Mortality Update of a Cohort of Canadian Petroleum Workers.

OBJECTIVE: This study updates the mortality experience of over 25,000 workers in a large Canadian petroleum company through December 31, 2006. METHODS: Standardized mortality ratios were generated for all-cause and specific cause mortality. RESULTS: All cause and all cancer mortality were favorable compared with the general Canadian population. Cancers of previous interest were largely consistent with expectation. There is a continuing excess of mesothelioma, which is of similar magnitude as the previous update, although based on larger numbers. This excess is mostly attributable to men who died in their 50s and 60s and who worked in the refining sector. CONCLUSION: Most causes of death show mortality rates lower than the Canadian general population. Given the excess of mesothelioma observed, this study supports ongoing vigilance in asbestos exposure control programs, as refineries continue to remove asbestos from their facilities.

Risk of myeloproliferative disease and chronic myeloid leukaemia following exposure to low-level benzene in a nested case-control study of petroleum workers.

BACKGROUND: Benzene exposure has been associated with increased risk of leukaemia and myelodysplastic syndrome. Existing studies are sparse for other lymphohaematopoietic cancer subtypes, such as myeloproliferative disease (MPD) and the related chronic myeloid leukaemia (CML). We pooled data from three petroleum worker nested case-control studies to address this gap. To our knowledge, this is the first study to systematically examine the relationship between MPD and quantitative benzene exposure. METHODS: There were 28 cases and 122 matched controls for CML and 30 MPD cases with 124 matched controls. Two haematopathologists identified each case and provided a diagnosis certainty score. Blinded data-driven assessments estimated benzene exposure for each job held by study participants. Statistical analyses included conditional logistic regression and penalised smoothing splines. RESULTS: Benzene exposures were low, and mean average exposure intensity for CML cases was 0.3 ppm and for MPD cases 0.17 ppm. Categorical analyses showed no increased risk of CML or MPD with benzene exposure. There was no significantly increased risk identified for more highly exposed terminal workers. Some association was seen in spline analyses between increased risk of MPD and benzene exposure experienced in the 2-20 years before diagnosis and with peak exposures considered with cumulative exposure as a continuous variable. CONCLUSIONS: No convincing association was identified between MPD or CML and low exposure to benzene. The greater risk for exposures experienced in the 20 years before diagnosis needs investigating in more powerful studies with a wider range of exposure to benzene, and the biological plausibility further examined from a mechanistic viewpoint.

Myelodysplastic syndrome and benzene exposure among petroleum workers: an international pooled analysis.

BACKGROUND: Benzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers. METHODS: We updated three nested case-control studies from Australia, Canada, and the United Kingdom with new incident LH cancers among petroleum distribution workers through December 31, 2006, and pooled 370 potential case subjects and 1587 matched LH cancer-free control subjects. Quantitative benzene exposure in parts per million (ppm) was blindly reconstructed using historical monitoring data, and exposure certainty was scored as high, medium, or low. Two hematopathologists assigned diagnoses and scored the certainty of diagnosis as high, medium, or low. Dose-response relationships were examined for five LH cancers, including the three most common leukemia cell-types (AML, chronic myeloid leukemia [CML], and chronic lymphoid leukemia [CLL]) and two myeloid tumors (myelodysplastic syndrome [MDS] and myeloproliferative disease [MPD]). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, controlling for age, sex, and time period. RESULTS: Cumulative benzene exposure showed a monotonic dose-response relationship with MDS (highest vs lowest tertile, >2.93 vs ≤0.348 ppm-years, OR = 4.33, 95% CI = 1.31 to 14.3). For peak benezene exposures (>3 ppm), the risk of MDS was increased in high and medium certainty diagnoses (peak exposure vs no peak exposure, OR = 6.32, 95% CI = 1.32 to 30.2) and in workers having the highest exposure certainty (peak exposure vs no peak exposure, OR = 5.74, 95% CI = 1.05 to 31.2). There was little evidence of dose-response relationships for AML, CLL, CML, or MPD. CONCLUSIONS: Relatively low-level exposure to benzene experienced by petroleum distribution workers was associated with an increased risk of MDS, but not AML, suggesting that MDS may be the more relevant health risk for lower exposures.

Lung cancer incidence in Canadian petroleum workers.

OBJECTIVES: This study's purpose was to conduct a more in-depth analysis of the potential association between lung cancer, occupational exposures and smoking using data on cohort members from a Canadian petroleum company and refined statistical analyses. METHODS: Information on various exposures including asbestos and petroleum coke dust, as well as job type and operating segment were collected via manual and computerised company records. We performed life-table analyses, Poisson regression and restricted cubic splines to model exposure-response patterns while controlling for smoking status and age. Model diagnostics included the assessment of dispersion and offset parameters. RESULTS: These analyses show that lung cancer risk is strongly related to age and smoking, and to a lesser extent to province of last residence. When controlling for these covariates, there is suggestive evidence that maintenance work may also be related to lung cancer risk. Some analyses also indicate that asbestos exposure may be associated with lung cancer risk, although a clear exposure-response trend is not seen. Other exposures, including petroleum coke dust, were not strongly related to lung cancer risk, particularly when expressed as a continuous measure. CONCLUSIONS: These data suggest that maintenance work may be associated with lung cancer incidence, although exposures to the single agents studied did not emerge as strong predictors of lung cancer incidence. Maintenance work may be a surrogate for general exposures to several agents (eg, polycyclic aromatic hydrocarbons, metals, welding fumes, radiation, etc), although these results may be affected by residual confounding due to smoking or other socio-demographic factors.

