Discovering the causes of three poorly understood cancers in Europe (DISCERN)

《辨别》的总体目标是了解欧洲三种鲜为人知的癌症--肾癌、胰腺癌和结直肠癌的病因，并帮助解释它们的地理分布，包括它们在中欧和东欧的高发病率。这将通过将大规模的欧洲生物信息库与最先进的分子图谱技术和机器学习方法相结合来实现，这些生物信息库包括基于人群的队列和肿瘤病例系列。特别是，识别中心将利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的详细地理空间和环境暴露信息，确定这三种癌症的潜在新原因风险因素，其中包括近900,000人。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在正常组织中促进因素。已确定的癌症风险因素的因果效应及其触发的细胞信号反应将使用一组干细胞和结肠、肾脏和胰腺3D器官进一步评估。SENCEN的结果将通过合作的患者和参与者组织传播给公民、患者和政策制定者。Discern将提供开发新的预防战略所需的关键证据基础，以解决欧洲日益增长的肾癌、胰腺癌和结直肠癌的负担。这项行动是癌症使命关于“了解”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 stateof-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".