Occupational Safety and Health Research (R01)

 描述(由申请人提供)：我们建议继续我们对密歇根州汽车工人队列中金属加工液(MWF)健康影响的研究，重点关注癌症发病率，并应用必要的先进统计方法来表征暴露-反应关系，而不会因健康工人幸存者效应(HWSE)而产生偏见。尽管我们已经报告了强有力的证据表明，直接接触MWF会增加患膀胱癌和黑色素瘤皮肤癌的风险，但预期与呼吸系统、消化系统和其他癌症的联系还不太清楚。我们现在有了大量的经验，在这个队列的死亡率研究中应用因果g方法来控制HWSE-从第一次在职业研究中实施g估计，到我们最近将定量暴露纳入这一方法。与对HWSE的普遍看法不同，我们之前的工作表明，这种偏见会影响癌症和其他慢性病的研究。虽然最初的UAW-GM队列的死亡率跟踪始于1941年，但癌症发病率直到几十年后才能观察到，当时启动了两个癌症登记--1973年底特律SEER登记和1985年密歇根癌症登记。因此，有资格参加这项拟议癌症研究的37,786名工人的子队列只包括那些存活到较晚开始随访的人，因此如果如我们所示，接触MWF会增加死亡风险，那么癌症发病率队列可能会包括更少容易受到MWF接触的健康影响的受试者。在这项关于长期接触MWF与选定癌症风险的研究中，我们建议应用一种基于逆加权的新方法来解决左截断问题，作为健康工人幸存者偏见的另一个来源。MWF是油和化学添加剂的复杂混合物，广泛用于冷却和润滑金属加工操作。喷洒MWF时产生的空气颗粒物(PM)与交通相关的PM具有共同的成分，与肺癌有关，但比环境水平高出两个数量级。因此，MWF对数百万汽车制造、特殊金属和其他与电子制造、新技术或替代能源相关的金属加工工作的工人构成了潜在的危险。2010年，全美汽车工人联合会再次向OSHA请愿，主要根据哮喘和过敏性肺炎制定MWF标准，但未获成功。我们提议的研究的目标是澄清癌症风险--从病因学和风险评估的角度--可能是必要的刺激预防活动。

 DESCRIPTION (provided by applicant): We propose to continue our study of the health effects of metalworking fluids (MWF) in a cohort of Michigan autoworkers by focusing on cancer incidence and applying the advanced statistical methods necessary to characterize exposure-response relations without bias due to the healthy worker survivor effect (HWSE). Though we have reported strong evidence that straight MWF exposure increases the risk of bladder cancer and melanoma skin cancer, anticipated links with respiratory, digestive and other cancers have been less clear. We now have substantial experience applying causal g-methods to control for HWSE in mortality studies of this cohort - from the first implementation of g-estimation in an occupational study, to our recent incorporation of quantitative exposure into this approach. In contrast with common perceptions about HWSE, our previous work suggests that the bias can affect studies of cancer as well as other chronic diseases. Whereas mortality follow-up began in 1941 for the original UAW-GM cohort, cancer incidence cannot be observed until decades later when two cancer registries were initiated - the Detroit SEER registry in 1973 and Michigan Cancer registry in 1985. Thus the sub-cohort of 37,786 workers eligible for this proposed cancer study includes only those who survived until the later start of follow-up, and so is left truncated If, as we have shown, MWF exposure increases mortality risk, then the cancer incidence cohort will likely include fewer subjects susceptible to the health effects of MWF exposure. We propose to apply a novel approach based on inverse weighting to address left truncation, as an additional source of healthy worker survivor bias, in this proposed study of long-term exposure to MWF in relation to risk of selected cancers. MWF are complex mixtures of oils and chemical additives widely used to cool and lubricate metal machining operations. The airborne particulate matter (PM) generated when MWF are sprayed, shares common components with traffic related PM that have been linked to lung cancer, but occurs at up to two orders of magnitude higher than ambient levels. Thus MWF pose a potential hazard to millions of workers in automobile manufacturing, specialty metals and other metal machining jobs related to electronics manufacturing, new technologies, or alternative energy. In 2010, the United Autoworkers again unsuccessfully petitioned OSHA for a MWF standard primarily on the basis of asthma and hypersensitivity pneumonitis. The goal of our proposed study, to clarify the cancer risk - both in terms of etiology and risk assessment - may be necessary spur prevention activities.