1998 Fiscal Year Annual Research Report

頻度の高い非遺伝的腫瘍の遺伝的感受性と遺伝子多型性

Research Project

Project/Area Number	10470056
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	椙村春彦浜松医科大学, 医学部, 教授 (00196742)
Co-Investigator(Kenkyū-buntansha)	若井建志名古屋大学, 医学部, 助手 (50270989) 河野隆志国立がんセンター, 研究員 (80280783) 田中正光浜松医科大学, 医学部, 助手 (20291396)
Keywords	hOGG1 / 肺癌 / 多型 / 分子疫学 / 80H-グアニン
Research Abstract	今年度ますます頻度が増加すると思われる肺癌について、比較的commonなDNA障害とおもわれる、酸化的DNA障害の代表的なものである、8-OH付加体の形成を修復するhOGG1という酵素多型に焦点をしぼった。対象として、すでに、Cyp1A1多型と肺癌リスクとのあいだに興味深い関係を見い出しており、一定の検出力をもつと期待される沖縄の症例対照DNAをもちいた。hOGG1にはいくつかの多型が存在するが、exon7のSer326Cysをとりあげた。この部位は機能部位に近く大腸菌のcomplimentation assayではCys型の蛋白はSer型の約7分の1しか機能しない。したがって、Cys alleleがより癌の感受性を上昇させることが期待される。結果は241例の肺癌と197例の病院対照郡を用いて、Cys/Cys型の個体が、Ser/SerおよびSer/Cys型に比べて、 1. 扁平上皮癌でのみ有為なリスクの増加をみとめた[オッズ比3.01(95%confidence interval,1.33-6.83)〕 2. 他の組織型やまた、Ser/Ser型をreferenceにした場合はいずれも有為なリスクの上昇はみとめなかった。 3. この多型には人種差があり、Cys alleleはMelanesian,Hungarians,Australian Caucasianでは、Chinese(Jinagsu),japanese(Tokyo),Micornesian(Yap)よりも頻度が低かった。喫煙に関連があるといわれる組織型の一部で、有為な危険度をみとめたことは、喫煙中のoxyradicalが肺癌の発癌に関与するという仮説やまた、肺癌患者やヘビースモーカーの肺組織中に80H付加体をより多く検出できるという報告に矛盾しないものであり、この多型と肺癌感受性との関連を示唆するものであった。小細胞癌については差がでなかったが症例数の少なさのためと考えている。しかし、相対的危険度数値からみて、この多型はCyp1A1ほどは肺癌のリスクとなっていない可能性もあり過大に評価するべきではない。オキシラディカルの疾病との関与はより頻度の高い胃炎などにおいても指摘されており、萎縮性胃炎や近年その終末像という見方もなり立ちうる胃癌などについても検討が必要である。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Kohno,Takashi: "Genetic polymorphisms and alternative splicing of the hOGG1 gene,that involved in the repair of 8-hydroxyguanine in damaged DNA." Oncogene. 16. 3219-3226 (1998)
[Publications] Sugimura H: "Association of lle462Val(exon7)polymorphism of cytochrome P4501Al lung cancer in the Asian population: Further evidence from a case-control study in Okinawa" Cancer Epidemiology,Biomarkers & Prevention. 7. 413-417 (1998)
[Publications] Yasuhisa Naito: "Collagen and elastin syntehsis by desmoid tumor in vitro." Pathology International. 48. 603-610 (1998)
[Publications] Hiroyuki Uchida: "Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum." Jpn.J.Cancer Res.89. 299-306 (1998)
[Publications] Tanaka M: "Interaction of EphB2-tyrosine kinase receptor and its ligand conveys dors alization signal in Xenopus laevis development." Oncogene. 17. 1509-1516 (1998)
[Publications] Kazuhiko Yasumi: "Tansforming Growth Factor beta type 2 receptor(TGFbRII)mutation in gastric lymphoma without mutator phenotype." Pathology International. 48. 134-137 (1998)
[Publications] Rong-Jun Guo: "Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer" Carcinogenesis. 19. 1539-1544 (1998)
[Publications] Kazuya Shinmura: "Infrequent mutations of the hOGG1 gene,that is involved in the excision of 8-hydroxyguanine in damaged DNA,in human gastric cancer." Japanese Journal of Cancer Research. 89. 825-8 (1998)
[Publications] Kiyokawa E: "Evidence That DOCK180 Up-regulates Signals from the Crkll-p130(Cas)Complex." J Biol Chem. 8;273(38). 24479-24484 (1998)
[Publications] Shinmura K: "RER phenotype and its associated mutations in familial gastric cancer." Carcinogenesis. 19. 247-251 (1998)
[Publications] Hiroyuki Konno: "Antitumor effect of a neutralizing antibody to vascular endotehlial growth factor on liver metastasis of endocrine neoplasm." Japanese Journal of Cancer Research. 89. 933-939
[Publications] Ying Wang: "Mutational analysis of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability." Japanese Journal of Cancer Research. 89. 1284-1291 (1998)
[Publications] Kiyokawa E: "Activation of Rac1 by a Crk SH3-bunding protein,DOCK180." Genes Dev. 12(21). 3331-3336 (1998)
[Publications] Toshifumi Nakamura: "Hepatocellular Carcinoma in Type 1a Glycogen Storage Disease with Identification of a Glucose-6-Phosphatase Gene Mutation in One Family" Journal of Gastroenterology and Hepatology. (in press).
[Publications] Isogaki J: "Microsatellite instability and K-ras mutations in gastric adenomas,with reference to associated gastric cancers." Cancer Detection and Prevention. (in press).
[Publications] Shinmura K: "Familial gastric cancer: clinicopathological characteristics,RER phenotyp and germline p53 and E-cadherin mutations" Carcinogenesis. (in press).

