24590985
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: MIYANISHI Koji 札幌医科大学, 医学部, 講師 (60372819)
• Co-Investigator(Kenkyū-buntansha): JUNJI Kato 札幌医科大学, 医学部, 教授 (20244345) ; 田中 信悟 札幌医科大学, 医学部, 研究員 (60564024) ; 田中 信悟 札幌医科大学, 医学部, 研究員 (60561024)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 肝発癌危険因子 / 肝癌予防 / 酸化的DNA損傷 / 肝癌診断 / 酸化的DNA損傷修復遺伝子 / 肝癌 / 慢性肝炎 / 遺伝子修復酵素

Outline of Final Research Achievements

In one of MutYH SNPs (s3219487), the frequency of minor homo or hetero allele carrier in the HCC group significantly higher than that in HCC group. In addition, the expression of MUTYH mRNA in minor homo allele tended to be lower than that in major homo allele. Multivariate Cox regression analysis indicated that Age and the minor allele of this SNP in MUTYH factors were significantly associated with hepatocarcinogenesis independently. These results indicated that the minor hetero allele of this SNP in MUTYH could be a significant risk factor of liver carcinogenesis from CHC and could be a predictive marker of HCC development in CHC patients.

Research Products

• [Journal Article] Narrowband ultraviolet B phototherapy ameliorates acute graft-versus-host disease by a mechanism involving in vivo expansion of CD4+CD25+Foxp3+ regulatory T cells. (2014)
  • Author(s): Iyama S, Murase K, Sato T, Hashimoto A, Tatekoshi A, Horiguchi H, Kamihara Y, Ono K, Kikuchi S, Takada K, Kawano Y, Hayashi T, Miyanishi K, Sato Y, Takimoto R, Kobune M, Mori S, Kato J, Yamashita T, Kato J.
  • Journal Title: Int J Hematol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. (2013)
  • Author(s): Tanaka S, Miyanishi K, Kobune M, Kawano Y, Hoki T, Kubo T, Hayashi T, Sato T, Sato Y, Takimoto R, Kato J.
  • Journal Title: J Gastroenterol. Volume: 48(11) Issue: 11 Pages: 1249-58
  • DOI: 10.1007/s00535-012-0739-0
  • Peer Reviewed
• [Journal Article] Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes. (2013)
  • Author(s): Ishiwatari H, Sato Y, Murase K, Yoneda A, Fujita R, Nishita H, Birukawa NK, Hayashi T, Sato T, Miyanishi K, Takimoto R, Kobune M, Ota S, Kimura Y, Hirata K, Kato J, Niitsu Y.
  • Journal Title: Gut Volume: 62(9) Issue: 9 Pages: 1328-39
  • DOI: 10.1136/gutjnl-2011-301746
  • Peer Reviewed
• [Journal Article] A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker. (2013)
  • Author(s): Hirakawa M, Sato Y, Ohnuma H, Takayama T, Sagawa T, Nobuoka T, Harada K, Miyamoto H, Sato Y, Takahashi Y, Katsuki S, Hirayama M, Takahashi M, Ono M, Maeda M, Takada K, Hayashi T, Sato T, Miyanishi K, Takimoto R, Kobune M, Hirata K, Kato J
  • Journal Title: Cancer Chemother Pharmacol Volume: 71 Issue: 3 Pages: 789-797
  • DOI: 10.1007/s00280-013-2073-5
  • Peer Reviewed
• [Journal Article] Rapid on-site evaluation by endosonographer during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses. (2013)
  • Author(s): Hayashi T, Ishiwatari H, Yoshida M, Ono M, Sato T, Miyanishi K, Sato Y, Kobune M, Takimoto R, Mitsuhashi T, Asanuma H, Ogino J, Hasegawa T, Sonoda T, Kato J.
  • Journal Title: J Gastroenterol Hepatol. Volume: 28 Pages: 656-663
  • Peer Reviewed
• [Journal Article] Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes. (2013)
  • Author(s): Ishiwatari H, Sato Y, Murase K, Yoneda A, Fujita R, Nishita H, Birukawa NK, Hayashi T, Sato T, Miyanishi K, Takimoto R, Kobune M, Ota S, Kimura Y, Hirata K, Kato J, Niitsu Y.
  • Journal Title: Gut. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Targeting anticancer drug delivery to pancreatic cancer cells using a fucose-bound nanoparticle approach. (2012)
  • Author(s): Yoshida M, Takimoto R, Murase K, Sato Y, Hirakawa M, Tamura F, Sato T, Iyama S, Osuga T, Miyanishi K, Takada K, Hayashi T, Kobune M, Kato J.
  • Journal Title: PLoS One Volume: 7(7) Issue: 7 Pages: e39545-e39545
  • DOI: 10.1371/journal.pone.0039545
  • Peer Reviewed
• [Journal Article] Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox. (2012)
  • Author(s): Kikuchi S, Kobune M, Iyama S, Sato T, Murase K, Kawano Y, Takada K, Ono K, Kaneko Y, Miyanishi K, Sato Y, Hayashi T, Takimoto R, Kato J.
  • Journal Title: Free Radic Biol Med Volume: 23(6) Issue: 4 Pages: 548-550
  • DOI: 10.1016/j.freeradbiomed.2012.06.006
  • Peer Reviewed
• [Presentation] 酸化的DNA傷害修復酵素MUTYHのgenotypeによる肝発癌危険群の囲い込み (2014)
  • Author(s): 宮西浩嗣、河野豊、加藤淳二
  • Organizer: 日本肝臓学会大会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県・神戸市）
  • Year and Date: 2014-10-23
• [Presentation] C型慢性肝炎からの肝発癌における酸化的DNA傷害修復能の関与について (2014)
  • Author(s): 宮西浩嗣、小船雅義、加藤淳二
  • Organizer: 日本鉄バイオサイエンス学会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2014-09-06
• [Presentation] 鉄過剰を伴う慢性肝障害からの肝発癌における酸化的DNA傷害修復能の関与 (2014)
  • Author(s): 宮西浩嗣、保木寿文、加藤淳二
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ（東京都・千代田区）
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] 肝発癌における８－OHｄGの関与について (2013)
  • Author(s): 宮西浩嗣、田中信悟、小船雅義、加藤淳二
  • Organizer: 日本鉄バイオサイエンス学会
  • Place of Presentation: 東京
• [Presentation] NASHにおける鉄代謝異常の機序と肝発癌への関与の検討 (2012)
  • Author(s): 宮西浩嗣，田中慎悟，加藤淳二
  • Organizer: 第23回日本微量元素学会
  • Place of Presentation: 東京
• [Presentation] C型肝炎からの肝発癌における酸化剤DNA損傷修復遺伝子SNPの関与 (2012)
  • Author(s): 宮西浩嗣，小船雅義，加藤淳二
  • Organizer: JDDW2012
  • Place of Presentation: 兵庫