GENE-ENVIRONMENT INTERACTION IN PROSTATE CANCER

前列腺癌中的基因-环境相互作用

• 批准号: 6546675
• 负责人: Benjamin A. Rybicki
• 金额: $ 34.75万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6546675
• 关键词: GENE; ENVIRONMENT; INTERACTION; PROSTATE; CANCER

DESCRIPTION (provided by applicant): Many polycyclic aromatic hydrocarbons (PAH) have carcinogenic potential through the formation of DNA adducts. Differences in PAH-DNA adduct levels between cancer cases and controls and between normal and tumor tissue has been demonstrated in breast and lung cancer. PAH exposures have been found associated with prostate cancer in epidemiologic studies, and DNA adducts have been detected in prostate tissue, but heretofore no effort has been made to link retrospective PAH exposures with the biomarker of PAH-DNA adducts in the prostate. We propose to retrospectively assess the main environmental sources of PAH exposures (e.g., diet, occupation, smoking) and potentially important intervening genetic factors in DNA adduct formation in 400 prostate cancer cases. These genetic factors include polymorphisms in xenobiotic metabolizing enzymes responsible for PAH activation and detoxification and DNA repair genes that can reverse PAH-DNA adduct formation. The proposed study will examine the importance of duration timing and type of PAH exposure, and test the effects of genetic and pathologic factors, in the formation DNA adducts in the prostate. Our proposed study design parallels work currently being done in breast cancer by study investigators, and these combined efforts are geared to offer a promising new line of investigation into the environmental etiology of hormonally-related cancers. The proposed study is a supplemental application to the NIEHS-flinded study, "Gene-Environment Interaction in Prostate Cancer" (5 ROl ES 011126-02) and will utilize the study population that is be enrolled in this study. Our results will provide researchers with a framework to conduct multi-level (e.g., environmental, genetic, biologic) risk assessment in prostate and related cancers where PAH are thought to play a major role in the carcinogenesis pathway.

描述（由申请方提供）：许多多环芳烃（PAH）通过形成DNA加合物具有致癌潜力。在乳腺癌和肺癌中，已经证明了癌症病例和对照之间以及正常组织和肿瘤组织之间PAH-DNA加合物水平的差异。在流行病学研究中发现PAH暴露与前列腺癌相关，并且在前列腺组织中检测到DNA加合物，但迄今为止尚未尝试将回顾性PAH暴露与前列腺中PAH-DNA加合物的生物标志物联系起来。我们建议回顾性评估PAH暴露的主要环境来源（例如，饮食，职业，吸烟）和潜在的重要干预遗传因素的DNA加合物的形成在400例前列腺癌病例。这些遗传因素包括负责PAH激活和解毒的异生素代谢酶的多态性以及可以逆转PAH-DNA加合物形成的DNA修复基因。拟议的研究将检查PAH暴露的持续时间和类型的重要性，并测试遗传和病理因素在前列腺DNA加合物形成中的影响。我们提出的研究设计与研究人员目前在乳腺癌中所做的工作相似，这些共同努力旨在为乳腺癌相关癌症的环境病因学提供一条有前途的新的调查路线。该拟定研究是对NIEHS支持的研究“前列腺癌中的基因-环境相互作用”（5 RO 1 ES 011126-02）的补充申请，并将利用本研究中招募的研究人群。我们的研究结果将为研究人员提供一个框架，进行多层次（例如，环境、遗传、生物）风险评估，其中PAH被认为在致癌途径中起主要作用。