1998 Fiscal Year Annual Research Report

頻度の高い非遺伝的腫瘍の遺伝的感受性と遺伝子多型性

Principal Investigator

椙村 春彦 浜松医科大学, 医学部, 教授 (00196742)

Research Products

[Publications] Kohno,Takashi: "Genetic polymorphisms and alternative splicing of the hOGG1 gene,that involved in the repair of 8-hydroxyguanine in damaged DNA." Oncogene. 16. 3219-3226 (1998)

[Publications] Sugimura H: "Association of lle462Val(exon7)polymorphism of cytochrome P4501Al lung cancer in the Asian population: Further evidence from a case-control study in Okinawa" Cancer Epidemiology,Biomarkers & Prevention. 7. 413-417 (1998)

[Publications] Yasuhisa Naito: "Collagen and elastin syntehsis by desmoid tumor in vitro." Pathology International. 48. 603-610 (1998)

[Publications] Hiroyuki Uchida: "Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum." Jpn.J.Cancer Res.89. 299-306 (1998)

[Publications] Tanaka M: "Interaction of EphB2-tyrosine kinase receptor and its ligand conveys dors alization signal in Xenopus laevis development." Oncogene. 17. 1509-1516 (1998)

[Publications] Kazuhiko Yasumi: "Tansforming Growth Factor beta type 2 receptor(TGFbRII)mutation in gastric lymphoma without mutator phenotype." Pathology International. 48. 134-137 (1998)

[Publications] Rong-Jun Guo: "Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer" Carcinogenesis. 19. 1539-1544 (1998)

[Publications] Kazuya Shinmura: "Infrequent mutations of the hOGG1 gene,that is involved in the excision of 8-hydroxyguanine in damaged DNA,in human gastric cancer." Japanese Journal of Cancer Research. 89. 825-8 (1998)

[Publications] Kiyokawa E: "Evidence That DOCK180 Up-regulates Signals from the Crkll-p130(Cas)Complex." J Biol Chem. 8;273(38). 24479-24484 (1998)

[Publications] Shinmura K: "RER phenotype and its associated mutations in familial gastric cancer." Carcinogenesis. 19. 247-251 (1998)

[Publications] Hiroyuki Konno: "Antitumor effect of a neutralizing antibody to vascular endotehlial growth factor on liver metastasis of endocrine neoplasm." Japanese Journal of Cancer Research. 89. 933-939

[Publications] Ying Wang: "Mutational analysis of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability." Japanese Journal of Cancer Research. 89. 1284-1291 (1998)

[Publications] Kiyokawa E: "Activation of Rac1 by a Crk SH3-bunding protein,DOCK180." Genes Dev. 12(21). 3331-3336 (1998)

[Publications] Toshifumi Nakamura: "Hepatocellular Carcinoma in Type 1a Glycogen Storage Disease with Identification of a Glucose-6-Phosphatase Gene Mutation in One Family" Journal of Gastroenterology and Hepatology. (in press).

[Publications] Isogaki J: "Microsatellite instability and K-ras mutations in gastric adenomas,with reference to associated gastric cancers." Cancer Detection and Prevention. (in press).

[Publications] Shinmura K: "Familial gastric cancer: clinicopathological characteristics,RER phenotyp and germline p53 and E-cadherin mutations" Carcinogenesis. (in press).

椙村春彦浜松医科大学, 医学部, 教授 (00196742)