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Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

Environmental health perspectives(2024)SCI 1区

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Abstract
BACKGROUND:While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents.OBJECTIVES:We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking.METHODS:In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI).RESULTS:All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8).DISCUSSION:Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.
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Asbestos exposure,Exposure Assessment,Occupational carcinogens
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要点】:本研究通过汇总分析探究了职业暴露于五种肺癌致癌物的成对联合效应对肺癌风险的影响,发现多种致癌物的共同暴露通常导致高于单独暴露的风险。

方法】:研究采用了一个定量的职业暴露矩阵(SYN-JEM)对14个中心的16,901例肺癌病例和20,965名对照的职业暴露进行分类,并使用逻辑回归模型计算比值比(ORs)和95%置信区间(CIs)。

实验】:在SYNERGY项目中,通过职业暴露矩阵对参与者进行分类,评估了成对致癌物的联合效应,使用乘法尺度和加法尺度进行评估,加法尺度通过计算相对交互超额风险(RERI)来实现。结果显示,男性的所有成对联合效应均与肺癌风险增加相关,而女性的小细胞肺癌与PAH/硅和石棉/硅的共同暴露显著相关,其中PAH/硅的共同暴露显示出协同效应。