Discovering the causes of three poorly understood cancers in Europe - DISCERN

DISCERN的总体目标是了解欧洲三种鲜为人知的癌症的原因；肾癌、胰腺癌和结直肠癌，并有助于解释它们的地理分布，包括它们在中欧和东欧的高发病率。这将通过结合大规模的欧洲生物库来实现，这些生物库包括基于人群的队列和肿瘤病例系列，以及最先进的分子分析技术和机器学习方法。特别是，DISCERN将使用新的暴露组学和蛋白质组学扫描，以及来自16个大规模流行病学队列（包括近90万人）的详细地理空间和环境暴露信息，确定三种癌症的潜在新因果风险因素。它还将探索这些风险因素如何潜在地导致这些癌症类型的生物学机制，重点是使用深度测序，单细胞多组学和空间蛋白质组学研究正常组织中的促进因子。已确定的癌症风险因素及其引发的细胞信号反应的因果关系将通过干细胞和结肠、肾脏和胰腺3D类器官进行进一步评估。通过患者和参与组织的合作，将向公民、患者和决策者传播DISCERN结果。DISCERN将提供必要的关键证据基础，以制定新的预防战略，以应对欧洲日益增长的肾癌、胰腺癌和结直肠癌负担。这项行动是癌症使命“理解”项目集群的一部分。

The overall goal of DISCERN is to understand the causes of three poorly understood cancers in Europe; renal, pancreatic and colorectal cancer, and help to explain their geographical distribution, including their high incidence in central and eastern Europe. This will be achieved by combining large-scale European biorepositories comprising population-based cohorts and tumour case-series with state of-the-art molecular profiling techniques and machine learning approaches. In particular, DISCERN will identify potential new causal risk factors for the three cancers using novel exposomics and proteomics scans, as well detailed geospatial and environmental exposure information from 16 large-scale epidemiological cohortsincluding almost 900,000 individuals. It will also explore biological mechanisms on how these risk factors are potentially causing these cancer types with a focus on promoting factors in normal tissues using deep sequencing, single cell multi-omics and spatial proteomics. The causal effects of identified cancer risk factors and the cellular signalling responses they trigger will be further evaluated using a panel of stem cells and colon, renal and pancreatic 3D organoids. The results from DISCERN will be disseminated to citizens, patients and policy makers through collaborating patient and participant organizations. DISCERN will provide the critical evidence base required to develop new prevention strategies to tackle the growing burden of renal, pancreatic and colorectal cancer in Europe. This action is part of the Cancer Mission cluster of projects on "Understanding"