Endotoxin and Lung Cancer: Separating Healthy Worker Bias From Biologic Mechanism

内毒素和肺癌：将健康工人的偏见与生物机制分开

• 批准号: 7895747
• 负责人: Katie M. Applebaum
• 金额: $ 10.8万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895747
• 关键词: Endotoxin; Lung; Cancer; Separating; Healthy

DESCRIPTION (provided by applicant): The candidate's education and research have focused on environmental and occupational epidemiology, with particular interest in gene-environment interactions and modeling biologic pathways. The candidate's research in an occupational cohort study led her to observe that, studies that include workers hired prior to the start of follow-up over-sample healthier workers, which exaggerates the healthy worker survivor effect (HWSE) and induces a downward bias. This proposed training will allow her to gain skills to develop epidemiologic methods to address this and other occupational methods issues as well as enhance her potential to develop into an independent investigator focused on occupational research. Mentors and coinvestigators for this proposal have expertise in epidemiologic and quantitative methods, occupational epidemiology, and modeling occupational exposures. The training involves gaining experience in causal modeling, designing biologic models that account for an immunologic response to exposure, and developing and testing novel methods to minimize HWSE bias. The training will also provide opportunities for her to begin to establish an independent research program. The study population for the proposed work is the Shanghai female textile workers study, a case-cohort study of 3184 controls and 628 cases of lung cancer. Previously, an inverse association between lung cancer and endotoxin was reported. This is biologically plausible given that endotoxin may lead to immunomodulation, which itself may be anticarcinogenic. However, the study population includes only subjects hired prior to the start of follow-up, which may partially explain this inverse association. The specific aims are: 1) to estimate the exposure-response for endotoxin and lung cancer accounting for immune response modifiers (e.g., cessation of exposure and hormonal changes); 2) to determine how much bias is introduced from the inclusion of subjects hired much earlier than the start of follow-up; and 3) to develop and compare methods for controlling for this form of HWSE bias. This research directly addresses a common problem in occupational health research - how to handle the exaggerated HWSE bias when subjects were hired prior to the start of follow-up. In addition, advanced training in developing epidemiologic methods and modeling biologic mechanisms will allow the candidate to develop into an independent investigator.

描述（由申请人提供）：候选人的教育和研究集中在环境和职业流行病学，对基因-环境相互作用和模拟生物途径特别感兴趣。这位候选人在一项职业队列研究中的研究使她观察到，包括在开始随访之前雇用的工人的研究对健康工人进行了过度抽样，这夸大了健康工人幸存者效应（HWSE）并引起了向下的偏见。这项拟议的培训将使她获得开发流行病学方法的技能，以解决这一问题和其他职业方法问题，并提高她发展成为一名专注于职业研究的独立调查员的潜力。本提案的导师和共同研究者具有流行病学和定量方法、职业流行病学和职业暴露建模方面的专业知识。培训包括获得因果建模的经验，设计生物模型，解释对暴露的免疫反应，以及开发和测试新方法以最大限度地减少HWSE偏倚。培训还将为她开始建立独立的研究计划提供机会。拟开展的研究人群是上海纺织女工研究，这是一项包括3184名对照组和628名肺癌患者的病例队列研究。 以前，肺癌和内毒素之间的负相关性被报道。这在生物学上是合理的，因为内毒素可能导致免疫调节，而免疫调节本身可能是抗癌的。然而，研究人群仅包括随访开始前雇用的受试者，这可能部分解释了这种负相关。具体目的是：1）估计内毒素和肺癌的免疫应答，考虑免疫应答调节剂（例如，停止暴露和激素变化）; 2）确定纳入比随访开始早得多的受试者引入了多少偏倚; 3）开发和比较控制这种形式的HWSE偏倚的方法。这项研究直接解决了职业健康研究中的一个常见问题-如何处理被夸大的HWSE偏见时，受试者被雇用之前开始随访。此外，在开发流行病学方法和建模生物机制方面的高级培训将使候选人能够发展成为独立的研究者。