GENETICS EPIDEMIOLOGY OF PANCREATIC CANCERS

胰腺癌的遗传学流行病学

• 批准号: 2109989
• 负责人: Christopher E. ASTON
• 金额: $ 3.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2109989
• 关键词: age difference; alcoholism /alcohol abuse; cancer registry /resource; cancer risk; computer data analysis; dietary lipid; family genetics; fruit; gender difference; human data; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition aspect of cancer; nutrition related neoplasm /cancer; pancreas neoplasms; racial /ethnic difference; tobacco abuse; vegetables; age difference; alcoholism /alcohol abuse; cancer registry /resource; cancer risk; computer data analysis; dietary lipid; family genetics; fruit; gender difference; human data; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition aspect of cancer; nutrition related neoplasm /cancer; pancreas neoplasms; racial /ethnic difference; tobacco abuse; vegetables

Cancer of the pancreas, mostly adenocarcinoma of the exocrine pancreas, is one of the most rapidly fatal of the cancers. This cancer is the fifth leading cause of all cancer deaths, totaling an estimated 27,700 new cases and 25,000 deaths in 1992. No safe and effective early screening methods are available. Several environmental determinants and molecular genetic pathogenetic mechanisms, as well as familial inheritance have been suggested. However, no clear, single, unifying etiologic hypothesis has been established. The study proposed will elucidate the etiology of adenocarcinoma of the exocrine pancreas ("pancreatic cancer") through a rigorous application of established epidemiologic methods to data on approximately 100 families ascertained through individuals diagnosed with pancreatic cancer. The families are part of the American Cancer Society funded initiative "The Ecogenetics of Pancreatic Cancer: A National Registry of Families." We will use three approaches to investigate the genetic epidemiology of pancreatic cancer. First, we will apply logistic regression models to examine the effects of observable covariates on risk for pancreatic cancer. To account for the natural correlation of the observations within families, quasi-likelihood methods will be used to incorporate an overall correlation in risk among family members; an approach usually termed Generalized Estimating Equations or GEE1. Second, we will assess the risk in these families to various phenotypic traits, such as pancreatic cancer or cancers generally, which is in excess of that expected for a similar group of individuals drawn at random from the general population; a test of familial aggregation. Third, we will use complex segregation analyses to identify patterns of inheritance of pancreatic cancer in these families. We will also examine the evidence for genetic heterogeneity. As part of this third analytic method, we will use computer simulations to establish an appropriate correction for the method in which these families were ascertained. The results of this analysis will be used in the complex segregation analyses. In brief, this is an application to the Small Grants Program for Epidemiology for funding to analyze existing data and to resolve a methodological problem.

胰腺癌，主要是外分泌胰腺的腺癌，是 癌症中最迅速致命的是。这个癌症是第五个 所有癌症死亡的主要原因，估计有27,700例新病例 1992年25,000人死亡。没有安全有效的早期筛查方法 可用。几种环境决定因素和分子遗传 致病机制以及家族遗传已经 建议。但是，没有明确的，单一的，统一的病因学假设有 已建立。提出的研究将阐明 外分泌胰腺（“胰腺癌”）的腺癌通过 严格将已建立的流行病学方法应用于数据 大约有100个家庭通过诊断的人确定 胰腺癌。这些家庭是美国癌症协会的一部分 资助的倡议“胰腺癌的生态学：国家 家庭注册表。“我们将使用三种方法调查 胰腺癌的遗传流行病学。首先，我们将应用物流 回归模型以检查可观察到的协变量对风险的影响 用于胰腺癌。考虑到自然相关性 家庭中的观察，准类方法将用于 将家庭成员的风险总体相关性纳入；一个 方法通常称为广义估计方程或GEE1。第二， 我们将评估这些家庭的风险，以表型特征， 例如胰腺癌或癌症通常 对于一组类似的个体的期望，从 一般人群；家族聚集的测试。第三，我们将使用 复杂的分离分析以识别继承模式 这些家庭的胰腺癌。我们还将检查证据 遗传异质性。作为第三种分析方法的一部分，我们将使用 计算机模拟以建立适当的校正该方法 这些家庭被确定。该分析的结果 将用于复杂的分离分析。 简而言之，这是针对小型赠款计划的申请 资金流行病学以分析现有数据并解决 方法论问题。