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)包括的世贸中心(WTC)救援和恢复工作人员中，发现前列腺癌发病率过高。据报道，在另一项计划中，接触WTC的消防员也出现了超标。目前尚不清楚超标是与WTC相关的暴露有关，还是代表着一种艺术品。前列腺癌是美国男性最常见的癌症，目前对其病因和发病机制的了解有限，这种癌症与WTC相关暴露之间的联系将对WTCHP和其他疾病具有非常重要的意义。相反，WTCHP参与者的过度风险不是由于WTC相关的暴露，而是其他因素(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)，这一发现将向WTCHP成员传达一个重要信息。该项目的目的是阐明WTCHP参与者前列腺癌发病率增加的原因，并探索这些癌症的行为。该项目将补充已经计划的根据WTC相关暴露对癌症风险的分析，通过寻找前列腺癌风险增加的其他原因，并将调查WTCHP参与者中被诊断为前列腺癌的患者是否从临床和分子角度与WTC无关患者的前列腺癌不同。具体地说，该项目将调查WTC应答者和匹配的非WTC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)；肿瘤大小、结节受累、局部和远处转移扩散、确诊时的PSA以及以前的PSA检测病史将在两组患者中进行比较。将通过免疫组织化学和炎症分子标志物研究WTCHP患者和匹配的非WTC前列腺癌患者前列腺癌样本中肿瘤的分子特征，以确定WTCHP患者的肿瘤是否发生在不同的“炎症”微环境中。最后，在WTCHP前列腺癌患者和与WTC无关的匹配前列腺癌患者的组织中，DNA甲基化作为肿瘤侵袭性的标志将进行比较。这一结果将对前列腺癌的监测和临床治疗具有实际意义。前列腺癌是WTCHP男性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记物的新数据，这些数据可用于临床治疗决策。

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.