Mechanism of multicentric carcinogenesis and prevention of the second cancer in the upper aerodigestive induced by cigarette smoking and alcohol drinking

• Project/Area Number: 18591467
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: MORITA Masaru Kyushu University, 大学病院, 講師 (30294937)
• Co-Investigator(Kenkyū-buntansha): 掛地 吉弘 九州大学, 医学研究院, 准教授 (80284488) ; 沖 英次 九州大学, 医学研究院, 非常勤講師 (70380392) ; 小山 倫浩 産業医科大学, 医学部, 助教授 (00309965) ; 江頭 明典 九州大学, 大学病院, 助手 (00419524)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: 食道癌 / 喫煙 / 飲酒 / p53 / FHIT / アルデヒド / 酸化的DNA損傷 / 食道外科学 / 癌抑制遺伝子

Research Abstract

食道癌の発生には喫煙・飲酒の関与が大きい。本研究にて、食道癌では癌抑制遺伝子p53の変異頻度が高く、中でもタバコ煙中のベンツピレンがもたらすトランスバージョン変異が多いことが明らかとなった。さらに癌抑制遺伝子FHITの低下が飲酒による食道多発癌の発生と関与していることが示唆された。一方、動物実験にてアルデヒド脱水素酵素の異常とアルデヒドの蓄積がアルコールによる発癌に関与していることが示唆された。

Research Products

• [Journal Article] The difference in p53 mutations between cancers of the upper and lower gastrointestinal tract (2009)
  • Author(s): Oki E, Zhao Y, Yoshida R, Egashira A, Ohgaki K, Morita M, Kakeji Y, Maehara Y.
  • Journal Title: Digestion 79 Suppl 1 Pages: 33-39
  • Peer Reviewed
• [Journal Article] Preoperative chemoradiotherapy for esophageal cancer : Factors associated with clinical response and postoperative complications (2009)
  • Author(s): Morita M, Masuda T, Okada S, Yoshinaga K, Saeki H, Tokunaga E, Endo K, Emi Y, Kakeji Y, Maehara Y.
  • Journal Title: Anticancer Res (印刷中)
  • Peer Reviewed
• [Journal Article] The difference in p53 mutations between cancers of the upper and lower gastrointestinal tract. (2009)
  • Author(s): Oki E, Morita M, Kakeji, et al
  • Journal Title: Digestion 79 Suppl1 Pages: 33-39
  • Peer Reviewed
• [Journal Article] Acute Lung Injury following an Esophagectomy for Esophageal Cancer : With special Reference to the Clinical Factors and Cytokine Levels of Peripheral Blood and Pleural Drainage Fluid (2008)
  • Author(s): Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N, Kakeji Y, Ichiki Y, Sugio K, Yasumoto K, Maehara Y
  • Journal Title: Dis Esophagus 21 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Successful treatment of tracheomediastinal fkistula after tracheal injury obtained during esophagectomy using pectoralis major muscle : a case report (2008)
  • Author(s): Koga T, Morita M, Nishida K, Oki E, Kakeji Y, Maehara Y
  • Journal Title: Esophagus 5 Pages: 41-44
  • Peer Reviewed
• [Journal Article] Advances in esophageal cancer surgery in Japan : An analysis of 1000 consecutive patients treated at a single institute (2008)
  • Author(s): Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N, Kakeji Y, Yamanaka T, Maehara Y
  • Journal Title: Surgery 143 Pages: 499-508
  • Peer Reviewed
• [Journal Article] Esophagectomy in patients 80 years of age and older with carcinoma of the thoracic esophagus (2008)
  • Author(s): Morita M, Egashira A, Yoshida R, Ikeda K, Ohgaki K, Sibahara K, Oki E, Sadanaga N, Kakeji Y, Maehara Y
  • Journal Title: J Gastroenterol 43 Pages: 345-351
  • NAID: 10021268598
  • Peer Reviewed
• [Journal Article] Expression of Cytochrome P450 in non-small cell lung cancer (2008)
  • Author(s): Oyama T, Sugio K, Isse T, Matsumoto A, Nose N, Uramoto H, Nozoe T, Morita M, Kagawa N, Osaki T, Muto M, Yasumoto K, Kawamoto T
  • Journal Title: Front Biosci 13 Pages: 5787-5793
  • Peer Reviewed
