Prostate Cancer Risk and Outcome in WTC respondents

描述（由申请人提供）：在纽约西奈山世贸中心健康计划（WTCHP）的世贸中心（WTC）救援和恢复工作人员中，前列腺癌的发病率过高。据报道，在另一个项目中，接触世贸中心的消防员也出现了过量。目前尚不清楚过量是与wtc相关的暴露有关，还是人为的。前列腺癌是美国男性中最常见的癌症，目前对前列腺癌的病因和发病机制的了解有限，这种癌症与wtc相关暴露之间的关联对WTCHP及其他方面具有重要意义。相反，发现WTCHP参与者的过度风险不归因于WTC相关暴露，而是归因于其他因素（例如，由于加强监测和前列腺特异性抗原[PSA]筛查而过度诊断），这将向WTCHP成员传达一个重要信息。该项目的目的是阐明WTCHP参与者中前列腺癌发病率增加的原因，并探讨这些癌症的行为。该项目将通过研究前列腺癌风险增加的其他原因，对已经计划的wtc相关暴露的癌症风险分析进行补充，并从临床和分子角度调查WTCHP参与者中诊断出的前列腺癌是否与wtc无关患者的前列腺癌不同。具体而言，该项目将调查WTC应答者和匹配的非WTC前列腺癌患者前列腺癌的临床和流行病学特征：D'Amico风险评分（包括Gleason评分和肿瘤分期）；比较两组患者的肿瘤大小、淋巴结累及、局部和远处转移性扩散、诊断时的PSA以及既往PSA检测史。通过免疫组织化学和WTCHP患者和匹配的非wtc前列腺癌前列腺癌样本中的炎症分子标志物来研究肿瘤的分子特征，以确定WTCHP患者的肿瘤是否出现在不同的“炎症”微环境中。最后，我们将比较DNA甲基化作为WTCHP前列腺癌患者和与WTC无关的匹配前列腺癌组织中肿瘤侵袭性的标志物。该结果将对前列腺癌的监测和临床管理具有实际意义，前列腺癌是男性WTCHP成员中最常见的癌症。该项目将产生前列腺癌侵袭性生物标志物的新数据，可用于制定临床治疗决策。

DESCRIPTION (provided by applicant): An excess incidence of prostate cancer has been identified among World Trade Center (WTC) rescue and recovery workers included in the WTC Health Program (WTCHP) at Mount Sinai in New York. An excess has also been reported among WTC-exposed firefighters included in a separate program. It is unclear whether the excess is associated with WTC-related exposures or represents an artifact. Current understanding of the etiology and pathogenesis of prostate cancer - the most common cancer in US men - is limited, and an association between this cancer and WTC-related exposures would bear great importance for the WTCHP and beyond. Conversely, the finding that excess risk among WTCHP participants is not attributable to WTC related exposures, but to other factors (e.g., over-diagnosis because of enhanced surveillance and screening with prostate specific antigen [PSA]) would represent an important message to WTCHP members. The objectives of this project are to elucidate the reasons for the increased incidence of prostate cancer among WTCHP participants and to explore the behavior of these cancers. The project will complement an analysis of cancer risk according to WTC-related exposures that is already planned, by looking at other reasons for an increased prostate cancer risk and will investigate whether prostate cancers diagnosed among WTCHP participants differ from a clinical and molecular viewpoint from prostate cancers in WTC-unrelated patients. Specifically, the project will investigate clinical and epidemiological characteristics of prostate cancer in WTC responders and matched non-WTC prostate cancers: D'Amico risk score (comprising Gleason score and tumor stage); tumor size, nodal involvement, local and distant metastatic spread, PSA at diagnosis, as well as previous history of PSA testing will be compared between the two groups of patients. Molecular characteristics of the tumors will be studied through immunohistochemistry and molecular markers of inflammation in prostate cancer samples from WTCHP patients and matched non-WTC prostate cancers, to determine if tumors in WTCHP patients arise in a different "inflammatory" microenvironment. Finally, DNA methylation as a marker of tumor aggressiveness in tissue from WTCHP prostate cancer patients and in matched prostate cancers not related to WTC will be compared. The results will have practical implications on the surveillance and clinical management of prostate cancer, the most common cancer among male WTCHP members. The project will generate novel data on biomarkers of prostate cancer aggressiveness that could be used to make decisions on clinical treatment.