Molecular epidemiology study on genetic factors of persistent Inflammation and their involvement in lifestyle-associated diseases

• Project/Area Number: 18390190
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Radiation Effects Research Foundation
• Principal Investigator: HAYASHI Tomonori Radiation Effects Research Foundation, 放射線生物学/分子疫学部, 免疫学研究室長 (70333549)
• Co-Investigator(Kenkyū-buntansha): KUSUNOKI Yoichiro 財団法人放射線影響研究所, 放射線生物学/分子疫学部, 部長代理 (60333548) ; TOKUNOU Masahide 財団法人放射線影響研究所, 放射線生物学/分子疫学部, 来所研究員 (40288824) ; NAKACHI Kei 財団法人放射線影響研究所, プロジェクト代表研究者 (00142117)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,200,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥2,700,000); Fiscal Year 2008: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2007: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2006: ¥5,500,000 (Direct Cost: ¥5,500,000)
• Keywords: 生活習慣病 / サイトカイン / 遺伝子多型 / 分子疫学 / ゲノム / 放射線 / 炎症 / ケモカイン

Research Abstract

原爆被爆者コーホート研究を用いて、持続性炎症とそれに関連する遺伝子の多型との関係を調べ、原爆被爆者のがん発生への遺伝的要因と環境要因の影響について研究を行った結果、胃および肝がんリスクは原爆放射線量に伴い有意に増加するが、それらのリスクは炎症関連遺伝子IL-10の遺伝子型により大きく影響を受けていることを見出した。特に放射線に被曝した時、これらのがんのリスクが高い人々を同定することが可能になると考えられた。

Research Products

• [Journal Article] Caspase-independent cell death without generation of reactive oxygen species in irradiated MOLT-4 human leukemia cells (2009)
  • Author(s): Yoshida K, Kubo Y, Kusunoki Y, Morishita Y, Nagamura H, Hayashi I, Kyoizumi S, Seyama T, Nakachi K, Hayashi T
  • Journal Title: Clin Immunol 255 Pages: 61-68
  • Peer Reviewed
• [Journal Article] Protective effect of vitamin C on oxidative stress: a randomized controlled trial (2008)
  • Author(s): Sasazuki S, Hayashi T, Nakachi K, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S
  • Journal Title: Int J Vitam Nutr Res 78 Pages: 121-128
  • Peer Reviewed
• [Journal Article] TNF-alpha-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells (2008)
  • Author(s): Suganuma M, Yamaguchi K, Ono Y, Matsumoto H, Hayashi T, Ogawa T, Imai K, Kuzuhara T, Nishizono A, Fujiki H
  • Journal Title: Int J Cancer 123 Pages: 117-122
  • Peer Reviewed
• [Journal Article] Cytolethal distending toxin induces caspase-dependent and -independent cell death in MOLT-4 cells (2008)
  • Author(s): Ohara M, Hayashi T, Kusunoki Y, Nakachi K, Fujiwara T, Komatsuzawa H, Sugai M
  • Journal Title: Infect Immun. 76 Pages: 4783-4791
  • Peer Reviewed
• [Journal Article] 放射線被曝と発がんリスクに及ぼす遺伝的要因 (2008)
  • Author(s): 吉田健吾、林 奉権、森下ゆかり、長村浩子、牧 真由美、空 美佐江、今井一枝、楠 洋一郎、中地 敬
  • Journal Title: 長崎医学会雑誌 83 Pages: 254-258
  • Peer Reviewed
• [Journal Article] Sixty years of follow-up of Hiroshima and Nagasaki survivors: current progress in molecular epidemiology studies (2008)
  • Author(s): Nakachi K, Hayashi T, Hamatani K, Eguchi H, Kusunoki Y
  • Journal Title: Mutat Res 659 Pages: 109-117
  • Peer Reviewed
• [Journal Article] Long-lasting alterations of the immune system by ionizing radiation exposure: Implications for disease development among atomic bomb survivors (2008)
  • Author(s): Kusunoki Y, Hayashi T