• [Journal Article] Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice (2008)
  • Author(s): Matsumoto A,Kawamoto T,Mutoh F,Isse T, Oyama T,Kitagawa K,Nakayama KI,Ichiba M
  • Journal Title: Pharmacogenet Genom 18 Pages: 847-852
  • Peer Reviewed
• [Journal Article] Increased frequencies of micronucleated reticulocytes and T-cell receptor mutation in Aldh2 knockout mice exposed to acetaldehyde (2008)
  • Author(s): Kunugita N, Isse T, Oyama T, Kitagawa K, Ogawa M, Yamaguchi T, Kinaga T, KawamotoT
  • Journal Title: J Toxicol Sci 33 Pages: 31-36
  • NAID: 110006596029
  • Peer Reviewed
• [Journal Article] Advances in esophageal cancer surgery in Japan : An analysis of 1OOO consecutive patients treated at a single institute (2008)
  • Author(s): Morita M, Oki E, Kakeji Y, et al
  • Journal Title: Surgery 143 Pages: 499-508
  • Peer Reviewed
• [Journal Article] Esophagectomy in patients 80 years of age and older with carcinoma of the thoracic esophagus (2008)
  • Author(s): Morita M, Oki E, Kakeji Y, et al
  • Journal Title: J Gastroenterol 43 Pages: 345-341
  • NAID: 10021268598
  • Peer Reviewed
• [Journal Article] Expression of Cytochrome P450 in non-small cell lung cancer (2008)
  • Author(s): Oyama T, Morita M, et al
  • Journal Title: Frontiers in Bioscience 13 Pages: 5787-5793
  • Peer Reviewed
• [Journal Article] Acute lung injury following an esophagectomy for esophageal cancer:With special reference to the clinical factors and cytokine levels of peripheral blood and pleural drainage fluid (2008)
  • Author(s): Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N, Kakeji Y, et. al.
  • Journal Title: Diseases of the Esophagus 21 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Expression of p53 and p21 and clinical response for hyperthermochemoradiotherapy in patients with squamous cell carcinoma of the esophagus (2007)
  • Author(s): Ishida M, Morita M, Saeki H, Ohga T, Sadanaga N, Watanabe M, Kakeji Y, Maehara Y
  • Journal Title: Anticancer Res 27 Pages: 3501-3506
  • Peer Reviewed
• [Journal Article] Promotoer hypermethylation and quantitative expression analysis of CDKN2A( p14^<ARF> and p16^<IK4a>)gene in esophageal squamous cell carcinoma (2007)
  • Author(s): Ito S, Ohga T, Saeki H, Watanabe M, KakejiY, Morita M, Yamada T, Maehara Y
  • Journal Title: Anticancer Res 27 Pages: 3345-3354
  • Peer Reviewed
• [Journal Article] Clinical significance of cytokeratin positive cells in bone marrow of gastric cancer patients (2007)
  • Author(s): Oki E, Kakeji Y, Baba H, Nishida K, Koga T, Tokunaga E, Egashira A, Ikeda K, Yoshida R, Yamamoto M, Morita M, Maehara Y
  • Journal Title: J Cancer Res Clin Oncol 133 Pages: 995-1000
  • Peer Reviewed
• [Journal Article] Salvage esophagectomy after definitive chemoradiotherapy for esophageal cancer (2007)
  • Author(s): Oki E, Morita M, Kakeji Y, Ikebe M, Sadanaga N, Egasira A, Nishida K, Koga T, Ohata M, Honboh T, Yamamoto M, Baba H, Maehara Y
  • Journal Title: Dis Esophagus 20 Pages: 301-304
  • Peer Reviewed
• [Journal Article] p53 gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis : results in Japan and comparisons with other countries (2007)
  • Author(s): Egashira A, Morita M, Kakeji Y, SadanagaN, Oki E, Honbo T, Ohta M, Maehara Y
  • Journal Title: Cancer Sci 98 Pages: 1152-1156
  • NAID: 10019539033
  • Peer Reviewed
