Familial Markers of Risk

我们的总体假设是，胰腺癌的发展存在可识别的遗传易感性。我们的总体转化目标是建立一个科学的证据基础，为家族性胰腺癌患者的遗传咨询和风险评估提供信息，识别具有特异性靶向治疗的遗传改变，并识别那些高危亲属，他们将从未来的化学预防试验和早期筛查中获益最多，因此有可能治愈的胰腺肿瘤。该项目的目标是进一步表征家族性胰腺癌的表型，确定胰腺癌的易感基因，并利用这些发现来改善患者及其家庭的临床风险评估。为了实现这些目标，我们将利用国家家族性胰腺肿瘤登记处的独特资源，其中有超过3900个胰腺癌家族，对家族性和散发性胰腺癌的病理进行详细分析，并对已建立的胰腺癌基因和允许基因与环境相互作用的环境风险因素进行外显率分析。此外，通过我们正在进行的来自100多个家族性胰腺癌家族的个体的全基因组和外显子组测序鉴定的候选基因将被评估，以确定其他胰腺癌易感基因。我们预计，我们的项目不仅将识别新的胰腺癌基因，而且还将量化与这些基因相关的胰腺癌风险，将这些发现转化为临床环境。

Our overall hypothesis is that there are identifiable genetic predispositions to the development of pancreatic cancer. Our overall translational goals are to develop a scientific evidence base to inform genetic counseling and risk assessment of familial pancreatic cancer patients, to identify genetic alterations that are specifically targetable therapeutically, and to identify those high risk relatives who would benefit most from future chemoprevention trials and efforts to screen for early, and therefore potentially curable, pancreatic neoplasia. The goals of this project are to characterize further the phenotype of familial pancreatic cancer, to identify pancreatic cancer susceptibility genes, and to use these discoveries to improve clinical risk assessment for patients and their families. To achieve these goals we will utilize the unique resource of the National Familial Pancreas Tumor Registry, with over 3,900 pancreatic cancer families to conduct detailed analysis of the pathology of both familial and sporadic pancreatic cancer as well as penetrance analysis for established pancreatic cancer genes and environmental risk factors that allow for gene by environment interaction. In addition, candidate genes identified through our ongoing whole genome and exome sequencing individuals from over 100 familial pancreatic cancer families will be evaluated to identify additional pancreatic cancer susceptibility genes. We anticipate that our project will not only identify new pancreatic cancer genes but also quantify the risk of pancreatic cancer associated with these genes translating these findings into the clinical setting.