Exposure assessment methods for a study of mortality and cancer morbidity in relation to specific petroleum industry exposures.

In 1987 a Canadian company implemented an exposure tracking and health information system. The exposure tracking method aligned closely with published concepts for describing workplace exposure, with over 1800 similar exposure groups being used to describe occupational exposures. The database has been actively maintained and is subject to a number of quality checks. Recently, the company initiated a cancer morbidity study, with one objective being to examine whether the exposure tracking data could be used to reconstruct exposure estimates for the cohort. Five agents--hydrogen sulfide, petroleum coke/spent catalyst, hydrocarbon solvents and fuels, hydrocarbon lubricants, and an index for exposure to operations derived from noise exposure--were selected for development of occupational exposure estimates for each cohort member. The cohort consisted of workers first employed between January 1964 and December 1994 and who were employed for at least 1 year. Work history records were associated with a similar exposure group, using human resources data and knowledge of local industrial hygienists. Only employees with >90% duration of their work history assigned were kept in the cohort (25,292 people out of a possible 25,617). For each similar exposure group inventory, the substances were identified that contributed to each of the five agents being studied. Exposure estimates before 1987 were modified using historic occupational exposure limits. Rules were created to sum the exposure from multiple substances found in any one similar exposure group. The validity of exposure estimates was tested via comparison with results documented in industrial hygiene survey reports. Industrial hygienists who were unaware of the derived exposure estimates evaluated several hundred industrial hygiene surveys and prepared benchmark information. The two lists were then evaluated for concordance, which was found to be significantly different from that occurring by chance. We conclude that the process described can create valid exposure estimates for use in epidemiology studies.

Review of the literature on benzene exposure and leukemia subtypes.

The epidemiologic literature on benzene exposure and leukemia in the MEDLINE and TOXNET databases was examined through October 2004 using the keywords "benzene", "leukemia" and "adverse health effects". This search was complemented by reviewing the reference lists from extant literature reviews and criteria documents on benzene. Published studies were characterized according to the type of industry studied and design, exposure assessment, disease classification, and control for confounding variables. Study design consisted of either cohort studies or case-control studies, which were further categorized into population-based and nested case-control studies. Disease classification considered the source of diagnostic information, whether there was clinical confirmation from medical records or histopathological, morphological and/or cytogenetic reviews, and as to whether the International Classification of Diseases (ICD) or the French-American-British (FAB) schemes were used (no studies used the Revised European-American Lymphoma (REAL) classification scheme). Nine cohort and 13 case-control studies met inclusion criteria for this review. High and significant acute myeloid leukemia risks with positive dose response relationships were identified across study designs, particularly in the "well-conducted" cohort studies and especially in more highly exposed workers in rubber, shoe, and paint industries. Risks for chronic lymphocytic leukemia (CLL) tended to show elevations in nested case-control studies, with possible dose response relationships in at least two of the three studies. However, cohort studies on CLL show no such risks. Data for chronic myeloid leukemia and acute lymphocytic leukemia are sparse and inconclusive.

An analysis of the risk of B-lymphocyte malignancies in industrial cohorts.

Among numerous studies of occupational groups with varied chemical exposures (e.g., farmers, petroleum workers, and rubber workers), some have reported excess risk for non-Hodgkin's lymphoma (NHL), multiple myeloma, and other cancers of the B-lymphocyte cell line. While not conclusive, these studies raise questions about the effects of chemical exposures on the lymphocytic versus myeloid cell lines. Almost 70 occupational cohort studies were identified that addressed B-cell cancer risks in 9 major industrial categories, in order to look for common patterns across industries. This effort was substantially limited by the inconsistent nature of lymphohematopoietic (LH) classification schemes across studies and over time, and the relative paucity of B-cell-specific results in studies for any given industry. Taking these limitations into consideration, a descriptive, graphical analysis suggested a pattern of B-cell cancer elevations in the rubber and "general chemical" industries, but no consistent patterns in petroleum production/distribution or petrochemical production. The limited data sources, which lack detail about differences in hazard and exposure for different types of products/chemicals, did not allow a comprehensive look at possible common exposures associated with B-cell cancer elevations across industries. This study suggests that evaluation of possible associations between specific chemical exposures and B-cell malignancies would require additional studies with clear and common definitions of B-cell outcomes. The article concludes by giving an example of a possible common framework for categorizing NHL, the diseases for which most classification issues arise.