Benzene exposure and non-Hodgkin lymphoma: a systematic review and meta-analysis of human studies

Abstract

Background Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental exposures to toxic chemicals. Although the ubiquitous pollutant benzene is an established leukemogen, its potential to cause non-Hodgkin lymphoma has been widely debated. We aimed to examine the potential link between benzene exposure and risk of non-Hodgkin lymphoma in humans by evaluating a wide array of cohort and case-control studies using electronic systematic review.Methods We did a comprehensive systematic review and meta-analysis of all qualified human epidemiological studies that assessed the relationship between benzene exposure and non-Hodgkin lymphoma. We queried the PubMed and Embase databases for relevant articles published before June 5, 2019, and applied the SysRev platform for study selection. All peer-reviewed human cohort and case-control studies that reported non-Hodgkin lymphoma risk estimates specifically for benzene exposure were eligible for inclusion. Studies that calculated relative risks (RRs) for industries or job types without identifying those specifically exposed to benzene, that combined non-Hodgkin lymphoma with other cancer types, or that reported many different solvent exposures together were excluded. From each study, two investigators independently extracted information on the study design, location, years, sample size, participation rates, age, sex, sources of cases and controls, diagnosis, histological verification, exposure assessment, results, adjustment, and statistical analysis, and subsequently assessed study quality. We calculated the meta-analysis relative risk (meta-RR) and CIs using the fixed effect and random effect models, as well as assessing publication bias.Findings Our search yielded 2481 articles. After screening and removal of duplicates, 20 case-control studies and eight cohort studies were included in our meta-analysis, which included a total of 9587 patients with non-Hodgkin lymphoma. We reported an increased meta-relative risk (meta-RR) of 33% in highly exposed groups, when data were available (meta-RR 1•33 [95% CI 1•13-1•57], n=28). The meta-RR rose to 1•51 (1•22-1•87, n=18) in the studies that provided results specifically for highly exposed individuals. In particular, we reported a doubling of this risk for diffuse large B-cell lymphoma, a major non-Hodgkin lymphoma subtype (1•67 [1•01-2•77]). We also detected increased risks for follicular lymphoma (1•47 [0•95-2•27]) and hairy cell leukaemia (1•77 [0•99-3•16]), though they were not statistically significant. Funnel plot, Egger's test (p=0•77) and Begg's test (p=0•98) did not show evidence of publication bias. We evaluated the major aspects of causal inference and found evidence to support all the Hill considerations for assigning causation.Interpretation Our findings suggest a causal link between benzene exposure and non-Hodgkin lymphoma, especially for diffuse large B-cell lymphoma.

Risk of Cancer in Children of Parents Occupationally Exposed to Hydrocarbon Solvents and Engine Exhaust Fumes: A Register-Based Nested Case–Control Study from Sweden (1960–2015)

“…ORs did not vary by the degree of exposure (higher/lower). In line with a small Swiss study, 7 neither benzene nor PAH, two potent aromatic hydrocarbon carcinogens in the index individual, 37 appeared to be responsible for the observed association for non-Hodgkin lymphomas in the offspring. On the other hand, benzene and PAH were strongly associated with a higher risk of Hodgkin lymphoma.…”

Health effects of exposure to indoor volatile organic compounds from 1980 to 2017: A systematic review and meta‐analysis

“…Except for cardiovascular diseases, the outcomes for which there are data contribute little to the total loss of disability adjusted life years (DALYs). 84 Some diseases for which strong associations with VOC exposure have been reported in occupational exposure conditions [31][32][33][34]36,37,78 have not been studied at lower exposures in civil buildings. These include such diseases as non-Hodgkin's lymphoma, kidney cancer, and nasopharyngeal cancer.…”

“…Another reason is that most epidemiological research on VOC exposure has focused on occupational exposure for workers, where the exposure concentrations are much higher than those in residences, office buildings, or schools. For instance, the associations between benzene and leukemia, 29,30 multiple myeloma, 31 or non-Hodgkin lymphoma, [32][33][34] and the associations between trichloroethylene and kidney or liver cancer [35][36][37] have been studied among workers, but whether the associations are still significant for low exposure in civil buildings remains unknown. Even though there has been some research on health effects of VOC exposure in civil buildings, [38][39][40][41][42][43] these are often case-control studies or cross-sectional studies, with a small sample size, self-reported health outcomes, and non-specific exposure levels.…”

Screening of Adverse Prognostic Factors and Construction of Prognostic Index in Previously Untreated Concurrent Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

“…Follicular lymphoma (FL) is a common non-Hodgkin lymphoma (NHL) subtype, contributing to more than one-fifth of NHL cases in Western nations [ 1 , 2 ]. It is a diverse category of cancer that arises from germinal center B cells' centrocytes and centroblasts [ 3 ].…”