矿工柴油排放调查（Diesel Exhaust in Miners Study, DEMS）对国际癌症研究机构对柴油排放的重新分类为一类致癌物质以及随后的风险评估做出了重要贡献。我们将DEMS队列的随访延长了18年，并扩大了嵌套病例对照研究，包括所有新发现的肺癌死亡和配对对照（DEMS II），几乎使肺癌死亡人数增加了一倍。我们的目的是表征暴露-反应关系，重点关注暴露时机和暴露终止的影响。我们在8000例非金属矿业工人中进行了肺癌病例对照研究（376例肺癌死亡，718例对照）。对照组是从病例死亡时还存活的工人中选择的，与矿山、性别、种族/民族和出生年份（在5年内）匹配。基于广泛的历史暴露评估，我们估计了每位队列成员的可吸入元素碳（REC），即柴油暴露指数。通过条件回归分析，控制吸烟和其他混杂因素，计算出了比值比（OR）。为了评估暴露时间窗口，我们评估了每个预选暴露时间窗口内累积REC的联合OR模式，分别为<5年、5-9年、10-19年和≥20年前到死亡/参考日期，并评估了各时间窗口内累积暴露的交互作用，采用加法和乘法模式进行联合分析。OR随着15年滞后的累积暴露增加而增加，暴露约为950μg/m3-y至<1,700μg/m3-y时风险增至三倍左右[OR=3.23；95%置信区间（CI）：1.47，7.10]，然后在重度暴露人群中达到一个稳定/下降的水平（OR=1.85；95% CI：0.85，4.04）。累积REC各暴露时间窗口下的风险模式有所不同（p<0.001），暴露主要在死亡前10-19年时增加（ptrend<0.001）。结果很少支持曾暴露停止≥20年后风险的减退。DEMS II 结果揭示了柴油排放与肺癌死亡的暴露-反应关系。暴露窗口发生在死亡前10-19年内的显著效应，暴露停止后20年以上仍有持续风险以及在最高暴露者中风险平稳/下降的情况，为研究柴油致癌机制提供了方向，并对监管机构评估柴油排放风险具有重要意义。

The Diesel Exhaust in Miners Study (DEMS) was an important contributor to the International Agency for Research on Cancer reclassification of diesel exhaust as a Group I carcinogen and subsequent risk assessment. We extended the DEMS cohort follow-up by 18 y and the nested case-control study to include all newly identified lung cancer deaths and matched controls (DEMS II), nearly doubling the number of lung cancer deaths.Our purpose was to characterize the exposure-response relationship with a focus on the effects of timing of exposure and exposure cessation.We conducted a case-control study of lung cancer nested in a cohort of 12,315 workers in eight nonmetal mines (376 lung cancer deaths, 718 controls). Controls were selected from workers who were alive when the case died, individually matched on mine, sex, race/ethnicity, and birth year (within 5 y). Based on an extensive historical exposure assessment, we estimated respirable elemental carbon (REC), an index of diesel exposure, for each cohort member. Odds ratios (ORs) were estimated by conditional regression analyses controlling for smoking and other confounders. To evaluate time windows of exposure, we evaluated the joint OR patterns for cumulative REC within each of four preselected exposure time windows, <5, 5-9, 10-19, and ≥20 y prior to death/reference date, and we evaluated the interaction of cumulative exposure across time windows under additive and multiplicative forms for the joint association.ORs increased with increasing 15-y lagged cumulative exposure, peaking with a tripling of risk for exposures of ∼950 to<1,700 μg/m3-y [OR=3.23; 95% confidence interval (CI): 1.47, 7.10], followed by a plateau/decline among the heavily exposed (OR=1.85; 95% CI: 0.85, 4.04). Patterns of risk by cumulative REC exposure varied across four exposure time windows (phomogeneity<0.001), with ORs increasing for exposures accrued primarily 10-19 y prior to death (ptrend<0.001). Results provided little support for a waning of risk among workers whose exposures ceased for ≥20 y.DEMS II findings provide insight into the exposure-response relationship between diesel exhaust and lung cancer mortality. The pronounced effect of exposures occurring in the window 10-19 y prior to death, the sustained risk 20 or more years after exposure ceases, and the plateau/decline in risk among the most heavily exposed provide direction for future research on the mechanism of diesel-induced carcinogenesis in addition to having important implications for the assessment of risk from diesel exhaust by regulatory agencies. https://doi.org/10.1289/EHP11980.