Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

Abstract

Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case-control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL).

Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines.

Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers.

Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone.

Figure 1

Penalised splines for benzene exposure metrics for AML and sensitivity analyses on disease and exposure history certainty. Log odds ratio of risk of LH cancer subtype as a smooth function of the binary logarithm of cumulative (p.p.m.-years +0.001), average (p.p.m.), and maximum exposure (p.p.m.). In panel D, log odds ratios are plotted against duration on an additive scale. More certain cases refer to those with medium or high case certainty, and subjects with more certain exposure history refer to those with medium or high job history confidence scores. (A) AML: Cumulative benzene exposure (p.p.m.-years). (B) AML: average intensity of benzene exposure (p.p.m.). (C) AML: maximum intensity of benzene exposure (p.p.m.). (D) AML: duration of employment (years).