  • Journal Title: Int J Radiat Biol 84 Pages: 1-14
  • Peer Reviewed
• [Journal Article] Long-lasting alterations of the immune system by ionizing radiation exposure : Implications for disease development among atomic bomb (2008)
  • Author(s): Kusunoki Y
  • Journal Title: Int J Radiat Biol 84 Pages: 1-14
  • Peer Reviewed
• [Journal Article] Sixty years of follow-up of Hiroshima and Nagasaki survivors : Current progress in molecular epidemiology studies (2008)
  • Author(s): Nakachi K
  • Journal Title: Mutat Res 659 Pages: 109-117
  • Peer Reviewed
• [Journal Article] TNF-alpha-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells (2008)
  • Author(s): Suganuma M
  • Journal Title: Int J Cancer 123 Pages: 117-122
  • Peer Reviewed
• [Journal Article] Cytolethal distending toxin induces caspase-dependent and -independent cell death in MOLT-4 cells (2008)
  • Author(s): Ohara M
  • Journal Title: Infect Immun 76 Pages: 4783-4791
  • Peer Reviewed
• [Journal Article] Genetic factors underlying risks of radiation-associated cancers (2008)
  • Author(s): Yoshida K
  • Journal Title: Nagasaki Med J 83 Pages: 254-258
• [Journal Article] Long-lasting alterations of the immune system by ionizing radiation exposure : Implications for disease development among atomic bomb survivors (2008)
  • Author(s): Kusunoki Y
  • Journal Title: Int J Radiat Biol 84 Pages: 1-14
  • Peer Reviewed
• [Journal Article] Sixty Years of Follow-up of Hiroshima and Nagasaki Survivors : Current Progress in Molecular Epidemiology Studies (2008)
  • Author(s): Nakachi K
  • Journal Title: Mutat Res (In press)
  • Peer Reviewed
• [Journal Article] High-throughput spectrophotometric assay of reactive oxygen species in serum (2007)
  • Author(s): Hayashi I, Morishita Y, Imai K, Nakamura M, Nakachi K, Hayashi T
  • Journal Title: Mutat Res. 631 Pages: 55-61
  • Peer Reviewed
• [Journal Article] Risks of radiation-related diabetes differ among atomic-bomb survivors with different HLA class II haplotypes (2007)
  • Author(s): Hayashi T, Fujiwara S, Kusunoki Y, Nakashima E, Suzuki G, MacPhee DG, Kyoizumi S
  • Journal Title: Immunobiology of the Human MHC Pages: 340-343
• [Journal Article] High-throughput spectrophotometric assay of reactive oxygen species in serum (2007)
  • Author(s): Hayashi I
  • Journal Title: Mutat Res 631(1) Pages: 55-61
  • Peer Reviewed
• [Journal Article] Radiation sensitivity and genomic instability in the hematopoietic system : Frequencies of micronucleated reticulocytes in whole-body X-irradiated BALB/c and C57BL/6 mice (2007)
  • Author(s): Hamasaki K
  • Journal Title: Cancer Sci 98(12) Pages: 1840-1844
  • Peer Reviewed
• [Journal Article] Risks of radiation-related diabetes differ among atomic-bomb survivors with different HLA class II haplotypes (2007)
  • Author(s): Hayashi T
  • Journal Title: Immunobiology of the Human MHC 2007 Pages: 340-343
• [Journal Article] High-throughput spectrophotometric assay of reactive oxygen species in serum (2007)
  • Author(s): Hayashi I.
