ECOGENETICS OF PANCREATIC CANCER: A NATIONAL REGISTRY OF FAMILIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项拟议的工作是一个开始，其长期目标是确定一种毁灭性的、频繁的恶性肿瘤，即外分泌腺癌的生态(基因-环境)起源。攻击计划取决于对似乎有过多癌症的家庭进行跨学科研究的成熟策略，在这种情况下，癌症是胰腺癌。主要的无效假设是胰腺癌，因为它发生在家族中，没有区别于推测更常见的散发性类型的特征。另一种假设是，当很好地记录和分析时，通过仅在两个亲属中发生胰腺癌而确定的一大群核心家族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学或实验室特征；此外，即使是与肿瘤标记物生物学、细胞遗传学、分子肿瘤学等跨学科合作者的试点工作，也将产生具体的可检验的假说，可以在后续研究中解决。具体目标1-更新胰腺外分泌腺癌的家族聚集性，其中32个是由国家癌症研究所和匹兹堡大学的首席研究员确定的，并在俄克拉荷马大学扩大，这是一个全国性的胰腺癌家族登记机构，并在持续的基础上增加新的家庭，总数达到150个。具体目标2-关于登记的家庭，获得相关的病因学信息和生物标本(新鲜的、冷冻的和固定的恶性和正常组织、淋巴细胞、DNA和血清)，并维持一个专门的储存库。具体目标3--对登记材料进行初步分析，包括病人和一级亲属(他们可能有患胰腺外分泌癌的高风险)的标本。简而言之，我们将继续并扩大胰腺癌跨学科研究的全国性研究资源，并催化初步的翻译研究。与规模更大的NCI乳腺癌和结直肠癌研究合作家庭登记处类似，家族性胰腺癌登记处将识别出胰腺癌风险较高的人群，这可能有助于早期发现、预防和创新治疗的研究。

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.