Genome-wide analyses to identify genes involved in gastric cancer

全基因组分析以确定与胃癌有关的基因

• 批准号: 12212002
• 负责人: SASAZUKI Tekehiko
• 金额: $ 168.9万
• 依托单位: International Medical Center of Japan (2001-2004)Kyushu University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12212002/
• 关键词: gastric cancer; genome; polymorphism; linkage; association; SNP; microsatellite; 罹患同胞対; 連鎖; 相関; 全ゲノムスキャン; マイクロサテライトマーカー; SNPs; 多因子疾患; 罹患同胞対法; 全ゲノムスクリーニング; LOD値

Identification of genes predisposing to cancer is an essential step toward a better understanding of molecular events underlying tumorigenesis and for a more pertinent clinical management of patients. To search for regions of human genome containing gastric cancer-susceptibility genes, we did a genome-wide screen in 170 affected sibpairs using 392 microsatellite markers spanning the entire genome. Nonparametric linkage analysis of the entire data set identified four regions, Ip32, 2q33-q35, I1p13-p14 and 21q21, showing evidence for linkage with multipoint LOD score 【greater than or equal】1.18 (P 【less than or equal】0.01). The signal of linkage to 2q33-q35 increased to a multipoint and two-point LOD score 3.61 and 2.93, respectively in an analysis of a subgroup with proximal gastric cancer. Since chromosome 21q have been reported to show LOH frequently in gastric cancer in Japanese, we further analyzed 70 expressing genes on this candidate chromosome using sporadic cases by marker SNPs. We found unknown but the structure is related to HSP70 which is shown to be involved in carcinogenesis of several types of cancer. In addition, we genotyped SNPs in 41 candidate genes which have been suggested to be related to gastric carcinogenesis. We found significant association between ATM and female cases. According to the threshold theory of a multifactorial trait, heritability of female cases of gastric cancer might be higher than that of male cases. Taken together, STCH and ATM might be important target genes of further analyses to elucidate molecular mechanisms of gastric cancer pathogenesis.

鉴定易感癌症的基因是更好地理解肿瘤发生和更永久的患者临床管理的重要一步。为了搜索含有胃癌敏感性基因的人类基因组区域，我们使用横跨整个基因组的392个微卫星标记物在170个影响的Sibpair中进行了全基因组筛查。整个数据集的非参数链接分析确定了四个区域，即IP32、2Q33-Q35，I1P13-P14和21q21，显示了与多点LOD分数链接的证据[大于或等于] 1.18（P [p [小于或等于] 0.01）。与2q33-Q35连接的信号分别增加到多点和两点LOD得分3.61和2.93，这是对近端胃癌亚组的分析。由于据报道，据报道，据报道，抗胃癌日语中经常显示LOH，因此我们使用Marker SNP零星病例进一步分析了该候选染色体上的70个基因。我们发现未知，但该结构与HSP70有关，该HSP70与几种类型的癌症的致癌作用有关。此外，我们在41个候选基因中基因分型SNP，这些基因被认为与胃癌发生有关。我们发现ATM和女性病例之间存在显着关联。根据多因素性状的阈值理论，女性胃癌病例的遗传力可能高于男性病例。两者合计，STCH和ATM可能是进一步分析的重要靶基因，以阐明胃癌发病机理的分子机制。

项目成果

Oncogenic Ki-ras inhibits the expression of interferon-responsive genes through inhibition of STAT1 and STAT2

致癌 Ki-ras 通过抑制 STAT1 和 STAT2 来抑制干扰素反应基因的表达

• 发表时间: 2003
• 期刊: J Biol Chem. 278 (47)
• 作者: Klampfer L et al.

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