The health watch case-control study of leukemia and benzene: the story so far

A case-control study nested in the Health Watch cohort of petroleum industry workers, investigated whether the excess of lymphohematopoetic cancers, identified among male members of the Health Watch cohort, was associated with benzene exposure. Cases of non-Hodgkin's lymphoma (n = 31), multiple myeloma (n = 15), and leukemia (n = 33) were identified between 1981 and 1999. Cases were age-matched to five controls. Exposure was retrospectively estimated for each occupational history using an algorithm in a relational database. Benzene exposure measurements, supplied by Australian petroleum companies, were used to estimate exposure for specific tasks. The tasks carried out within the job, the products handled, and the technology used, were identified from interviews with contemporary colleagues. More than half of the subjects started work after 1965 and had an average exposure period of 20 years. Exposure was low, 85% of the cumulative exposure estimates were <10 ppm years. Matched analyses showed that non-Hodgkin's lymphoma and multiple myeloma were not associated with benzene exposure. Leukemia risk, however, was significantly increased for the subjects with greater than 16 ppm years cumulative exposure, odds ratio (OR) 51.9 (5.6-477) or with greater than 0.8 ppm intensity of highest exposed job. Cumulative exposures were similar to those found in comparable studies. The inclusion of occasional high exposures, for example, as a result of spillages, reduced the ORs, when the exposure was treated as either a continuous or a categorical variable. Our data demonstrate a strong association between leukemia and modest benzene exposure. The choice of cut-point and reference group has a marked effect on the ORs, but does not change the overall conclusions.