Prostate Cancer Risk and Outcome in WTC respondents

世贸中心受访者的前列腺癌风险和结果

• 批准号: 8695439
• 负责人: EMANUELA TAIOLI
• 金额: $ 45.07万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695439
• 关键词: Prostate; Cancer; Risk; Outcome; WTC

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.

描述（由申请人提供）：纽约西奈山世贸中心 (WTC) 健康计划 (WTCHP) 中的救援和恢复人员中前列腺癌发病率过高。据报道，在一个单独的计划中，暴露于世贸中心的消防员也出现了过量的情况。目前尚不清楚这一超量是否与世贸中心相关的暴露有关，或者是否是人为造成的。目前对前列腺癌（美国男性中最常见的癌症）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于 WTCHP 及其他领域具有重要意义。相反，发现 WTCHP 参与者的过度风险并非归因于 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] 筛查而导致过度诊断），这对 WTCHP 成员来说是一个重要信息。该项目的目标是阐明 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。该项目将通过研究前列腺癌风险增加的其他原因，补充根据已计划的世贸中心相关暴露对癌症风险进行的分析，并将调查 WTCHP 参与者中诊断出的前列腺癌从临床和分子角度来看是否与世贸中心无关患者中诊断出的前列腺癌不同。 具体来说，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）；将比较两组患者的肿瘤大小、淋巴结受累、局部和远处转移扩散、诊断时的 PSA 以及既往 PSA 检测史。 将通过 WTCHP 患者和匹配的非 WTC 前列腺癌的前列腺癌样本中的免疫组织化学和炎症分子标记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，将比较 WTCHP 前列腺癌患者组织和与 WTC 无关的匹配前列腺癌组织中 DNA 甲基化作为肿瘤侵袭性的标志。 研究结果将对前列腺癌（WTCHP 男性成员中最常见的癌症）的监测和临床管理产生实际影响。该项目将生成有关前列腺癌侵袭性生物标志物的新数据，可用于做出临床治疗决策。

项目成果

Prostate cancer characteristics in the World Trade Center cohort, 2002-2013.

• DOI: 10.1097/cej.0000000000000315
• 发表时间: 2018-07
• 期刊: European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
• 作者: Hashim D;Boffetta P;Galsky M;Oh W;Lucchini R;Crane M;Luft B;Moline J;Udasin I;Harrison D;Taioli E
• 通讯作者: Taioli E