  • Journal Title: Mutat Res (in press)
• [Journal Article] 原爆放射線のヒト免疫応答に及ぼす影響(第24報) : CD43の発現を指標としたメモリーCD4 T細胞サブセットの測定 (2006)
  • Author(s): 楠 洋一郎、山岡美佳、久保美子、濱崎幹也、林 奉権、京泉誠之、中地 敬
  • Journal Title: 長崎医学会雑誌 81 Pages: 350-353
• [Journal Article] 原爆放射線のヒト免疫応答におよぼす影響 第23報 : 炎症マーカーの長期的上昇 (2006)
  • Author(s): 森下ゆかり、林 奉権、長村浩子、久保美子、笠置文善、楠 洋一郎、箱田雅之、京泉誠之、藤原佐枝子、中地 敬
  • Journal Title: 広島医学 59 Pages: 413-416
• [Journal Article] 原爆放射線のヒト免疫応答におよぼす影響 第22報 : CD4 T細胞サブセット比率の被ばく放射線量依存性低下は長崎原爆被爆者においても明らかに認められる (2006)
  • Author(s): 久保美子、楠 洋一郎、箱田雅之、笠置文善、山岡美佳、空 美佐江、井上真弓、松浦信介、林 奉権、京泉誠之、藤原佐枝子、赤星正純、中地 敬
  • Journal Title: 広島医学 59 Pages: 409-412
• [Journal Article] Levels of antibodies to microorganisms implicated in atherosclerosis and of C-reactive protein among atomic bomb survivors (2006)
  • Author(s): Hakoda M, Kasagi F, Kusunoki Y, Matsuura S, Hayashi T, Kyoizumi S, Akahoshi M, Suzuki G, Kodama K, Fujiwara S
  • Journal Title: Radiat Res 166 Pages: 360-366
  • Peer Reviewed
• [Journal Article] Levels of antibodies to microorganisms implicated in atherosclierosis and of C-reactive protein among atomic bomb survivors. (2006)
  • Author(s): Hakoda M.
  • Journal Title: Radiat Res 166・2 Pages: 360-366
• [Journal Article] 原爆放射線のヒト免疫応答におよぼす影響(第22報) : CD4T細胞サブセット比率の被ばく放射線量依存性低下は長崎原爆被爆者においても明らかに認められる (2006)
  • Author(s): 久保 美子
  • Journal Title: 広島医学 59・4 Pages: 409-412
• [Journal Article] 原爆放射線のヒト免疫応答におよぼす影響(第23報) : 炎症マーカーの長期的上昇 (2006)
  • Author(s): 森下 ゆかり
  • Journal Title: 広島医学 59・44 Pages: 413-416
• [Journal Article] 原爆放射線のヒト免疫応答に及ぼす影響(第24報) : CD43の発現を指標としたメモリーCD4T細胞サブセットの測定 (2006)
  • Author(s): 楠 洋一郎
  • Journal Title: 長崎医学会雑誌 81 Pages: 350-353
• [Presentation] Individuals at high risk of stomach cancer among atomic-bomb survivors identified in RERF immunogenome study (2009)
  • Author(s): Hayashi T
  • Organizer: 36th Annual Meeting of the European Environmental Mutagen Society
  • Place of Presentation: Prague, Czech
• [Presentation] ゲノム解析に基づく原爆被爆者の発がん感受性の探索 (2008)
  • Author(s): 吉田健吾
  • Organizer: 第33回 中国地区放射線影響研究会
  • Place of Presentation: 広島
  • Year and Date: 2008-07-30
• [Presentation] 一般住民コーホートで観察された喫煙の生体影響と生活習慣病の分子疫学研究 (2008)
  • Author(s): 今井一枝
  • Organizer: 平成19年度喫煙科学研究財団研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-24
• [Presentation] 放射線被曝と発癌リスクに及ぼす遺伝的要因 (2008)
  • Author(s): 吉田健吾
  • Organizer: 第49回 原子爆弾後障害研究会
  • Place of Presentation: 長崎
  • Year and Date: 2008-06-08
• [Presentation] 原爆被爆における免疫ゲノム解析 : IL-10ハプロタイプと放射線と腸型とびまん性の胃がんリスク (2008)
  • Author(s): 林 奉権
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] 胃がんリスクとIL-10ハプロタイプとの関連およびそれに対する放射線被曝の影響 (2008)
  • Author(s): 林 奉権
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 腸型胃癌とびまん性胃癌のリスクとIL-10ハプロタイプとの関係およびそれに対する放射線被曝の影響 (2008)
  • Author(s): 林 奉権
  • Organizer: 第17回日本組織適合性学会
  • Place of Presentation: 大阪
• [Presentation] Aging-associated elevation of inflammatory markers was accelerated among atomic-bomb survivors (2008)
  • Author(s): Hayashi T
  • Organizer: US-Japan Cooperative Medical Science Program, Immunology Board: Immunosenescence Workshop
