As expected, mesothelioma deaths were more evident in maintenance and operations jobs. Workers classified as “operations” had no other notable findings for mortality, with an overall SMR of 0.72 (95% CI = 0.65 to 0.80). On the contrary, workers in the maintenance category showed a slightly higher overall cancer mortality rate than expected [95 observed vs 86.5 expected, SMR = 1.10 (95% CI = 0.89 to 1.34)]. However, the total SMR was only 0.77 (95% CI = 0.67 to 0.88). A nonstatistically significant excess of bladder cancer (5 observed vs 1.7 expected) was observed in maintenance workers.
Distribution jobs showed an overall SMR of 1.00; thus, the expected “healthy worker effect” was not displayed in these workers. This was due to small but notable excesses in the most common causes of death. The SMR for all circulatory diseases was 1.19, while moderate excesses that were not typical of healthy employed populations were present for cerebrovascular disease: 6 versus 4.3, SMR = 1.39 (95% CI = 0.51 to 3.02) and acute myocardial infarction: 20 versus 15.7, SMR = 1.27 (95% CI = 0.78 to 1.96). However, neither SMR was statistically significant. Also, noteworthy was the SMR for motor vehicle accidents in these jobs (SMR = 1.87, 95% CI = 0.86 to 3.55), many of whom are drivers.
Mortality by Exposure Status
Table 5 summarizes SMRs according to a general indicator of exposure to any operations present across jobs and operating segments. Persons classified as nonexposed in Table 5 were never in an exposed job (ie, exclusively nonexposed). A worker who had any portion of their work history in any exposed job was classified as exposed.
There were still significant deficits in all-cause (SMR = 0.74) and all-cancer (SMR = 0.84) in exposed workers, but each SMR was higher than that in nonexposed workers (SMRs = 0.62 and 0.73 for all causes and all cancers, respectively). Mesothelioma was significantly elevated in exposed workers (SMR = 3.53, 95% CI = 1.30 to 7.69), while other nonsignificant elevations were seen for bladder cancer (SMR = 1.25, 95% CI = 0.60 to 2.29), rectal cancer (SMR = 1.12, 95% CI = 0.60 to 1.91), and air and space transport accidents (SMR = 1.61, 95% CI = 0.59 to 3.49). Notably, leukemia, colon cancer, NHL, and lung cancer were all below expectation. There were five AML cases resulting in an SMR of 1.00.
SMRs in nonexposed workers were generally unremarkable, with the exception of 10 ALS cases, which was a significant excess (SMR = 2.48, 95% CI = 1.19 to 4.56). Other nonsignificant elevations were observed for Hodgkin disease based on five cases (SMR = 2.42, 95% CI = 0.79 to 5.64) and follicular lymphoma based on nine cases (SMR = 1.30, 95% CI = 0.60 to 2.47).
Mortality by Hire Date
In order to assess time trends for different diseases, we also examined the cohort by hire date (1964 to 1974) and 1975+ (see Table S-1, Supplemental Digital Content 1, http://links.lww.com/JOM/A493). These two periods resulted in a similar number of expected deaths. Overall mortality SMRs decreased from 0.70 to 0.68 for the earlier versus later higher groups, likely to be a reflection of the healthy worker effect wearing off, as most of the decrease was due to circulatory diseases (SMR = 0.70 and 0.62) for earlier and later hire periods, respectively. Malignant neoplasms showed a relatively constant SMR over the earlier and later hire periods (SMR = 0.79 and 0.77, respectively). Mesothelioma risk had a significantly raised SMR of 5.14, based on six deaths in the 1975+ hire group. Some a priori’ causes of death showed a modestly raised (nonsignificant) SMR in the earlier time period only, including follicular NHL (SMR = 1.27 based on 11 cases), AML (SMR = 1.36 based on seven cases), and multiple myeloma/immunoproliferative diseases (SMR = 1.14 based on eight cases). In addition, all central nervous system tumors (the vast majority being brain cancer) showed a higher SMR in the early hire period (SMR = 1.24 based on 25 cases). In contrast, a few causes of death showed a moderately raised, nonsignificant SMR only in the later hire period, including malignant neoplasms of the rectum and rectosigmoid junction (SMR = 1.15 based on 10 cases) and ovary (SMR = 1.62, based on nine cases).
