LYMPHOMAS AND OCCUPATIONAL BENZENE EXPOSURE

doi:10.1016/S0140-6736(79)92022-1

The Lancet

Volume 313, Issue 8131, 30 June 1979, Pages 1394-1395

https://doi.org/10.1016/S0140-6736(79)92022-1 Get rights and content

Abstract

There was a significant excess of deaths caused by major lymphomas in men employed in occupations where benzene and/or coal tar fractions are used. The increase in risk was limited to those who were 45 years of age and older at death, an observation which is consistent with the possibility that chronic exposure might be important. Evidence from other studies suggests that benzene may adversely affect the immunological system.

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Cited by (101)

Benzene and the risk of non-Hodgkin lymphoma: A review and meta-analysis of the literature
2010, Cancer Epidemiology
Citation Excerpt :
Tests for heterogeneity within each exposure source group showed low to no evidence of heterogeneity except among studies which derived exposure from occupational codes (Fig. 1). The heterogeneity within this group was due to the increased risk reported by Vianna and Polan [10]. This study – the first to test for a relationship between NHL and benzene – has been criticised for using an inappropriate comparison group; the use of census data may not be comparable with the source data collected from death certificates.
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.
Metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, in mouse liver by alcohol dehydrogenase Adh1 and aldehyde reductase AKR1A4
2006, Toxicology and Applied Pharmacology
The reductive metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, was studied in mouse liver. Using an HPLC-based stopped assay, the primary reduced metabolite was identified as 6-hydroxy-trans, trans-2,4-hexadienal (OH/CHO) and the secondary metabolite as 1,6-dihydroxy-trans, trans-2,4-hexadiene (OH/OH).
The main enzymes responsible for the highest levels of reductase activity towards trans, trans-muconaldehyde were purified from mouse liver soluble fraction first by Q-sepharose chromatography followed by either blue or red dye affinity chromatography. In mouse liver, trans, trans-muconaldehyde is predominantly reduced by an NADH-dependent enzyme, which was identified as alcohol dehydrogenase (Adh1). Kinetic constants obtained for trans, trans-muconaldehyde with the native Adh1 enzyme showed a V_max of 2141 ± 500 nmol/min/mg and a K_m of 11 ± 4 μM. This enzyme was inhibited by pyrazole with a K_I of 3.1 ± 0.57 μM. Other fractions were found to contain muconaldehyde reductase activity independent of Adh1, and one enzyme was identified as the NADPH-dependent aldehyde reductase AKR1A4. This showed a V_max of 115 nmol/min/mg and a K_m of 15 ± 2 μM and was not inhibited by pyrazole.
Exposure to benzene and non-Hodgkin lymphoma, an epidemiologic overview and an ongoing case-control study in Shanghai
2005, Chemico-Biological Interactions
Citation Excerpt :
The epidemiologic overview presented earlier shows that there is little epidemiologic evidence supporting an association between benzene exposure and NHL. The record-linkage investigation reported by Vianna and Polan [15] was a classic example of misleading results derived from linking health data to administrative databases that were not set up for research purposes [16,18]. Another investigation suggesting an increased risk of NHL among benzene-exposed workers was based on a cohort of Chinese workers in a variety of industries involving exposures to not only benzene but also other chemicals [19].
The interest in the relationship between benzene exposure and non-Hodgkin lymphoma (NHL) appears to have been generated from a 1979 publication, which reported an increased risk of NHL among persons potentially exposed to benzene and/or coal tar fractions. More recently (1997), an increased risk of NHL was reported among 74,828 workers exposed to benzene and other chemicals in a variety of industries in China. On the contrary, no increased risk of NHL was reported in a cohort of 1,165 workers at two rubber hydrochloride plants in Ohio (US), who were exposed to extremely high levels of benzene and were found to have an increased risk of acute myeloid leukemia. In another large cohort of some 7,676 US workers exposed to benzene, no increased risk of NHL was reported. Similarly, no increased risk of NHL was reported in a combined cohort of 308,199 petroleum workers in the US, the UK, Canada, Australia, Italy and Finland, who were exposed to benzene or benzene-containing petroleum products. The lack of an association between benzene exposure and NHL in cohort studies is supported by case-control studies from the US, Canada, Italy and the UK.
To further investigate the relationship between benzene exposure and NHL, we are conducting a hospital-based case-control study in Shanghai, China. Cases are newly diagnosed NHL patients at 29 hospitals in Shanghai. For each case, two matched controls are selected among patients without any lymphatic or hematopoietic diseases at the same hospital. Demographic, employment, medical and lifestyle information is obtained through questionnaires (primary and secondary). Sources for benzene exposure information include a database of 50,000+ benzene measurements maintained by the Shanghai Municipal Institute of Public Health Supervision (IPHS), Shanghai District IPHS, walk-through surveys at factories, additional measurements at factories and reports in Chinese medical journals. Patient enrollment started in 2003 and it is estimated that the study will have 400–450 NHL cases by December 2006. Some of the occupations or industries reported among enrolled study subjects (cases and controls) with potential exposure to benzene include shoe workers, painters, mechanics or machinists, and printers. Some of the unique features of the study are discussed.
Cancer
2005, Textbook of Clinical Occupational and Environmental Medicine
Cancer cluster among police detachment personnel
2003, Environment International
An apparent cancer cluster at a police detachment in a coastal British Columbia community was investigated. Police personnel suspected that the detachment building may have been a factor. Police personnel (20 current and 154 previous employees) associated with the detachment since 1963, the date of occupancy, were traced. After all 174 cases were contacted directly, or next of kin in case of death, a total of 16 cases of cancer or suspected cancers were reported. Of these 16, eight cases of cancer were confirmed through a cancer registry. Cancers included testicular, cervical, colon, skin (including melanoma), leukemias and lymphomas with an age range of diagnosis between 22 and 44 years. There was no evidence for an underlying event, factor or condition in the police building that could be attributed to the observed cancer cases. A possible association between these cancers and the use of police traffic radar is discussed.
Investigations of benzene exposure, benzene poisoning, and malignancies in China
2002, Regulatory Toxicology and Pharmacology

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Occupational HealthLYMPHOMAS AND OCCUPATIONAL BENZENE EXPOSURE

Abstract

Am J Med

Lancet

Lancet

Lancet

Benzene and leukemia

N Engl J Med

Chronic exposure to benzene as a possible contributory etiologic factor in Hodgkin's disease

Blut

Un cas d' hemopathie benzolique tres retardee a type de lymphosarcomatose

Bull Mem Soc Méd Hôp

Occupational Health
LYMPHOMAS AND OCCUPATIONAL BENZENE EXPOSURE