Long-term health experience of jet engine manufacturing workers: III. Incidence of malignant central nervous system neoplasms.

OBJECTIVE: To explore a perceived unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven (NH), Connecticut (CT). METHODS: Subjects were 212,513 workers ever employed in 1 of 8 manufacturing facilities from 1952 to 2001 and at risk from 1976 to 2004. We identified 722 cases of CNS neoplasms mainly by tracing through 19 state cancer registries. We computed standardized incidence ratios (SIRs) based on CT state and national rates and modeled internal relative risks (RRs). RESULTS: We found overall deficits in cases for glioblastoma (275 cases, SIR = 0.77, CI = 0.68-0.87) and most other histology categories examined. NH workers had a not statistically significant overall 8% excess in glioblastoma (43 cases, SIR = 1.08, CI = 0.78-1.46). Salaried NH workers had a statistically significant twofold risk of glioblastoma compared with hourly workers (17 cases, RR = 2.04, CI = 1.15-3.57). Other subgroups of NH workers revealed elevated but not statistically significant glioblastoma risks but little evidence of an association with duration of employment or time since first employment. CONCLUSIONS: Incidence rates for glioblastoma and other malignant CNS neoplasm histologies were not elevated in the total cohort. The glioblastoma excesses observed among NH workers may reflect external occupational factors, non-occupational factors or workplace factors unique to NH unmeasured in the current study.

Methodological issues in a retrospective cancer incidence study.

The authors traced incidence of central nervous system cancer in a large occupational cohort of jet engine manufacturing workers from 1976 to 2004 in the 24 US states that comprised 95% of the cohort deaths. The cohort of approximately 224,000 employees was matched with cancer registry data; all central nervous system cancer matches were requested with their diagnostic data. This paper highlights the obstacles encountered while conducting this retrospective cancer incidence study. The authors spent approximately 700 hours completing applications and obtaining the cohort matches. Approximately 70% of the cases were identified in the state in which the facility of interest is located. In addition to the large amount of time involved, identified issues include complicated approval processes, high costs, temporal differences among the registries, and registry agency difficulty in performing the matching. Several states do not allow individual-level data to be used for research purposes. Researchers can gain important cancer incidence information by matching retrospective cohorts to multiple state cancer registries. However, they should carefully weigh the time and costs required and plan accordingly. Despite some serious obstacles, many of which are potentially resolvable, cancer incidence studies of retrospective cohorts using multiple cancer registries are feasible.

Long-term health experience of jet engine manufacturing workers: VII: occupational exposures.

OBJECTIVE: To reconstruct agent-specific occupational exposures for a cohort of jet engine manufacturing workers for use in an epidemiological mortality study. METHODS: Potential chemical and physical exposures at eight jet engine manufacturing and overhaul/repair plants were evaluated for the period 1952 to 2001. Eleven agents were selected for detailed examination, and a job-exposure matrix was constructed. RESULTS: Quantitative exposure estimates were generated for metalworking fluids, nickel, cobalt, chromium, solvents, and incomplete combustion aerosol from metalworking fluids. Qualitative exposure estimates were assigned for ionizing radiation, electromagnetic fields, polychlorinated biphenyls, and lead-cadmium. All exposures showed decreasing trends over the study period. CONCLUSIONS: The quantitative exposure levels generated in this study were lower than early contemporaneous professional practice recommendations and were similar to or lower than published data from other industries.

Long-term health experience of jet engine manufacturing workers: IX. further investigation of general mortality patterns in relation to workplace exposures.

OBJECTIVE: To evaluate mortality rates among a cohort of jet engine manufacturing workers. METHODS: Subjects were 222,123 workers employed from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,317 deaths. We computed standardized mortality ratios and modeled internal cohort rates. RESULTS: Mortality excesses reported initially no longer met the criteria for further investigation. We found two chronic obstructive pulmonary disease-related mortality excesses that met the criteria in two of eight study plants. CONCLUSIONS: At the total cohort level, chronic obstructive pulmonary disease-related categories were not related to any factors or occupational exposures considered. A full evaluation of these excesses was limited by lack of data on smoking history. Occupational exposures received outside of work or uncontrolled positive confounding by smoking cannot be ruled out as reasons for these excesses.

Long-term health experience of jet engine manufacturing workers: VI: incidence of malignant central nervous system neoplasms in relation to estimated workplace exposures.

OBJECTIVE: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures. METHODS: Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents. RESULTS: In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven. CONCLUSIONS: If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

Long-term health experience of jet engine manufacturing workers: VIII. glioblastoma incidence in relation to workplace experiences with parts and processes.

OBJECTIVE: To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed. METHODS: Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases. RESULTS: In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk. CONCLUSIONS: If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.

