Benzene and the risk of non-Hodgkin lymphoma: A review and meta-analysis of the literature

Abstract

Benzene, an accepted leukemogen, has been suggested to cause other hemato- and lymphopoietic cancers. Here we review the published literature for non-Hodgkin lymphoma (NHL) and occupational exposure to benzene. Six cohorts, sixteen case–control studies and two studies of other designs were identified through keyword searches of bibliographic databases. Twenty-two of twenty-four studies found no association between NHL and ever exposed to benzene compared to never; a random-effects meta-analysis gave a pooled risk estimate of 1.11 (95% confidence interval 0.94–1.30). Our finding of no effect agrees with one of two previous meta-analyses. The other meta-analysis examined if high benzene exposure increased NHL risk but a lack of consistent exposure categories within the same metric should have precluded pooling risks by exposure level. Instead, we reviewed whether dose–response relationships existed. The best available data came from six studies where exposure was estimated from historical measurements and on the whole, no trends in risks of NHL with rising cumulative, average, peak, or duration of benzene exposure were found. NHL is a heterogeneous group of malignancies and although less well-studied, benzene was not associated with any NHL subtype. In conclusion, benzene at either low or high doses does not increase the risk of NHL.

Introduction

Benzene, first isolated from compressed oil gas by Michael Faraday in 1825, has been utilised in numerous commercial applications since its industrial production in the mid-nineteenth century [1], [2]. By the 1920s, benzene was widely used as an industrial solvent, but some workers were experiencing adverse health effects and even death following exposure to air concentrations estimated at 500 parts per million (ppm, equivalent to 1600 mg/m³) or above [3], [4]. In 1928, Delore and Borgomano reported a case of acute lymphoblastic leukemia in a worker exposed to benzene for five years, and later, occupationally exposed cohorts were found to have an increased incidence of acute leukemia [5], [6], [7], [8]. Sufficient evidence had now accumulated for the International Agency for Research on Cancer (IARC) to conclude, in 1982, that “the relationship between benzene and the development of acute myelogenous leukaemia has been established in epidemiological studies” and to deem benzene carcinogenic to man [9].

With the association between benzene exposure and leukemia accepted, there has been some suggestion that benzene may cause other hematopoietic and lymphatic cancers. For non-Hodgkin lymphoma (NHL), interest in the relationship with benzene began with Vianna and Polan's report in 1979 of a positive association [10] and subsequently numerous epidemiological studies investigated this hypothesis. To summarize and collate the published evidence for NHL, several reviews [11], [12], [13], [14], [15] and meta-analyses have been conducted [16], [17] but a consensus on whether or not benzene is associated with NHL has not been reached. Here we review the epidemiological literature for NHL and occupational exposure to benzene, and conduct meta-analyses to assist in the interpretation of the evidence.