Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, Berkeley, CA, USA; Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
Lancet Planet Health. 2021 Sep;5(9):e633-e643. doi: 10.1016/S2542-5196(21)00149-2. Epub 2021 Aug 25.
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.
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.
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.
Our findings suggest a causal link between benzene exposure and non-Hodgkin lymphoma, especially for diffuse large B-cell lymphoma.
National Institute of Environmental Health Sciences.
非霍奇金淋巴瘤是一组具有未解决病因的异质性癌症，尽管风险因素包括接触有毒化学物质的环境暴露。虽然无处不在的污染物苯是一种已确定的白血病成因，但它引起非霍奇金淋巴瘤的潜力一直存在广泛争议。我们旨在通过评估广泛的队列和病例对照研究，使用电子系统评价来检查苯暴露与人类非霍奇金淋巴瘤之间的潜在联系。
我们对所有评估苯暴露与非霍奇金淋巴瘤之间关系的合格人类流行病学研究进行了全面的系统评价和荟萃分析。我们在 2019 年 6 月 5 日之前在 PubMed 和 Embase 数据库中查询了相关文章，并应用 SysRev 平台进行研究选择。所有报告了苯暴露特定非霍奇金淋巴瘤风险估计值的经过同行评审的人类队列和病例对照研究均符合纳入标准。未确定特定苯暴露的工业或职业类型计算相对风险 (RR)、将非霍奇金淋巴瘤与其他癌症类型结合起来或报告许多不同溶剂暴露的研究被排除在外。从每项研究中，两名研究人员独立提取研究设计、地点、年份、样本量、参与率、年龄、性别、病例和对照来源、诊断、组织学验证、暴露评估、结果、调整和统计分析信息，随后评估了研究质量。我们使用固定效应和随机效应模型计算荟萃分析相对风险 (meta-RR) 和置信区间，并评估发表偏倚。
我们的搜索产生了 2481 篇文章。在筛选和去除重复项后，我们的荟萃分析纳入了 20 项病例对照研究和 8 项队列研究，共纳入了 9587 名非霍奇金淋巴瘤患者。当数据可用时，我们报告了高暴露组中风险增加了 33%（meta-RR 1·33 [95%CI 1·13-1·57]，n=28）。在提供高暴露个体特定结果的研究中，meta-RR 上升至 1·51（1·22-1·87，n=18）。特别是，我们报告了这种风险在弥漫性大 B 细胞淋巴瘤（非霍奇金淋巴瘤的主要亚型）中增加了一倍（1·67 [1·01-2·77]）。我们还检测到滤泡性淋巴瘤（1·47 [0·95-2·27]）和毛细胞白血病（1·77 [0·99-3·16]）的风险增加，但无统计学意义。漏斗图、Egger 检验（p=0·77）和 Begg 检验（p=0·98）均未显示出发表偏倚的证据。我们评估了因果关系的主要方面，并发现有证据支持将因果关系归因于所有 Hill 考虑因素。
我们的研究结果表明，苯暴露与非霍奇金淋巴瘤之间存在因果关系，特别是对于弥漫性大 B 细胞淋巴瘤。
美国国家环境卫生科学研究所。