The tenth revision of the ICD, in effect from 2000, designates a single code for mesothelioma; thus, mortality and incidence reporting are less complicated. As excess mesothelioma has been noted previously in this cohort, we also examined death certificates that could contain the diagnosis in previous versions of the ICD, as we did in the previous updates of this cohort.9,11,12 This yielded five additional cases of mesothelioma, four of which were noted in the last update. In addition, the cohort was matched to cancer registry files maintained by SC. This yielded a sixth additional case of mesothelioma. These six cases, along with the nine cases identified from 2000 forward, yielded 15 cases of mesothelioma. Canadian rates assembled in the same manner as case ascertainment techniques yielded an expected number of 5.4 cases for a standardized incidence ratio (SIR) of 2.79 (95% CI = 1.56 to 4.60) (Table 6).15 Subtracting the cases observed in the previously studied observation period yields 11 cases observed versus 4.12 expected for an SIR of 2.67. As previously noted, the mortality-only cases observed from year 1999 forward yielded nine cases and an SMR of 3.27 (95% CI = 1.50 to 6.21).
These 15 cases were further reviewed. As for jobs and duration employed, 10 were in maintenance or operations jobs and worked from 11 to 32 years. As mesothelioma often develops decades after first exposure, the time between death/incidence and first employment was examined. Less than five subjects had a 10 to 14-year interval. Most had either a 15 to 24-year or 25 to 38-year interval. All subjects died or were diagnosed in their 50s and 60s; 10 at ages 50 to 59 years, and five at ages 61 to 63 years. Eleven of the 15 cases were employed in the refinery operating segment. There was only 1.0 expected case in the refinery segment, for a significant SIR of 10.9 (95% CI = 5.45 to 19.5).
We also examined SMRs for mesothelioma by age at hire, as employees hired later may have had exposure in other industries (see Table 6). Of the nine mortality cases, five were hired between ages 25 and 35 years (SMR = 4.89, 95% CI = 1.59 to 11.41). This analysis indicates that mesothelioma cases had some potential for exposures before employment in this company.
Lost to Follow-up
We needed to use a stratified random sampling technique to select 3564 lost to follow-up (LTF) employees. SC had determined that this was the correct number of LTF, but privacy laws prevented their direct identification. Instead, we examined DLO status in the original 6171 LTF employees and selected the 3564 employees to reflect this DLO distribution. We suspected that this strategy would yield the most similar overall SMR to an SMR calculated using the DLO for the 6171 employees. To examine this directly, we computed overall (all causes) and cancer SMRs for two additional scenarios, which we believed represented two extremes: (1) using the original 6171 workers as LTF and removing them from follow-up on their DLO (to produce a minimum number of person-years at risk, hence a lower expected number of deaths and higher SMR), and (2) treating all LTF workers as alive until the end of the study (to produce a maximum number of person-years at risk, hence a larger expected number of deaths and lower SMR). Strategy (1) could be justified, as it represents the usual treatment of LTF, while strategy (2) could be justified by the high sensitivity of the Canadian Mortality Database used by SC to identify deaths.16 Results are summarized in Table 7.
These results show that the all-cause SMR for the baseline scenario (3564 LTF) is within 1.4% of the all-cause SMR, which treats all 6171 employees as LTF on their DLO. On the contrary, treating all LTF employees as alive until the end of the study would have reduced the SMR by 7.7% (from 0.690 to 0.637). Cancer SMRs show similar percent changes.
Finally, as the sensitivity of CMDB has been tested for its ability to identify deaths, one could also assume that this sensitivity (97.6%) applies to this cohort. This would predict that 1710, rather than 1669 deaths occurred. Applying the 1710 deaths to strategy (2) would yield an SMR of 0.653, a 5.4% lower SMR than the baseline approach.
This mortality update for a large Canadian cohort of petroleum workers was based on 16% more workers and 78% additional person-years of observation, allowing a better assessment of risks in this population. However, this is still a young population; thus, the accuracy of risk estimation, especially for rarer causes of death, is still relatively low. The percentage of deaths increased from 2% to 5.7% in this update. We believe it is advantageous to study inception cohorts (in this case, workers hired in 1964 or later) to improve the applicability to current workplace settings and to lessen the possibility of survivor bias influences on the results.17
As in many occupational cohort studies, mortality rates among working employees were compared with general population mortality rates; thus, the well-known healthy worker effect is probable. As this cohort is young, the healthy worker effect is greater, as more workers were close to their “selection date,” which assured a health status sufficient to apply for and be selected for employment. Thus, even moderate, nonsignificant excesses should be viewed more critically for these workers.
While effects of gender and time period were controlled, we had no additional information on lifestyle habits such as drinking and smoking, which can affect mortality from several diseases. The study is also limited by its reliance on surrogates of exposure (eg, duration of employment, operating segment, job type, and general exposure to operations), and as such, excesses restricted to employees only exposed to select compounds may be missed.
