RISK ESTIMATION AND MODIFIER GENES IN INHERITED CANCER

遗传性癌症的风险评估和修饰基因

• 批准号: 6522495
• 负责人: David E. Goldgar
• 金额: $ 1.91万
• 依托单位: INTERNATIONAL AGENCY FOR RES ON CANCER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-21 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522495
• 关键词: age difference; brca gene; cancer risk; carcinogenesis; disease /disorder onset; environment related neoplasm /cancer; family genetics; gene environment interaction; gene interaction; genetic carriers; genetic disorder; genetic susceptibility; human data; linkage mapping; neoplasm /cancer genetics

DESCRIPTION (Adapted from investigator's abstract): During the past decade, progress has been made in localizing and identifying specific genes such as BRCA1 and p16 which when altered can confer a markedly increased susceptibility to relatively common cancers. Although variations at these genes apparently increase risk of cancer at a variety of anatomical sites, there is controversy about the magnitude of these risks. Risks derived from population-based studies have produced lower estimates of risk than those estimated from studies of single large families or series of multiple high-risk families. Whether these differences reflect inherent biases in the methods used for risk estimation or represent the effects of modifying loci segregating in high-risk families is not obvious. Statistical methods for estimation of gene effects are relatively underdeveloped. Additionally, there have been no studies that examine the feasibility of mapping hypothesized modifier loci in the context of a total genome search. This project seeks to examine the efficiency and bias associated with various sampling designs and statistical methods for estimation of cancer risks due to such genes. Monte-Carlo simulation and existing datasets encompassing the three approaches described above will be used for the evaluation of a variety of methods. Several designs for a) testing the effect on risk modification of specific candidate loci; b) detecting the presence of residual genetic effects; and c) examining the power of different sampling designs for genome-wide screens to localize modifier loci also will be examined.

描述（根据调查员的摘要改编）：在过去的十年中， 在本地化和识别特定基因（例如 BRCA1和p16，当更改后可以显着提高易感性 相对常见的癌症。尽管这些基因的变化显然是 增加各种解剖部位的癌症风险，存在争议 关于这些风险的大小。源自人群研究的风险 比从研究中估计的估计值较低 单身大家庭或一系列多种高风险家庭。是否这些 差异反映了用于风险估计或 表示在高危家族中修改基因座分离的效果是 并不明显。估计基因效应的统计方法相对 欠发达。此外，没有研究检查 在总计中绘制假设的修饰基因座的可行性 基因组搜索。该项目旨在检查相关的效率和偏见 采用各种抽样设计和统计方法来估计癌症 由于这种基因而引起的风险。蒙特卡洛模拟和现有数据集 涵盖上述三种方法将用于 评估多种方法。 a）测试效果的几种设计 特定候选基因座的风险修改； b）检测存在 残留遗传作用； c）检查不同采样的功能 针对全基因组屏幕的设计，以本地化修饰符基因座的定位也将是 检查。