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

DISCERN的总体目标是了解欧洲三种知之甚少的癌症的原因：肾癌、胰腺癌和结直肠癌，并帮助解释它们的地理分布，包括中欧和东欧的高发病率。这将通过将包括基于人群的队列和肿瘤病例系列的大规模欧洲生物库与最先进的分子分析技术和机器学习方法相结合来实现。特别是，DISCERN将使用新的基因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，确定这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来促进正常组织中的因素。已确定的癌症风险因素及其引发的细胞信号传导反应的因果影响将使用一组干细胞和结肠，肾脏和胰腺3D类器官进行进一步评估。DISCERN的结果将通过合作的患者和参与组织传播给公民、患者和决策者。DISCERN将提供制定新的预防策略所需的关键证据基础，以应对欧洲日益增长的肾癌、胰腺癌和结直肠癌负担。这一行动是癌症使命“理解”项目组的一部分。

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"