METALWORKING FLUIDS AND AERODIGESTIVE CANCER RISK

金属加工液和呼吸消化道癌症风险

• 批准号: 2842894
• 负责人: DAVID KRIEBEL
• 金额: $ 13.86万
• 依托单位: UNIVERSITY OF MASSACHUSETTS LOWELL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842894
• 关键词: alcoholism /alcohol abuse; cancer risk; carcinoma; clinical research; esophagus neoplasm; fluid; human data; larynx neoplasms; metals; neoplasm /cancer epidemiology; occupational hazard; occupational health /safety; tobacco abuse

Millions of workers are routinely exposed to metal- working fluids (MWF) when these complex chemical mixtures are sprayed on metal as it is machined. Growing evidence suggests that there are carcinogenic effects of at least some types of MWF. In particular, the largest study of exposed workers yet conducted (a study of 46,000 United Automobile Workers/General Motors employees) has found strongly increased risks of laryngeal and esophageal carcinomas. The goal of the proposed work is to substantially expand the epidemiologic evidence linking MWF to cancers of the upper aerodigestive tract by a series of statistical studies using the UAW/GM data set. These analyses are designed to clarify several important outstanding issues which currently limit conclusions on the risk from these widespread industrial chemicals. This project will: 1. Estimate cancer risks from exposure to MWF for the upper aerodigestive tract, not by traditional organ designations (larynx and esophagus, for example), but by groupings which correspond more closely to routes of exposure and likely target tissues for exogenous chemicals: epilarynx and hypopharynx (both inhalation and ingestion); endolarynx (exposure by inhalation); and esophagus excluding adenocarcinoma of the esophagogastric junction (primarily ingestion); 2. Evaluate the magnitude of potential confounding by tobacco and alcohol in this cohort (which lacks individual data on these risk factors) by using the method of indirect adjustment; and 3. Apply the Moolgavkar-Knudson two-stage cancer model to the quantitative MWF exposure data to provide a biologically-based method to investigate the temporal (early versus late stage) contribution of different types and components of MWF to cancer risks in the upper aerodigestive tract. In addition to addressing the specific issue of metalworking fluids and cancer, this project will also contribute more generally to environmental cancer epidemiology by demonstrating the feasibility of incorporating more sophisticated, biologically-based, modeling methods into the widely used retrospective cohort study.

数以百万计的工人在金属加工过程中经常接触到金属加工液（MWF），这些复杂的化学混合物被喷在金属上。越来越多的证据表明，至少某些类型的MWF具有致癌作用。尤其值得一提的是，迄今为止对暴露的工人进行的最大规模的研究（一项对46,000名美国汽车工人联合会/通用汽车公司员工的研究）发现，喉癌和食管癌的风险大大增加。本研究的目标是通过一系列使用UAW/GM数据集的统计研究，实质性地扩大MWF与上气消化道癌症之间的流行病学证据。这些分析的目的是澄清几个重要的突出问题，这些问题目前限制了对这些广泛使用的工业化学品的危险作出结论。本项目将：1；评估上呼吸道接触MWF的癌症风险，不是通过传统的器官指定（例如喉部和食道），而是通过与接触途径和外源性化学物质可能的靶组织更接近的分组：鼻咽和下咽（吸入和摄入）；喉内（吸入暴露）；以及食管，不包括食管胃交界处的腺癌（主要是食入）；2. 使用间接调整方法评估该队列中烟草和酒精潜在混淆的程度（缺乏这些风险因素的个人数据）；和3。将Moolgavkar-Knudson两期癌症模型应用于MWF的定量暴露数据，提供一种基于生物学的方法来研究不同类型和成分的MWF对上气消化道癌症风险的时间（早期和晚期）贡献。除了解决金属加工液和癌症的具体问题外，该项目还将通过展示将更复杂的、基于生物学的建模方法纳入广泛使用的回顾性队列研究的可行性，为环境癌症流行病学做出更广泛的贡献。