In this revised proposal we highlight cancers among female autoworkers (breast, ovary, cervix, lung and colorectal), in addition to selected cancers among males in our continued study of metalworking fluids (MWF) exposure in a cohort of UAW-GM autoworkers. The proposed in-depth, exposure-response analyses of cancer incidence for male and female autoworkers, offers a unique opportunity to examine gender-related differences in susceptibility to health effects of MWF exposure. 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 and other cancers, but can occur at up to two orders of magnitude higher concentrations in the workplace. Though we have reported strong evidence that straight MWF exposure increases the risk of bladder cancer and melanoma skin cancer in men, anticipated links with respiratory, digestive and other cancers have been less clear and we have not had sufficient power to look separately at women until now. Whereas mortality follow-up begins in 1941, 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. The sub-cohorts of 33,389 men and 4,397 women eligible for this proposed cancer study include only those workers who survived until the later start of follow-up. Occupational cohorts are often defined from a roster of active workers, so that person-time is left truncated for subjects hired prior to start of follow-up. Because we have demographic and exposure data on subjects who did not survive until the cancer registries, the incidence cohorts can be considered left censored, rather than left truncated. Left censoring presents a bias similar to left truncation, but allows for the opportunity to apply censoring weights to ensure that exposure-related risks are not underestimated. We have substantial experience applying causal g-methods to control for the healthy worker survivor effect 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. This will be the first application of these g-methods to the study of cancer incidence. 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 men and women ? in a form that can guide new exposure limits to prevent cancer.
We propose to continue our study of the health effects of metalworking fluids (MWF) in a cohort of Michigan autoworkers by highlighting cancer incidence in females, as well as males, and applying the advanced statistical methods necessary to characterize exposure-response relations without bias due to left censoring or the healthy worker survivor effect.