Another limitation of this study is the potential LTF for 3564 workers. This is a somewhat larger percentage than usual. We not only used the Canadian Mortality Database, but also used the US NDI to identify deaths to account for people emigrating from Canada to the US who subsequently died. We also benefited from alive tracing performed at SC, which did reduce the number of LTF, but was somewhat compromised by an inability to directly identify which employees were successfully traced. Instead, we needed to select remaining LTF employees utilizing a stratified random sampling approach. We performed sensitivity analyses on this aspect of the study and showed that our estimate of the total SMR was likely to be bounded by an error from -1.4% to +7.7%. We proffer two reasons why the LTF percent is somewhat higher than normal: (1) there could be an increase in movement of workers between this Canadian affiliate and other affiliates from the same company outside of the US, and (2) there could be an increase in the number of short-term workers, as younger persons are frequently more mobile than in years past. Subsequent updates of this cohort will need to employ even more rigorous tracing techniques to limit LTF to more customary levels.
Cancer incidence data were requested for this study but were found to be unreliable, apparently due to the multiple ICD revisions these data cover. We hope to resolve this with Statistics Canada so that future analyses can examine incident cancers.
The mortality findings in the cohort overall continue to show favorable results, with an all-cause SMR of 0.69, slightly higher than the 0.65 measured in the previous update.12 We expect that the all-cause SMR will continue to increase, as the survival advantage of initial employment selection wears off. Decreased mortality was primarily due to respiratory and circulatory diseases (especially acute myocardial infarction), which are commonly noted as most affected by the healthy worker selection effect. There were also very low SMRs for acquired immune deficiency syndrome and infectious and parasitic diseases.
For most a priori causes, results were not significantly elevated. Leukemia, NHL, and multiple myeloma showed unremarkable results, which is in agreement with most of the literature.18 Malignant melanoma, which had been elevated in upstream workers in an earlier update of this cohort,9 showed no excess risk in this update. Kidney, colon, and brain cancer were also not elevated for the full cohort or any subgroup examined.
In the last update, we reported an excess of gall bladder cancer based on less than five cases.12 The present update found no new gall bladder cancer cases, while the expected number increased to 4.9.
The single finding that showed a clear excess in risk was for mesothelioma. With an additional follow-up of this inception cohort, the mesothelioma risk in workers hired post-1964 is clearer (Table 6). Overall, the present cohort found 11 additional cases for an overall SIR of 2.7915 through 2006.
This two to three-fold risk of mesothelioma continues to persist despite continued attention in the company on asbestos exposure control. The risk is higher for maintenance and operations workers, and in the refining sector, where there is more potential for asbestos exposure. Approximately one-third of the mesothelioma cases had latency periods from first employment between 25 and 38 years, which translates to first exposures between 1968 and 1981. Although the risk of mesothelioma was expected to decrease by 2006, we did note that most decedents started work with the company at an age which suggests that they were previously employed elsewhere. If they were employed in prior jobs with asbestos exposure, the latency observed in this cohort could be artificially shortened.
A two-fold nonsignificant elevation of ALS was associated with a previous update of this study.11 This update again reports a nonsignificant elevation of ALS, based on 15 cases (SMR = 1.70), which did not quite reach statistical significance. The etiology of ALS is largely unknown.19,20 It appears that there is no clustering of ALS risk in this study by operating segment. A significant excess of ALS was found in nonexposed workers, which argues against an occupational etiology.
Other findings, some of which did not achieve statistical significance, should not be ignored, as the healthy worker effect is likely operating in this population. A near significant SMR for motor vehicle accidents among distribution workers likely reflects increased time in motor vehicles. The fact that maintenance workers show an all-cancer SMR greater than 1 is also unusual in an employed population. Bladder cancer rates should be monitored in this group, as they are subject to unique work environments (eg, welding, degreasing, etc).
In summary, this study yielded several useful insights on risks for this large Canadian cohort of petroleum workers. The clearest finding was a continuing excess of mesothelioma, which was predicted to decrease in this update. The excess concentrated in refinery workers and maintenance trades, who have a higher potential for asbestos exposure. A nonsignificant excess of ALS was also noted, which achieved significance only in workers not exposed to operations. A nonsignificant excess of motor vehicle traffic accidents in distribution workers may have an occupational link that should be monitored. Continued surveillance of this cohort is expected to yield more insight on these findings.
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Canada; Canadian; cause of death; mesothelioma; mortality; occupational cohort; petroleum workers
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