GENE-ENVIRONMENT INTERACTION IN PROSTATE CANCER

前列腺癌中的基因-环境相互作用

• 批准号: 6800602
• 负责人: Benjamin A. Rybicki
• 金额: $ 7.19万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6800602
• 关键词: cancer risk; chemical related neoplasm /cancer; clinical research; environment related neoplasm /cancer; gene environment interaction; gene interaction; genetic susceptibility; human subject; lifestyle; neoplasm /cancer epidemiology; neoplasm /cancer genetics; occupational hazard; prostate neoplasms; racial /ethnic difference; radiation related neoplasm /cancer

DESCRIPTION (Adapted from applicant's abstract): Prostate carcinogenesis likely involves a complex interplay between inherited genetic susceptibility and exogenous and endogenous exposures. Based on our current understanding of prostate carcinogenesis, we propose a hybrid case-only/case-control study designed to measure the joint effects of putative genetic and environmental risk factors. We plan to enroll 440 incident prostate cancer cases under age 70 and 220 race and age frequency-matched healthy controls. This study will be carried out in a population evenly divided between Caucasians and African-Americans, so that race-specific risk factors and interactions can be identified. The main goals of our study are: 1) to determine whether selected occupational (i.e., cadmium, zinc and polycyclic hydrocarbons), environmental (i.e., diet, ultraviolet radiation), lifestyle (i.e., physical activity) and genetic (i.e., CYP17, CYP3A4, GSTP1, SRD5A2, vitamin D receptor, androgen receptor, metallothionein 2A, HSD3B2polyhmorphisms) risk factors are associated with increased risk for prostate cancer; and 2) to test combinations of the above genetic and environmental risk factors for putative gene-environment and gene-gene interactions based on their posited role in prostate carcinogenesis. The inclusion of controls in our study design will allow us to estimate main effects and test whether genetic and environmental risk factors are independent. If the latter is true, then we can use our larger case sample to test for specific gene-environment interactions based on biologically plausible scenarios. The analysis will be conducted using log-linear models, which uniquely allow us to include or exclude control data depending upon our specific analytic goals (e.g., estimation of main effects vs. interaction terms). This study will be the first known effort specifically designed to test for gene-environmental interaction in prostate carcinogenesis.

描述（改编自申请人的摘要）：前列腺致癌 涉及遗传遗传敏感性和 外源和内源性暴露。基于我们目前对 前列腺致癌作用，我们提出了一项仅杂化病例/病例对照研究 旨在测量推定遗传和环境的关节作用 风险因素。我们计划招募440个事件的前列腺癌病例70岁以下 和220种比赛和年龄频率匹配的健康对照。这项研究将是 在高加索人和 非洲裔美国人，因此，特定种族的风险因素和互动可以是 确定。我们研究的主要目标是：1）确定是否选择 职业（即镉，锌和多环芳烃），环境 （即饮食，紫外线辐射），生活方式（即体育锻炼）和 遗传（即CYP17，CYP3A4，GSTP1，SRD5A2，维生素D受体，雄激素 受体，金属硫蛋白2a，HSD3B2多态）风险因素是相关的 患有前列腺癌的风险增加； 2）测试组合 推定基因环境的遗传和环境风险因素高于 基因 - 基因相互作用基于其在前列腺癌发生中的作用。 在我们的研究设计中包含控件将使我们能够估计主要 影响并测试遗传和环境风险因素是否是 独立的。如果后者是真的，那么我们可以使用较大的案例样本 基于生物学上合理的特定基因环境相互作用的特定基因环境相互作用 方案。分析将使用对数线性模型进行，该模型 独特允许我们根据我们的来包括或排除控制数据 特定的分析目标（例如，主要影响与互动的估计 术语）。这项研究将是专门针对测试的首次已知工作 用于前列腺癌发生中的基因环境相互作用。