ECOGENETICS OF PANCREATIC CANCER: A NATIONAL REGISTRY OF FAMILIES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。长期目标是确定一种破坏性的、常见的恶性肿瘤（即外分泌胰腺腺癌）的生态遗传（基因-环境）起源，这一提议的工作是一个开始。攻击计划取决于对似乎患有过量癌症的家庭进行跨学科研究的行之有效的策略，在这种情况下，是胰腺癌。主要的零假设是胰腺癌，因为它发生在家族中，与假定的更常见的散发性类型没有明显的特征。另一种假设是，当充分记录和总体分析时，通过仅在两个亲属中发生胰腺癌确定的一大群核心家庭将显示出与已知的散发性（非家族性）胰腺癌不同的一些独特的人口统计学或实验室特征；此外，即使是与肿瘤标志物生物学、细胞遗传学、分子肿瘤学等跨学科合作者的试点工作，也将产生具体的可测试假设，这些假设可以在后续研究中得到解决。具体目标1 -更新外分泌胰腺腺癌的家族聚集，其中32例由国家癌症研究所和匹兹堡大学的首席研究员确定，并扩大俄克拉何马大学的国家胰腺癌家族登记处，并在持续的基础上积累额外的家族，总数达到150个。具体目标2 -在已登记的家族中，获取相关的病因学信息和生物标本（新鲜、冷冻和固定的恶性和正常组织、淋巴细胞、DNA和血清），并维持标本库。具体目标3 -对登记材料进行初步分析，包括来自患者和一级亲属（可能患有外分泌胰腺癌的高风险人群）的标本。简而言之，我们将继续并扩大胰腺癌跨学科研究的国家研究资源，并促进初步的转化研究。与更大的NCI的乳腺癌和结直肠癌研究合作家庭登记处类似，家族胰腺癌登记处将同等地确定胰腺癌风险增加的人群，这可能对早期检测、预防和创新治疗的研究有用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objective, of which this proposed work is a beginning, is to identify the ecogenetic (gene-environment) origins of a devastating, frequent malignant neoplasm, namely adenocarcinoma of the exocrine pancreas. The plan of attack hinges on the proven strategy of interdisciplinary studies of families that appear to have an excess of cancer, in this case, cancer of the pancreas. The major null hypothesis is that pancreatic cancer, as it occurs in families, has no distinguishing features from the presumedly more frequent sporadic type. The alternative hypothesis is that, when well-documented and analyzed in the aggregate, a large group of nuclear families ascertained through the occurence of pancreatic cancer in just two relatives will show some distinctive demographic or laboratory feature from what is known about sporadic (non-familial) pancreatic cancer; and, further, that even pilot work with interdisciplinary collaborators in tumor marker biology, cytogenetics, molecular oncology, etc., will yield specific testable hypotheses that can be addressed in follow-up investigations. Specific Aim 1 - To update familial aggregations of adenocarcinoma of the exocrine pancreas, 32 of which were identified by the principal investigator at the National Cancer Institute and at the University of Pittsburgh, and to expand at the University of Oklahoma, a national registry of pancreatic cancer families, and to accrue additional families on an ongoing basis to a total of 150. Specific Aim 2 - On registered families, to acquire relevant etiologic information and biological specimens (fresh, frozen, and fixed malignant and normal tissue, lymphocytes, DNA, and sera) and to maintain a specium repository. Specific Aim 3 - To conduct preliminary assays on the registry material, including specimens from patients and from first-degree relatives (who are possibly at high risk of cancer of the exocrine pancreas). In short, we will continue and expand a national research resource of interdisciplinary studies of pancreatic cancer and to catalyze preliminary translational research. Akin to the much larger, NCI's Cooperative Family Registries for Breast and Colorectal Cancer Studies, the Familial Pancreatic Cancer Registry would, pari passu, identify a population at increased risk for pancreatic cancer that may be useful for studies of early detection, prevention, and innovative therapies.