  • Place of Presentation: San Francisco, California, US
• [Presentation] Effects of IL-10 and IL-6 gene polymorphisms and atomic-bomb radiation exposure on gastric cancer risk (2008)
  • Author(s): Hayashi T
  • Organizer: IARC-EACR-AACR-ECNIS Symposium
  • Place of Presentation: Lyon, France
• [Presentation] Relationship of intestinal- and diffuse-type gastric cancer risks to IL-10 haplotypes and effects of radiation exposure on the relationship (2008)
  • Author(s): Hayashi T
  • Organizer: 20th European Association for Cancer Research
  • Place of Presentation: Lyon, France
• [Presentation] Mouse strain difference in sensitivity to radiation-induced genomic instability persisting in vivo for prolonged periods after irradiation (2008)
  • Author(s): Kusunoki Y
  • Organizer: The International Ataxia-Telangiectasia Workshop
  • Place of Presentation: Otsu, Japan
• [Presentation] Relationship of intestinal- and diffuse-type gastric cancer risks to IL-10 haplotypes and effects of radiation exposure on the relationship (2008)
  • Author(s): Hayashi T
  • Organizer: The 20th European Association for Cancer Research
  • Place of Presentation: Lyon, France
• [Presentation] Polymorphic NBN and EGFR genes affect cancer development among atomic-bomb survivors in Hiroshima and Nagasaki (2008)
  • Author(s): Yoshida K
  • Organizer: Cold Spring Harbor Laboratory Meeting : Molecular Genetics of Aging
  • Place of Presentation: New York, New York, USA
• [Presentation] 発がんリスクを高める喫煙がおよぼす炎症・免疫関連生体指標への影響 (2008)
  • Author(s): 今井一枝
  • Organizer: 第15回 がん予防大会2008
  • Place of Presentation: 福岡
• [Presentation] 腸型胃癌とびまん性胃癌のリスクとIL-10ハプロタイプとの関係およびそれに対する放射線被曝の影響 (2008)
  • Author(s): 林奉権
  • Organizer: 第17回 日本組織適合性学会
  • Place of Presentation: 大阪
• [Presentation] 原爆被爆生存者におけるHLA遺伝子型頻度分布 (2008)
  • Author(s): 長村浩子
  • Organizer: 第17回 日本組織適合性学会
  • Place of Presentation: 大阪
• [Presentation] 胃がんリスクとIL-10ハプロタイプとの関連およびそれに対する放射線被曝の影響 (2008)
  • Author(s): 林奉権
  • Organizer: 第67回 日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 原爆被爆における免疫ゲノム解析:IL-10ハプロタイプと放射線と腸型とびまん性の胃がんリスク (2008)
  • Author(s): 林奉権
  • Organizer: 第38回 日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] 炎症関連サイトカイン遺伝子多型と原爆放射線被曝が胃がんリスクに及ぼす影響 (2007)
  • Author(s): 林 奉権
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Effects of inflammation-related gene polymorphisms and atomic-bomb radiation exposure on gastric cancer risk (2007)
  • Author(s): Hayashi T
  • Organizer: The 12th World Congress on Advances in Oncology and the 10th International Symposium on Molecular Medicine and Cancer Chemoprevention Symposium
  • Place of Presentation: Crete, Greece
• [Presentation] Elevated levels of plasma reactive oxygen species and inflammatory markers among atomic-bomb survivors (2007)
  • Author(s): Morishita Y
  • Organizer: Joint ESTP/IFSTP Congress of Toxicologic Pathology 2007
  • Place of Presentation: Basel, Switzerland
