Occupational Safety and Health Research (R01)

 描述（由申请人提供）：我们建议继续研究金属加工液（MWF）对密歇根州汽车工人队列的健康影响，重点关注癌症发病率，并应用先进的统计方法来表征健康工人幸存者效应（HWSE）造成的无偏倚的生存-反应关系。虽然我们已经报告了强有力的证据表明直接接触MWF会增加膀胱癌和黑色素瘤皮肤癌的风险，但与呼吸道，消化道和其他癌症的预期联系尚不清楚。我们现在有大量的经验，应用因果g-方法来控制HWSE的死亡率研究的这个队列-从第一次实施g-估计在职业研究，我们最近纳入定量暴露到这种方法。与对HWSE的普遍看法相反，我们以前的工作表明，这种偏见可能会影响癌症和其他慢性疾病的研究。虽然最初的UAW-GM队列的死亡率随访始于1941年，但直到几十年后才开始观察癌症发病率，当时启动了两个癌症登记处-1973年的底特律SEER登记处和1985年的密歇根州癌症登记处。因此，有资格参加这项拟议的癌症研究的37，786名工人的子队列仅包括那些存活到随后开始随访的人，因此被截断。如果，正如我们已经表明的那样，MWF暴露增加死亡风险，那么癌症发病率队列可能会包括更少的易受MWF暴露健康影响的受试者。在这项拟议的长期暴露于MWF与选定癌症风险相关的研究中，我们建议应用一种基于逆加权的新型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。喷雾MWF时产生的空气中颗粒物（PM）与交通相关的PM具有共同的成分，这些成分与肺癌有关，但发生的数量级比环境水平高出两个数量级。因此，MWF对数百万从事汽车制造、特种金属和其他与电子制造、新技术或替代能源有关的金属加工工作的工人构成潜在危险。2010年，美国汽车工人联合会（United Autoworkers）再次向OSHA申请MWF标准，主要是基于哮喘和过敏性肺炎，但没有成功。我们提出的研究的目标，以澄清癌症的风险-无论是在病因和风险评估方面-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.