• [Journal Article] Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice (2007)
  • Author(s): Oyama T, Isse T, Ogawa M, Muto M, UchiyamaI, Kawamoto T
  • Journal Title: Front Biosci 12 Pages: 1927-1934
  • Peer Reviewed
• [Journal Article] Cytochrome P450 expression(CYP)in non-small cell lung cancer (2007)
  • Author(s): Oyama T, Sugio K, Uramoto H, Kawamoto T, Kagawa N, Nadaf S, Carbone D, Yasumoto K
  • Journal Title: Front Biosci 12 Pages: 2299-2308
  • Peer Reviewed
• [Journal Article] Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis (2007)
  • Author(s): Oyama T, Sugio K, Uramoto H, Iwata T, Onitsuka T, Isse T, Nozoe T, Kagawa N, Yasumoto K, Kawamoto T
  • Journal Title: Front Biosci 12 Pages: 4497-4503
  • Peer Reviewed
• [Journal Article] A pilot study on subacute ethanol treatment of Aldh2 KO mice (2007)
  • Author(s): Oyama T, Kim YD, Isse T, Pham TTP, OgawaM, Yamaguchi T, Kinaga T, Yashima Y, KimH, Kawamoto T
  • Journal Title: J Toxicol Sci 32 Pages: 421-428
  • Peer Reviewed
• [Journal Article] Expression of p53 and p21 and clinical response for hyperthermochemoradiotherapy in patients with squamous cell carcinoma of the esophagus (2007)
  • Author(s): Ishida M, Morita M, Saeki H, Ohga T, Sadanaga N, Watanabe M, Kakeii Y, Maehara Y:
  • Journal Title: Anticancer Research 27 Pages: 3501-3506
  • Peer Reviewed
• [Journal Article] p53 gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis:Results in Japan and comparison with other countries (2007)
  • Author(s): Egashira A, Morita M, Kakeji Y, Sadanaga N, Oki E, Honbo T, Ohta M, Maehara Y
  • Journal Title: Cancer Science 98 Pages: 1152-1156
  • Peer Reviewed
• [Journal Article] Promotoer hypermethylation and quantitative expression analysis of CDKN2A(p14^<ARF> and p16^<INK4a>)gene in esophageal squamous cell carcmoma (2007)
  • Author(s): Ito S, Ohga T, Saeki H, Watanabe M, Kakeji Y, Morita M, Yamada T, Maehara Y
  • Journal Title: Anticancer Research 27 Pages: 3345-3354
  • Peer Reviewed
• [Journal Article] Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice. (2007)
  • Author(s): Oyama T, Isse T, Ogawa M, Muto M, Uchiyama I, Kawamoto T
  • Journal Title: Front Biosci 12 Pages: 1927-1934
• [Journal Article] Expressionof FHIT in esophageal epithelium and carcinoma : Reference to drinking, smoking and multicentric carcinogenesis (2006)
  • Author(s): Morita M, Oyama T, Nakata S, Ono K, SugayaM, Uramoto H, Yoshimatsu T, Hanagiri T, Sugio K, Yasumoto K
  • Journal Title: Anticancer Res 26 Pages: 2243-2248
  • Peer Reviewed
• [Journal Article] The metylation stqatus and protein expression of CDH1, p16INK4A, and fragile histidine triad in nonsmall cell lung carcinoma (2006)
  • Author(s): Nakata S, Sugio K, Uramoto H, Oyama T, Hananagiri T, Morita M, Yasumoto K
  • Journal Title: Cancer 106 Pages: 2190-2199
  • Peer Reviewed
• [Journal Article] Impact of loss of heterozygosity of encoding phosphate and tensin homolog on the prognosis of gastric cancer (2006)
  • Author(s): Oki E, Kakeji Y, Baba H, Tokunaga E, Nakamura T, Ueda N, Futatsugi M, Yamamoto M, Ikebe M, Maehara Y
  • Journal Title: J Gastroenterol Hepatol 21 Pages: 814-818
  • Peer Reviewed
• [Journal Article] Expression of FHIT in esophageal epithelium and carcinoma : Reference to drinking, smoking and multicentric carcinogenesis (2006)
  • Author(s): Morita M, Oyama T, Nakata S et al.
