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8大最常见的癌症，也是第10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，观察到RCC的发病率急剧增加，其中一些最大的增加发生在中欧和美国的黑人人口中。除了吸烟、肥胖和高血压之外，这种疾病的许多病因仍有待确定。有越来越多的证据表明，遗传因素影响RCC的易感性，虽然这一假设已经研究不足。 我们最近完成了一项肾癌全基因组关联研究（GWAS），包括3，800例病例和8，500例对照。我们现在建议通过从一系列基于人群的病例对照和队列研究中纳入额外的3，800例病例和4，800例对照来扩展这项研究。通过NCI队列联盟倡议促进了队列研究的纳入。 除了其规模之外，我们的研究在以下几个方面是独一无二的：（1）将收集广泛的临床病理学信息和病例的生存率;（2）将对疾病发作和生存率进行遗传变异和RCC之间关联的全基因组分析;（3）将开发至少2，000例病例的生殖系DNA和肿瘤DNA和RNA的综合生物储存库;（4）将获得新鲜肾组织和肿瘤组织的全基因组基因表达谱，以补充从生殖系基因分型分析获得的结果。 公共卫生相关性：肾癌的发病率在过去几十年中一直在增加，并且当在晚期诊断时，该疾病的预后非常差（占美国病例的20%）。除了吸烟、肥胖和高血压之外，这种疾病的许多病因仍有待确定。我们建议研究与肾癌发病和生存相关的遗传因素，研究整个基因组的遗传变异，并将其与肿瘤组织的基因表达分析相结合。

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. PUBLIC HEALTH RELEVANCE: The incidence of kidney cancer has been increasing over the past decades and the disease has a very poor prognosis when diagnosed at an advanced stage (20% of the cases in the US). Apart from smoking, obesity and hypertension, much of the etiology of this disease remains to be identified. We propose to investigate genetic factors associated with kidney cancer onset and survival, looking at the genetic variants across the whole genome, and combining this with gene expression analysis of the tumor tissue.