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）：在纽约西奈山世界贸易中心（WTC）卫生计划（WTCHP）中，在世界贸易中心（WTC）救援和恢复工作人员中发现了前列腺癌的过度发病率。据报道，在一个单独的项目中，暴露于WTC的消防队员也有过量的情况。目前尚不清楚过量是否与WTC相关的暴露或代表一个伪影。目前对前列腺癌（美国男性中最常见的癌症）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于WTCHP及其他方面具有重要意义。相反，WTCHP参与者的过度风险并不归因于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]筛查而导致过度诊断）将向WTCHP成员发出重要信息。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，补充已经计划的WTC相关暴露的癌症风险分析，并将调查WTCHP参与者中诊断的前列腺癌是否与WTC无关患者的前列腺癌有临床和分子观点的不同。 具体而言，该项目将研究WTC应答者和匹配的非WTC前列腺癌中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，淋巴结受累，局部和远处转移扩散，诊断时的PSA以及PSA检测的既往史将在两组患者之间进行比较。 肿瘤的分子特征将通过来自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志物来研究，以确定WTCHP患者中的肿瘤是否出现在不同的“炎症”微环境中。 最后，将比较WTCHP前列腺癌患者和与WTC无关的匹配前列腺癌组织中作为肿瘤侵袭性标志物的DNA甲基化。 研究结果将对前列腺癌的监测和临床管理产生实际影响，前列腺癌是WTCHP男性成员中最常见的癌症。该项目将产生关于前列腺癌侵袭性生物标志物的新数据，可用于临床治疗决策。

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