Leukemia risk in caprolactam workers exposed to benzene

Swaen, Gerard M. H.; Scheffers, Theo; Cock, J. de; Slangen, J. J. M.; Drooge, H. van

doi:10.1016/j.annepidem.2004.03.007

Cited by 16 publications

(8 citation statements)

References 18 publications

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“…We qualitatively explored the quantitative exposure–response relation between benzene and MM. Two of eight exposure assessment quality category A studies reported an increase in RR with increasing cumulative exposure (Collins et al 2003; Rinsky et al 2002); in two studies the authors reported no clear trend of RRs for MM with increasing cumulative exposure to benzene (Atkinson et al 2001; Schnatter et al 1996); and four studies did not report on the quantitative relation between cumulative exposure to benzene and MM (Bloemen et al 2004; Swaen et al 2005; Wong 1987b; Yin et al 1996). Therefore, although the evidence for an association between “any occupational benzene exposure” versus “background benzene exposure” and the RR of MM appears to be consistent, the evidence for an exposure–response relation between benzene and MM is more ambiguous.…”

Section: Discussionmentioning

confidence: 99%

Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions

Vlaanderen

Lan

Kromhout

et al. 2011

Environ Health Perspect

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BackgroundThe use of occupational cohort studies to assess the association of benzene and lymphoma is complicated by problems with exposure misclassification, outcome classification, and low statistical power.ObjectiveWe performed meta-analyses of occupational cohort studies for five different lymphoma categories: Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL).Data extractionWe assessed three study quality dimensions to evaluate the impact of study quality variations on meta-relative risks (mRRs): stratification by the year of start of follow-up, stratification by the strength of the reported acute myelogenous leukemia association, and stratification by the quality of benzene exposure assessment.Data synthesismRRs for MM, ALL, and CLL increased with increasing study quality, regardless of the study quality dimension. mRRs for NHL also increased with increasing study quality, although this effect was less pronounced. We observed no association between occupational benzene exposure and HL.ConclusionsOur meta-analysis provides support for an association between occupational benzene exposure and risk of MM, ALL, and CLL. The evidence for an association with NHL is less clear, but this is likely complicated by the etiologic heterogeneity of this group of diseases. Further consideration of the association between benzene and NHL will require delineation of risks by NHL subtype.

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Section: Discussionmentioning

confidence: 99%

Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions

Vlaanderen

Lan

Kromhout

et al. 2011

Environ Health Perspect

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“…However, systematic differences in exposure assessment strategies between studies might have contributed to the between-study heterogeneity. Because all included studies assessed exposure retrospectively based on a relatively limited set of exposure measurements, exposure estimation in these studies was based partly on decision rules to extrapolate exposure measurements to time periods and exposure circumstances for which no measurements were available (Bloemen et al 2004; Costantini et al 2003; Glass et al 2003; Hayes et al 1997; Rinsky et al 2002; Rushton and Romaniuk 1997; Schnatter et al 1996; Swaen et al 2005; Wong 1987). The significant amount of expert judgment that goes into these decision rules makes it conceivable that systematic differences in exposure assessment may exist between studies.…”

Section: Discussionmentioning

confidence: 99%

“…The studies selected for the meta-regression were also different with regard to the definition of the reference population that was used. The cohort studies assumed “background (environmental) exposure” in their reference populations (Bloemen et al 2004; Costantini et al 2003; Hayes et al 1997; Rinsky et al 2002; Swaen et al 2005; Wong 1987). Typical daily environmental exposure to benzene can range up to 0.2 ppm, which, over a 70-year life span, accumulates to a maximum of 14 ppm-years of cumulative exposure (Johnson et al 2007).…”

Section: Methodsmentioning

confidence: 99%

“…In the first step, we assigned a specific cumulative exposure estimate to each risk estimate. It is common practice to report only the boundaries of the exposure categories used in an exposure–response analysis, and this was the case for all included studies except the Swaen study, which reported an average mean exposure (Greenland and Longnecker 1992; Swaen et al 2005). To estimate the mean exposure for the assigned exposure categories, we assumed a log-normal distribution for the cumulative exposure for each study.…”

Section: Methodsmentioning

confidence: 99%

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Flexible Meta-Regression to Assess the Shape of the Benzene–Leukemia Exposure–Response Curve

Vlaanderen

Portengen

Rothman

et al. 2010

Environ Health Perspect

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BackgroundPrevious evaluations of the shape of the benzene–leukemia exposure–response curve (ERC) were based on a single set or on small sets of human occupational studies. Integrating evidence from all available studies that are of sufficient quality combined with flexible meta-regression models is likely to provide better insight into the functional relation between benzene exposure and risk of leukemia.ObjectivesWe used natural splines in a flexible meta-regression method to assess the shape of the benzene–leukemia ERC.MethodsWe fitted meta-regression models to 30 aggregated risk estimates extracted from nine human observational studies and performed sensitivity analyses to assess the impact of a priori assessed study characteristics on the predicted ERC.ResultsThe natural spline showed a supralinear shape at cumulative exposures less than 100 ppm-years, although this model fitted the data only marginally better than a linear model (p = 0.06). Stratification based on study design and jackknifing indicated that the cohort studies had a considerable impact on the shape of the ERC at high exposure levels (> 100 ppm-years) but that predicted risks for the low exposure range (< 50 ppm-years) were robust.ConclusionsAlthough limited by the small number of studies and the large heterogeneity between studies, the inclusion of all studies of sufficient quality combined with a flexible meta-regression method provides the most comprehensive evaluation of the benzene–leukemia ERC to date. The natural spline based on all data indicates a significantly increased risk of leukemia [relative risk (RR) = 1.14; 95% confidence interval (CI), 1.04–1.26] at an exposure level as low as 10 ppm-years.

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“…Regulatory agencies, epidemiological studies and peer-reviewed medical literature typically cite cumulative benzene exposures in excess of 40 ppm years as the minimum exposure required to potentially cause secondary MDS/AML [2, 47, 48]. However, exposure levels well in excess of these values may not result in a statistically significant excess incidence of AML [49, 50]. …”

Section: Discussionmentioning

confidence: 99%

Temozolomide-Induced Myelodysplasia

Natelson

Pyatt²

2010

Advances in Hematology

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A patient who had received temozolomide (TMZ) as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS). TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT) for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML) is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

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Leukemia risk in caprolactam workers exposed to benzene

Cited by 16 publications

References 18 publications

Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions

Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions

Flexible Meta-Regression to Assess the Shape of the Benzene–Leukemia Exposure–Response Curve

Temozolomide-Induced Myelodysplasia

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