  • Journal Title: Anticancer Research 26 Pages: 2243-2248
• [Journal Article] 再発胸部食道癌の治療の実際 (2006)
  • Author(s): 森田勝, 掛地吉弘, 定永倫明, 他
  • Journal Title: 外科治療 95(3) Pages: 283-292
• [Journal Article] Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking (2006)
  • Author(s): Sugio K, Uramoto H, Ono K, Oyama T, Hanagiri T, Sugaya M, Ichiki Y, So T, Nakata S, Morita M, Yasumoto K
  • Journal Title: Br J Cancer 94(6) Pages: 896-903
• [Journal Article] The methylation status and protein expression of CDH1, p16(INK4A), and fragile histidine triad in nonsmall cell lung carcinoma : epigenetic silencing, clinical features, and prognostic significance (2006)
  • Author(s): Nakata S, Sugio K, Uramoto H, Oyam T, Hanagiri T, Morita M, Yasumoto K
  • Journal Title: Cancer 106(10) Pages: 2190-9
• [Journal Article] 食道癌におけるp53異常に注目した発癌分子機構の解析 (2006)
  • Author(s): 江頭明典, 森田勝, 池田圭介, 吉田倫太郎, 太田光彦, 本坊拓也, 沖英次, 織田信弥, 掛地吉弘, 前原喜彦
  • Journal Title: 第65回日本癌学会学術集会(proceedings) Pages: 140-140
• [Journal Article] Preoperative chemoradiotherapy for esophageal cancer : Factorsassociated with clinical response and postoperative complications
  • Author(s): Morita M, Kakeji Y, et al
  • Journal Title: Anticancer Res (印刷中)
  • Peer Reviewed
• [Presentation] The spectrum of p53 gene mutation in squamous cell carcinoma of the esophagus in Japan (2009)
  • Author(s): Saeki H, Morita M, Kakeji Y, et al
  • Organizer: 2009 Gastrointestinal Cancers Symposium (ASCO)
  • Place of Presentation: California
• [Presentation] Clinical significance of an esophagectomy in patients 75 years of age or older based on an analysis of 10000 perative cases with esophageal cancer (2008)
  • Author(s): Morita M, Yoshida R, Ohgaki K, Immura I, Shibahara K, Oki E, Sadanaga N, Kakeii Y, Maehara Y
  • Organizer: 2008 Gastrointestinal Cancers Symposium(ASCO)
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2008-01-25
• [Presentation] The spectrum of mutation and the frequency of allelic deletion of the p53 gene in gastrointestinal cancer : The difference between the upper and lower digestive tract (2008)
  • Author(s): Oki E, Kakeji Y, Ohgaki K, Shibahara K, Imamura I, Sadanaga N, Morita M, Maehara Y
  • Organizer: 2008 ASCO Gastrointestinal Cancers Symposium
  • Place of Presentation: Orlando,USA
• [Presentation] 消化器癌におけるp53変異解析とマイクロサテライト不安定性解析の診断的意義 (2008)
  • Author(s): 沖英次、掛地吉弘、趙岩、吉田倫太郎、岡田敏子、増田隆伸、大垣吉平、今村一郎、芝原幸太郎、定永倫明、森田勝、前原喜彦
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
• [Presentation] 食道癌におけるp53蛋白発現とp53遺伝子解析の意義 (2008)
  • Author(s): 沖英次、森田勝、安藤幸滋、杉山雅彦、増田隆伸、吉田倫太郎、今村一郎、大垣吉平、芝原幸太郎、定永倫明、掛地吉弘、前原喜彦
  • Organizer: 第62回日本食道学会学術集会
  • Place of Presentation: 東京
• [Presentation] 食道癌に対する術前化学・放射線療法の意義と今後の課題 (2008)
  • Author(s): 森田勝, 沖英次, 掛地吉弘, ほか
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
• [Presentation] Recent advance of surgical treatment for esophageal cancer in Japan : Anexperience of 1000 cases that underwent esophagectomy in a single institute (2007)
