2000 Fiscal Year Annual Research Report

胃がん発症に関与する遺伝子の解明

Research Project

Project/Area Number	12212002
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (C)
Research Institution	Kyushu University
Principal Investigator	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
Co-Investigator(Kenkyū-buntansha)	松野正紀東北大学, 医学部, 教授 (80004737) 佐々木泰史札幌医科大学, 医学部, 助手 (70322328) 伊東文生札幌医科大学, 医学部, 講師 (90223180) 磨伊正義金沢大学, がん研究所, 教授 (80092807) 三輪晃一金沢大学, 医学部, 教授 (80019968)
Keywords	胃がん / 罹患同胞対法 / 全ゲノムスクリーニング / 連鎖解析 / 相関解析 / LOD値 / マイクロサテライトマーカー
Research Abstract	胃がんの発症に関与する遺伝子を同定する目的で、胃がん罹患同胞対を対象に400以上のマイクロサテライトマーカーを用いた全ゲノムスクリーニングによる連鎖解析を行った。罹患同胞対はこれまでに96組が収集され、うち87組に対する統計遺伝学的解析が終了した。この結果、以下の知見が得られた。 1)11番染色体11p12(D11S925近傍)、11q13(D11S937近傍)、11q24(D11S935近傍)に多点解析でLOD値がそれぞれ1.3、1.8、1.2を示す領域を同定した。また、これらの領域は単点解析でLOD値2.9(P=0.002)、3.5(P=0.0003)、1.5(P=0.07)を示した。 2)21番染色体21q11(D215S1256近傍)に多点解析でLOD値が2.2を示す領域を同定した。また、D21S263近傍に単点解析でLOD値2.1(P=0.02)を領域を同定した。 3)診断時年齢が5才以下の同胞対を解析することにより、上記1)の11番染色体11q13(D11S937近傍)に多点解析、単点解析でLOD値がそれぞれ3.0、3.6(P=0.0006)を示す領域を同定した。以上の結果より、日本人に多い胃がん発症に関連する遺伝子が11番染色体、21番染色体に存在する可能性が示唆された。今後これらの領域を狭め遺伝子を同定するために統計学的相関解析を行うが、この解析に必要な若年発症孤発胃がん症例の収集を昨年度と同様に継続し、これまでに183検体(診断時平均年齢41.7才、男女比が1:1)が収集された。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Wataya M et al.: "Comparative analysis of HLA restriction and cytokine production of hepatitis B surface antigen-specific T cells from low-and high-antibody responders in vaccinated humans."Journal of Human Genetics. (in press). (2001)
[Publications] Hamaguchi K et al.: "Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes : HLAB and-DRB1 alleles are primarily associated with the disease in Japanese"Tissue Antigens. 55. 10-16 (2000)
[Publications] Fukui Y et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact."Proceedings of the National Academy of Sciences, USA. 97. 13760-13765 (2000)
[Publications] Toh H et al.: "Magnitude of structural changes of the T-cell receptor binding regions determine the strength of T-cell antagonism : molecular dynamics simulations of HLA-DR4 (DRB1*0405) complexed with analogue peptide."Protein Engineering. 13. 423-429 (2000)
[Publications] Ries S et al.: "Opposing effects of Ras on p53 : transcriptional activation of mdm2 and induction of p19^<ARF>."Cell. 103. 321-330 (2000)
[Publications] Shirasawa S et al.: "Rnx deficiency results in congenital central hypoventilation."Nature Genetics. 24. 287-290 (2000)
[Publications] Kawamura K et al.: "HLA-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice."Journal of Clinical Investigation. 105. 977-984 (2000)
[Publications] Baba I et al.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Research. 60. 6886-6889 (2000)
[Publications] Kobari M et al.: "Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer."Br.J.Surg.. 87. 43-48 (2000)
[Publications] Takahashi Y et al.: "α-difluolomethylornithine induced apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in a human gastric cancer model."Int.J.Cancer. 85. 243-247 (2000)
[Publications] Tajima Y et al.: "Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma : analysis of 240 surgically resected tumors."Cancer. 88. 1285-1293 (2000)
[Publications] Kondo S et al.: "Regional and para-aortic lymphadenectomy in radical surgery for advanced gallbladder carcinoma."Bri.J.Surg.. 87. 418-422 (2000)
[Publications] Nakamura K et al.: "Morphometric analysis of regional lymph nodes with and witout metastasis from early gastric carcinoma."Cancer. 88. 2438-2442 (2000)
[Publications] Kodera Y: "Clinical Relevance of telomerase activity in primary gastric lymphoma."Gastric Cancer. 3. 57-62 (2000)
[Publications] Yamamoto H et al.: "Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma."Cancer Res.. 59. 3313-3316 (1999)
[Publications] Shimoyama Y et al.: "Biochemical characterization and functional analysis of two type II classic cadherins, cadherin-6 and -14, and comparison with E-cadherin."J.Biol Chem.. 274. 11987-11994 (1999)
[Publications] Sugimachi K et al.: "The S-1 gastrointestinal cancer study group : An early phase II study of oral S-1, a newly developed 5-fluoroucil derivative for treating patients with advanced and recurrent gastrointestinal cancers."Oncology. 57. 202-210 (1999)
[Publications] Xiangming C et al.: "Cooccurence of reduced expression of alpha-catenin and overexpression of p53 is a predictor of lymph node metastasis in early gastric cancer."Oncology. 57. 131-137 (1999)