Long-term health experience of jet engine manufacturing workers: V. Issues with the analysis of non-malignant central nervous system neoplasms.

OBJECTIVE: We attempted to examine non-malignant central nervous system (CNS) neoplasms incidence rates for workers at 8 jet engine manufacturing facilities in Connecticut. The objective of this manuscript is to describe difficulties encountered regarding these analyses to aid future studies. METHODS: We traced the cohort for incident cases of CNS neoplasms in states where 95% of deaths in the total cohort occurred. We used external and internal analyses in an attempt to obtain the true risk of non-malignant CNS in the cohort. Because these analyses were limited by data constraints, we conducted sensitivity analyses, including using state driver's license data to adjust person-year stop dates to help minimize underascertainment and more accurately determine cohort risk estimates. RESULTS: We identified 3 unanticipated challenges: case identification, determination of population-based cancer incidence rates, and handling of case underascertainment. These factors precluded an accurate assessment of non-malignant CNS neoplasm incidence risks in this occupational epidemiology study. CONCLUSIONS: The relatively recent (2004) mandate of capturing non-malignant CNS tumor data at the state level means that, in time, it may be possible to conduct external analyses of these data. Meanwhile, similar occupational epidemiology studies may be limited to descriptive analysis of the non-malignant CNS case characteristics.

Long-term health experience of jet engine manufacturing workers: II. Total and cause-specific mortality excluding central nervous system neoplasms.

OBJECTIVE: As part of an exploratory investigation of an unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven, Connecticut (CT), we examined total and cause-specific (excluding central nervous system neoplasms) mortality rates at eight of the company's CT facilities. METHODS: Subjects were 223,894 workers ever employed in one or more of the manufacturing facilities from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,701 deaths. We computed standardized mortality ratios (SMRs) based on US and CT state rates and modeled internal cohort rates. RESULTS: We observed overall deficits in deaths based on national and state comparisons from all causes, all cancers and most of the cause of death categories examined. State comparisons revealed statistically significant excesses in deaths greater than 25% for kidney cancer (68 deaths, SMR = 1.30, CI = 1.01-1.65) and "other non-malignant respiratory disease" (291 deaths, SMR = 1.27, CI = 1.13-1.42) among subjects employed only at North Haven, and for bronchitis (713 deaths, SMR = 1.28, CI = 1.18-1.37) among all hourly workers. These excesses occurred mainly among short-term workers and hourly workers. CONCLUSIONS: We found no evidence of elevated mortality risks for all causes combined, all cancers combined and most of the causes of death categories examined. The pattern of findings for kidney cancer, bronchitis and other non-malignant respiratory disease, based on currently available data, suggests these excesses may be due to non-occupational risk factors or to external occupational factors. We will investigate these excesses further when detailed work history and exposure data from the companion exposure assessment project become available.

Long-term health experience of jet engine manufacturing workers: I. Mortality from central nervous system neoplasms.

OBJECTIVE: In response to an unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven (NH), Connecticut (CT), we examined mortality rates from central nervous system (CNS) neoplasms at NH and seven other company facilities. METHODS: Subjects were 223,894 workers ever employed in one or more of the company's eight CT manufacturing facilities from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,701 deaths. We computed standardized mortality ratios (SMRs) based on US and CT state rates and modeled internal relative risks (RRs). RESULTS: State comparisons revealed overall deficits in deaths from all CNS neoplasms (606 deaths, SMR = 0.84, confidence interval [CI] = 0.78 to 0.91), including all malignant (462 deaths, SMR = 0.87, CI = 0.79 to 0.95), all benign (23 deaths, SMR = 0.65, CI = 0.41 to 0.98), and all unspecified (121 deaths, SMR = 0.79, CI = 0.65 to 0.94). Not statistically significant excesses in deaths from all malignant brain neoplasms were found among subjects who worked only at NH (49 deaths, SMR = 1.11, CI = 0.82 to 1.47) or partly at NH (24 deaths, SMR = 1.04, CI = 0.67 to 1.55) compared with deficits in non-NH plant groups. In the combined NH plant groups, we found not statistically significant higher risks of malignant brain neoplasms for salaried workers, older hires and the most recent time period, but no association with duration of employment or time since first employment. CONCLUSIONS: Total cohort mortality rates for malignant, benign or unspecified CNS neoplasms were not elevated relative to the US and CT general populations. The malignant brain neoplasm excesses in certain subgroups of workers from NH may reflect external occupational factors, nonoccupational factors or workplace factors unique to NH that were not measured in the current study. We will explore reasons for the NH excesses and examine specific types of brain neoplasms (eg, glioblastoma) in our companion cancer incidence, case-control and exposure assessment studies.