Abstract

Background:

The genotoxicity of benzene has been investigated in dozens of biomonitoring studies, mainly by studying (classical) chromosomal aberrations (CAs) or micronuclei (MN) as markers of DNA damage. Both have been shown to be predictive of future cancer risk in cohort studies and could, therefore, potentially be used for risk assessment of genotoxicity-mediated cancers.

Objectives:

We sought to estimate an exposure–response curve (ERC) and quantify between-study heterogeneity using all available quantitative evidence on the cytogenetic effects of benzene exposure on CAs and MN respectively.

Methods:

We carried out a systematic literature review and summarized all available data of sufficient quality using meta-analyses. We assessed the heterogeneity in slope estimates between studies and conducted additional sensitivity analyses to assess how various study characteristics impacted the estimated ERC.

Results:

Sixteen CA (1,356 individuals) and $13\text{\hspace{0.17em}MN}$ studies (2,097 individuals) were found to be eligible for inclusion in a meta-analysis. Studies where benzene was the primary genotoxic exposure and that had adequate assessment of both exposure and outcomes were used for the primary analysis. Estimated slope estimates were an increase of 0.27% CA [(95% CI: 0.08%, 0.47%); based on the results from 4 studies] and 0.27% MN [(95% CI: $-0.23\%$, 0.76%); based on the results from 7 studies] per parts-per-million benzene exposure. We observed considerable between-study heterogeneity for both end points ($I^2>90\%$).

Discussion:

Our study provides a systematic, transparent, and quantitative summary of the literature describing the strong association between benzene exposure and accepted markers of genotoxicity in humans. The derived consensus slope can be used as a best estimate of the quantitative relationship between real-life benzene exposure and genetic damage in future risk assessment. We also quantitate the large between-study heterogeneity that exists in this literature, a factor which is crucial for the interpretation of single-study or consensus slopes. https://doi.org/10.1289/EHP6404

中文翻译：

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职业苯暴露与细胞遗传学损伤生物标志物之间关系的定量Meta分析。

摘要

背景：

在数十项生物监测研究中，主要通过研究（经典）染色体畸变（CAs）或微核（MN）作为DNA损伤的标志物，研究了苯的遗传毒性。在队列研究中，两者均被证明可以预测未来的癌症风险，因此可以潜在地用于遗传毒性介导的癌症的风险评估。

目标：

我们试图估计暴露-响应曲线（ERC），并使用所有现有的关于苯暴露对CAs和MN的细胞遗传学影响的定量证据来量化研究之间的异质性。

方法：

我们进行了系统的文献综述，并使用荟萃分析总结了足够质量的所有可用数据。我们评估了研究之间斜率估算的异质性，并进行了其他敏感性分析，以评估各种研究特征如何影响估算的ERC。

结果：

十六个CA（1,356个人）和 $13\text{\hspace{0.17em}MN}$研究（2,097名个体）被发现符合纳入荟萃分析的条件。苯是主要的遗传毒性暴露，并且对暴露和结果均进行了充分评估的研究被用于主要分析。估计的斜率估计值增加了0.27％CA [（95％CI：0.08％，0.47％）；根据4项研究的结果]和0.27％MN [（95％CI：$-0.23％$，0.76％）；（基于7项研究的结果）。我们观察到两个端点之间的研究之间存在相当大的异质性（${\mathrm{一世}}^2>90％$）。

讨论：

我们的研究提供了系统，透明和定量的文献综述，这些文献描述了苯暴露与人类遗传毒性的可接受标记之间的强烈关联。得出的共识斜率可以用作未来风险评估中真实苯暴露与遗传损害之间定量关系的最佳估计。我们还对文献中存在的大量研究间异质性进行了量化，这对于解释单一研究或共识坡度至关重要。https://doi.org/10.1289/EHP6404