Integrating epidemiologic, clinical, genomic and metabolomic profiles to predict pancreatic cancer risk in a multiethnic population

摘要 胰腺癌是一种高度致命的恶性肿瘤，在美国预后非常差。它有一个5- 一年存活率仅为9%，预计到2030年将成为第二大常见癌症死亡病例。 胰腺癌在不同种族/民族之间也有不成比例的负担，观察到更高的发病率。 在少数群体中，如非裔美国人、日裔美国人和夏威夷土著人。过去的预测 已经开发了一些模型来识别高危个体，并改进对这种疾病的早期检测。 然而，这些模型主要是由欧洲或亚洲血统的人设计的，并没有 在多民族人群中得到验证。此外，这些模型主要包括已知的流行病学风险因素。 而且只有几个人纳入了关于基因变异或健康状况的数据。因此，一种使用更多 细粒数据，如合并症/症状、基因组学和代谢组学，用于预测胰腺疾病 不存在跨越多个种族/民族的癌症。在这项研究中，我们试图应用一种综合的系统 使用多种族队列数据加强胰腺癌风险预测的生物学方法 (MEC)研究。MEC是一个由超过215,000名不同种族的人组成的长期预期队列， 拥有全面的生活方式、环境、临床和遗传数据。我们将使用现有资源中的数据 包括调查问卷中的流行病学危险因素、医疗保险中的临床健康状况 声称，来自大型血液样本生物仓库的基因数据，以及癌症发病率和死亡率信息 来自SEER癌症登记和州和国家死亡率数据库。我们还将产生新的新陈代谢 MEC参与者子集的数据。我们的具体目标是：1)确定临床条件的群组或模式 与胰腺癌风险相关；2)在多种族人群中验证现有预测模型，并 开发结合流行病学、临床和基因组数据的增强预测模型；3)确定 与多种族人群中的胰腺癌相关的代谢物；以及4)整合流行病学， 临床、基因组和代谢数据，以确定胰腺癌高危个体。由此产生的结果 这项研究有望阐明胰腺癌的病因机制，并提高对胰腺癌风险的预测。 异质种群。这将对改进早期检测策略具有重要意义 并减轻这种致命癌症的压倒性负担。

ABSTRACT Pancreatic cancer is a highly lethal malignancy that has a very poor prognosis in the United States. It has a 5- year survival rate of only 9% and is projected to become the second most common cancer death by 2030. Pancreatic cancer also has a disproportionate burden across race/ethnicity, with higher incidence rates observed among minority groups, such African Americans, Japanese Americans, and Native Hawaiians. Past prediction models have been developed to identify high-risk individuals and improve the earlier detection of this disease. However, these models were designed in individuals of primarily European or Asian ancestry and have not been validated in multiethnic populations. In addition, these models included mainly known epidemiologic risk factors and only a few incorporated data on genetic variants or health conditions. Thus, a model that employs more granular data, such as comorbidities/symptoms, genomics and metabolomics, for the prediction of pancreatic cancer across multiple races/ethnicities does not exist. In this study, we seek to apply an integrative systems biology approach to enhance the prediction of pancreatic cancer risk using data from the Multiethnic Cohort (MEC) Study. The MEC is a long-standing prospective cohort of over 215,000 racially diverse individuals that has comprehensive lifestyle, environmental, clinical, and genetic data. We will use data from existing resources of the MEC, including epidemiologic risk factors from questionnaires, clinical health conditions from Medicare claims, genetic data from a large biorepository of blood samples, and cancer incidence and mortality information from SEER Cancer registries and state and national mortality databases. We will also generate new metabolomic data for a subset of MEC participants. Our specific aims are: 1) to identify clusters or patterns of clinical conditions associated with pancreatic cancer risk; 2) to validate existing prediction models in a multiethnic population and develop an enhanced prediction model that incorporates epidemiologic, clinical and genomic data; 3) to identify metabolites associated with pancreatic cancer in a multiethnic population; and 4) to integrate epidemiologic, clinical, genomic and metabolomic data to identify individuals at high risk of pancreatic cancer. Results from this study are expected to elucidate etiologic mechanisms and improve the prediction of pancreatic cancer risk for heterogeneous populations. This will have significant implications for improving strategies for earlier detection and reducing the overwhelming burden of this fatal cancer.