Administrative Core

我们建议建立一个由流行病学家、统计学家、基础科学家 和临床科学家促进和追求与前列腺癌相关的基因组位点的彻底鉴定和表征。ELLIPSE（ELucidating Loci Involved in Prostate Cancer SuscEptibility）是一个翻译资助项目，由三个高度整合的项目组成。项目1旨在利用欧洲、非裔美国人、拉丁美洲人和日本人群中现有的和即将完成的前列腺癌GWAS来发现新的风险位点，并在现有的大型前列腺病例和对照组（PRACTICAL、BPC 3和MADCaP）中严格复制这些关联。这一扩大努力的一个主要重点是确定可能选择性地与晚期疾病和变异相关的基因座，这些基因座有助于疾病风险的种族差异。还将进行风险基因座的选择性精细定位，以全面表征相关等位基因座，利用Hapmap、选择性测序工作和1000基因组计划中常见变异的所有可用数据。项目2的重点是了解非蛋白质编码风险变体的基因。两个假设将系统地探讨使用各种各样的既定和新兴技术：风险位点港尚未检测到的成绩单（编码或非编码）和风险位点的监管元件。最后，在项目3中，我们建议通过基因-基因和基因-环境相互作用，研究这种新知识在前列腺癌易感性遗传基础上的潜力，以加强风险评估，重要的是，通过对癌症诊断和治疗的影响，或更新的癌症预防策略，为新的临床实践提供潜力。总体目标是发现驱动前列腺癌发病机制的途径，并评估其在临床决策中的作用。

We propose to establish a multidisciplinary team of epidemiologists, statisticians, basic scientists and clinician scientists to promote and pursue thorough identification and characterization of genomic loci associated with prostate cancer. ELLIPSE (ELucidating Loci Involved in Prostate cancer SuscEptibility) is a translational grant comprised of three highly integrated projects. Project 1 aims to take advantage of existing and shortly to be completed GWAS of prostate cancer in European, African American, Latino and Japanese populations to discover novel risk loci, and to rigorously replicate these associations in large existing consortia of prostate cases and controls (PRACTICAL, BPC3, and MADCaP). A major focus of this expanded effort is to identify loci that may selectively be associated with advanced disease and variants that contribute to ethnic difference in disease risk. Selective fine mapping of risk loci will also be performed to comprehensively characterize the relevant allelic locus, utilizing all available data on common variants from Hapmap, selective sequencing efforts, and from the 1000 Genome Project. Project 2 is focused on understanding the gene(s) that the non-protein coding risk variants are acting through. Two hypotheses will be systematically explored using a wide variety of established and emerging techniques: the risk loci harbor as yet undetected transcripts (either coding or non-coding) and the risk loci are regulatory elements. Finally, in Project 3 we propose to investigate the potential of this new knowledge on the genetic basis of prostate cancer susceptibility to enhance risk assessment, through gene-gene and gene-environment interactions, and importantly, to provide the potential for novel clinical practices through impacts on cancer diagnosis and treatment, or newer cancer prevention strategies. The overarching goal is to discover the pathways that drive prostate cancer pathogenesis and to assess their role in clinical decision making.