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（由申请人提供）：许多多环芳烃（PAH）通过形成DNA加合物具有致癌潜力。癌症和对照组之间以及正常组织和肿瘤组织之间的PAH-DNA加合物水平的差异已在乳腺癌和肺癌中证明。在流行病学研究中发现了与前列腺癌相关的PAH暴露，并且在前列腺组织中发现了DNA加合物，但迄今为止，迄今无需努力将回顾性的PAH暴露与前列腺中的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），以及在400个前列腺癌病例中DNA加合物形成中潜在的重要中间遗传因素。这些遗传因素包括负责PAH激活和排毒的异生物代谢酶的多态性，以及可以逆转PAH-DNA加合物形成的DNA修复基因。拟议的研究将检查持续时间和PAH暴露类型的重要性，并测试遗传和病理因素的影响，在前列腺中的形成DNA加合物中。我们提出的研究设计与研究研究人员目前在乳腺癌中进行的工作相似之处，这些合并的努力旨在为荷尔蒙相关癌症的环境病因提供有希望的新研究。拟议的研究是对NIEHS倾斜的研究的补充应用，“前列腺癌中的基因 - 环境相互作用”（5 ROL ES 011126-02），并将利用本研究的研究人群。我们的结果将为研究人员提供一个框架，以在前列腺和相关癌症中进行多层次（例如环境，遗传，生物学）风险评估，其中PAH被认为在致癌途径中起主要作用。