2000 Fiscal Year Annual Research Report

胃がん発症に関与する遺伝子の解明

Principal Investigator

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

Research Products

[Publications] Wataya M et al.: "Comparative analysis of HLA restriction and cytokine production of hepatitis B surface antigen-specific T cells from low-and high-antibody responders in vaccinated humans."Journal of Human Genetics. (in press). (2001)

[Publications] Hamaguchi K et al.: "Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes : HLAB and-DRB1 alleles are primarily associated with the disease in Japanese"Tissue Antigens. 55. 10-16 (2000)

[Publications] Fukui Y et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact."Proceedings of the National Academy of Sciences, USA. 97. 13760-13765 (2000)

[Publications] Toh H et al.: "Magnitude of structural changes of the T-cell receptor binding regions determine the strength of T-cell antagonism : molecular dynamics simulations of HLA-DR4 (DRB1*0405) complexed with analogue peptide."Protein Engineering. 13. 423-429 (2000)

[Publications] Ries S et al.: "Opposing effects of Ras on p53 : transcriptional activation of mdm2 and induction of p19^<ARF>."Cell. 103. 321-330 (2000)

[Publications] Shirasawa S et al.: "Rnx deficiency results in congenital central hypoventilation."Nature Genetics. 24. 287-290 (2000)

[Publications] Kawamura K et al.: "HLA-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice."Journal of Clinical Investigation. 105. 977-984 (2000)

[Publications] Baba I et al.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Research. 60. 6886-6889 (2000)

[Publications] Kobari M et al.: "Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer."Br.J.Surg.. 87. 43-48 (2000)

[Publications] Takahashi Y et al.: "α-difluolomethylornithine induced apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in a human gastric cancer model."Int.J.Cancer. 85. 243-247 (2000)

[Publications] Tajima Y et al.: "Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma : analysis of 240 surgically resected tumors."Cancer. 88. 1285-1293 (2000)

[Publications] Kondo S et al.: "Regional and para-aortic lymphadenectomy in radical surgery for advanced gallbladder carcinoma."Bri.J.Surg.. 87. 418-422 (2000)

[Publications] Nakamura K et al.: "Morphometric analysis of regional lymph nodes with and witout metastasis from early gastric carcinoma."Cancer. 88. 2438-2442 (2000)

[Publications] Kodera Y: "Clinical Relevance of telomerase activity in primary gastric lymphoma."Gastric Cancer. 3. 57-62 (2000)

[Publications] Yamamoto H et al.: "Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma."Cancer Res.. 59. 3313-3316 (1999)

[Publications] Shimoyama Y et al.: "Biochemical characterization and functional analysis of two type II classic cadherins, cadherin-6 and -14, and comparison with E-cadherin."J.Biol Chem.. 274. 11987-11994 (1999)

[Publications] Sugimachi K et al.: "The S-1 gastrointestinal cancer study group : An early phase II study of oral S-1, a newly developed 5-fluoroucil derivative for treating patients with advanced and recurrent gastrointestinal cancers."Oncology. 57. 202-210 (1999)

[Publications] Xiangming C et al.: "Cooccurence of reduced expression of alpha-catenin and overexpression of p53 is a predictor of lymph node metastasis in early gastric cancer."Oncology. 57. 131-137 (1999)

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)