Project 1:Improving Pancreatic Risk Assessment

项目概要/摘要： 我们的总体基础是，胰腺癌的发生有可识别的遗传倾向， 癌我们先前的工作已经确定了遗传因素在胰腺癌发生中的重要性。 癌的基因，并确定BRCA 2，PALB 2和ATM为家族性胰腺癌基因。然而，家族 80%的胰腺癌家族的聚集性仍然无法解释。这导致我们的整体翻译 目标;增加我们的科学证据基础，为遗传咨询和风险评估提供信息。 通过识别新的胰腺癌基因和识别高危人群， 大多数来自未来的化学预防试验和筛查早期，因此可能治愈， 胰腺肿瘤作为本项目的一部分，我们将1A）为了确定生殖系结构的贡献， 胰腺癌易感性的变异; 1B）鉴定新的胰腺癌易感性基因 通过单核苷酸变体和结构变体的组合分析：2）评估和 表征候选胰腺癌易感基因; 3A）确定个人或家族史 胰腺癌以外的其他癌症可以用来更好地估计胰腺癌的风险。 癌症3B）开发和验证增强的和临床实用的胰腺癌风险 纳入目标1、2和3A中确定的风险因素的分层模型。 总之，通过这个项目，我们希望继续解开遗传性胰腺炎的遗传基础。 癌症，并开发实用，强大和临床相关的工具，以指导精确的风险管理策略 为这些家庭。

Project Summary/Abstract: Our overall foundation is that there are identifiable genetic predispositions to the development of pancreatic cancer. Our prior work has established the importance of inherited factors in the development of pancreatic cancer, and identified BRCA2, PALB2 and ATM as familial pancreatic cancer genes. However, the familial clustering is still unexplained for 80% of pancreatic cancer families. This leads to our overall translational goals; to increase our scientific evidence base to inform genetic counseling and risk assessment of at-risk individuals by identifying new pancreatic cancer genes and to identify people at high-risk who would benefit most from future chemoprevention trials and efforts to screen for early, and therefore potentially curable, pancreatic neoplasia. As part of this project we will 1A) To determine the contribution of germline structural variants to pancreatic cancer susceptibility; 1B) To identify novel pancreatic cancer susceptibility genes through a combined analysis of single nucleotide variants and structural variants: 2) To evaluate and characterize candidate pancreatic cancer susceptibility genes; 3A) To determine if personal or family histories of cancers other than pancreatic cancer can be used to better estimate the risk of developing pancreatic cancer 3B) to develop and validate an enhanced and clinically practical pancreatic cancer risk stratification model incorporating risk factors identified in Aims 1, 2 and 3A. In summary, through this project we hope to continue to unravel the genetic basis of inherited pancreatic cancer and develop practical, robust and clinically relevant tools to guide precision risk-management strategies for these families.