• [Presentation] Effects of inflammation-related cytokine gene polymorphisms on gastric cancer risk among atomic bomb survivors (2007)
  • Author(s): Nagamura H
  • Organizer: Joint ESTP/IFSTP Congress of Toxicologic Pathology 2007
  • Place of Presentation: Basel, Switzerland
• [Presentation] Gastric cancer risks among atomic-bomb survivors differ by HLA class I genotype (2007)
  • Author(s): Hayashi T
  • Organizer: Joint ESTP/IFSTP Congress of Toxicologic Pathology 2007
  • Place of Presentation: Basel, Switzerland
• [Presentation] IL-10遺伝子多型と原爆放射線被曝の胃がん発症リスクに及ぼす影響 (2007)
  • Author(s): 森下ゆかり
  • Organizer: 第16回日本組織適合性学会
  • Place of Presentation: 京都
• [Presentation] Effects of inflammation-related gene polymorphisms and atomic-bomb radiation exposure on gastric cancer risk (2007)
  • Author(s): Hayashi T
  • Organizer: 13th International Congress of Radiation Research
  • Place of Presentation: San Francisco, California, USA
• [Presentation] Hiroshima 60 years : Monitoring of survivors-Current progress in molecular epidemiology studies (2007)
  • Author(s): Nakachi K
  • Organizer: 5th International Conference on Environmental Mutagens in Human Populations
  • Place of Presentation: Antalya, Turkey
• [Presentation] IL-10遺伝子多型と原爆放射線被曝の胃がん発症リスクに及ぼす影響 (2007)
  • Author(s): 森下ゆかり
  • Organizer: 第16回 日本組織適合性学会
  • Place of Presentation: 京都
• [Presentation] Gastric cancer risks among atomic-bomb survivors differ by HLA class I genotype (2007)
  • Author(s): Hayashi T
  • Organizer: Joint ESTP/IFSTP Congress of Toxicologic Pathology
  • Place of Presentation: Basel, Switzerland
• [Presentation] Effects of inflammation-related cytokine gene polymorphisms on gastric cancer risk among atomic bomb survivors (2007)
  • Author(s): Nagamura H
  • Organizer: Joint ESTP/IFSTP Congress of Toxicologic Pathology
  • Place of Presentation: Basel, Switzerland
• [Presentation] Elevated levels of plasma reactive oxygen species and inflammatory markers among atomic-bomb survivors (2007)
  • Author(s): Morishita Y
  • Organizer: Joint ESTP/IFSTP Congress of Toxicologic Pathology
  • Place of Presentation: Basel, Switzerland
• [Presentation] 炎症およびがん関連免疫におよぼす喫煙の影響 (2007)
  • Author(s): 今井一枝
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 炎症関連サイトカイン遺伝子多型と原爆放射線被曝が胃がんリスクに及ぼす影響 (2007)
  • Author(s): 林 奉権
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] 炎症関連遺伝子多型と原爆放射線被曝の胃がん発症リスクに及ぼす影響 (2006)
  • Author(s): 林 奉権
  • Organizer: 第16回広島がんセミナー国際シンポジウム
  • Place of Presentation: 広島
  • Year and Date: 2006-10-22
• [Presentation] 炎症関連遺伝子多型と原爆放射線被曝の胃がん発症リスクに及ぼす影響 (2006)
  • Author(s): 林 奉権
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Book] T-cell homeostasis and inflammatory response among a-bomb survivors. In : Low-Dose Radiation Exposures and BioDefense System. (Ed by Tanaka S, Fujikawa F, Oghiso Y.) (2006)
  • Author(s): Kusunoki Y.
  • Total Pages: 117
  • Publisher: The Institute for Environmental Sciences
• [Remarks]
  • URL: http://www.rerf.jp/library/scidata/cr_e/cr0701.htm
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