  • Author(s): Morita M, Okada S, Masuda T, Ikeda K, Yoshida R, Honboh T, Ohta M, Egashira A, Oki E, Sadanaga N, Kakeji Y, Maehara Y
  • Organizer: The 43rd Annual Meeting of American Society of Clinical Oncology
  • Place of Presentation: Chicago, USA
• [Presentation] 食道癌におけるp53異常の意義-遺伝子変異スペクトラムの解析と他臓器癌との比較 (2007)
  • Author(s): 沖英次、森田勝、江頭明典、岡田敏子、増田隆伸、池田圭介、吉田倫太郎、太田光彦、本坊拓也、定永倫明、掛地吉弘、前原喜彦
  • Organizer: 第61回日本食道学会学術集会
  • Place of Presentation: 横浜
• [Presentation] p53遺伝子変異スペクトラムからみた消化管癌における治療戦略 (2007)
  • Author(s): 沖英次、掛地吉弘、森田勝、吉田倫太郎、池田圭介、太田光彦、本坊拓也、江頭明典、定永倫明、前原喜彦
  • Organizer: 第62回日本消化器外科学会定期学術総会
  • Place of Presentation: 東京
• [Presentation] The difference p53 abnormalities between cancer of the upper and lower digestive tract (2007)
  • Author(s): Oki E, Kakeji Y, Ohgaki K, Shiotani S, Imamura I, Shibahara K, Yoshida R, Egashira A, Sadanaga N, Morita M, Maehara Y
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 呼吸器系組織におけるアセトアルデヒド感受性 (2007)
  • Author(s): 小山倫浩、一瀬豊日、PHAM Thi Thu Phuong、小川真規、山口哲右、木長健、八嶋康典、尾崎真一、松本明子、市場正良、欅田尚樹、川本俊弘
  • Organizer: 第80回日本産業衛生学会
  • Place of Presentation: 大阪
• [Presentation] Risk Factors for Esophageal Cancer and the Multiple Occurrence of Carcinoma in the Upper Aerodigestive Tract (2006)
  • Author(s): Morita M, Maehara Y
  • Organizer: 16th World Congress of the International Association of Surgeons and Gastroenterologists (and Oncologists)
  • Place of Presentation: Madrid, Spain
• [Presentation] 食道癌の発生における突然変異の蓄積とDNA修復異常に関する研究 (2006)
  • Author(s): 江頭明典、池田圭介、吉田倫太郎、小嶋綾、西田康二郎、古賀聡、徳永えり子、沖英次、織田信弥、森田勝、掛地吉弘、前原喜彦
  • Organizer: 第106回日本外科学会定期学術集会
  • Place of Presentation: 東京
• [Presentation] 食道癌におけるp53遺伝子変異及びタンパク質発現異常に関与する分子機構 (2006)
  • Author(s): 江頭明典、森田勝、池田圭介、吉田倫太郎、小嶋綾、西田康二郎、古賀聡、徳永えり子、沖英次、掛地吉弘、前原喜彦
  • Organizer: 第61回日本消化器外科学会定期学術総会
  • Place of Presentation: 横浜
• [Presentation] 食道癌におけるp53異常に注目した発癌分子機構の解析 (2006)
  • Author(s): 江頭明典、森田勝、池田圭介、吉田倫太郎、太田光彦、本坊拓也、沖英次、織田信弥、掛地吉弘、前原喜彦
  • Organizer: 第65回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] アセトアルデヒド皮下投与によるAldh2ノックアウトマウス表皮病変のp53 異常 (2006)
  • Author(s): 小山倫浩、一瀬豊日、山口哲右、小川真規、木長健、村上朋絵、奈良井理恵、松本明子、市場正良、八嶋康典、尾崎真一、欅田尚樹、村山留美子, 内山巌雄、川本俊弘
  • Organizer: 第79回日本産業衛生学会総会
  • Place of Presentation: 仙台
• [Book] 有効な症例「どんながんに有効なのか」食道の腫瘍(日本ハイパーサーミア学会編) (2008)
  • Author(s): 森田勝、定永倫明、前原喜彦
  • Publisher: ハイパーサーミアがん温熱療法ガイドブック
• [Book] 胃管による食道再建術Digestive Surgery Now No.2食道・胃外科標準手術(上西紀夫編) (2008)
  • Author(s): 森田勝、定永倫明、掛地吉弘、前原喜彦
  • Publisher: メジカルビュー社、東京
• [Book] 食道癌に対するsalvage手術の治療成績と妥当性-術前治療別にみた合併症と予後の比較検討- (2007)
  • Author(s): 森田勝、安藤幸滋、杉山雅彦、岡田敏子、増田隆伸、吉田倫太郎、今村一郎、大垣吉平、塩谷聡子、芝原幸太郎、沖英次、定永倫明、掛地吉弘、前原喜彦
  • Publisher: 癌の臨床
• [Remarks] 九州大学消化器・総合外科
  • URL: http://www.congre.co.jp/kyushu-u/surg2/
• [Remarks] 森田勝
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K0027661
• [Remarks] 九州大学消化器・総合外科
  • URL: http://www.congre.co.jp/kyushu-u/surg2/
• [Remarks] 森田勝
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K0027661