Pooled genome-wide analysis of kidney cancer risk

描述（由申请人提供）：肾细胞癌（RCC）是美国第八大最常见的癌症，也是第十大最常见的癌症死亡形式，每年有超过34,000例病例和12,000例死亡。近几十年来，RCC的发病率急剧上升，其中中欧和美国黑人的发病率增幅最大。除了吸烟、肥胖和高血压外，这种疾病的大部分病因仍有待确定。越来越多的证据表明，遗传因素影响对RCC的易感性，尽管这一假设尚未得到充分研究。我们最近完成了一项RCC全基因组关联研究（GWAS），其中包括3800例病例和8500例对照。我们现在建议扩展这项研究，从一系列基于人群的病例对照和队列研究中纳入额外的3800例病例和4800例对照。通过NCI队列联盟倡议促进了队列研究的纳入。除了它的规模，我们的研究将在几个方面是独一无二的：(1)广泛的临床病理信息和病例的生存将被收集；(2)基因变异与RCC之间关系的全基因组分析将在发病和生存两方面进行；(3)建立至少2000例生殖系DNA、肿瘤DNA和RNA的综合生物信息库；(4)将获得新鲜肾组织和肿瘤组织的全基因组基因表达谱，以补充种系基因分型分析的结果。

DESCRIPTION (provided by applicant): Renal cell carcinoma (RCC) is the 8th most common cancer in the US and the 10th most common form of cancer death, with over 34,000 cases and 12,000 deaths each year. A sharp increase in the incidence of RCC was observed in recent decades with some of the greatest increases happening in Central Europe and among the black population in the US. Apart from smoking, obesity and hypertension, much of the etiology of this disease remains to be identified. There is increasing evidence that genetic factors influence susceptibility to RCC, although this hypothesis has been understudied. We have recently completed a genome-wide association study (GWAS) of RCC comprising 3,800 cases and 8,500 controls. We now propose to extend this study by incorporating an additional 3,800 cases and 4,800 controls from a series of population based case-control and cohort studies. Inclusion of cohort studies has been facilitated via the NCI cohort consortium initiative. In addition to its size, our study will be unique in several ways: (1) extensive clinicopathological information and survival of cases will be collected; (2) genome-wide analyses for the association between genetic variants and RCC will be conducted for both disease onset and survival; (3) a comprehensive biorepository of germline DNA and tumor DNA and RNA on at least 2,000 cases will be developed; (4) whole-genome gene expression profiling on fresh renal tissue and tumor tissue will be obtained to complement results obtained from the germline genotyping analyses.