ECOGENETICS OF PANCREATIC CANCER: A NATIONAL REGISTRY OF FAMILIES

点击翻译按钮获取中文摘要

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.