Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, Maryland, USA.
Environ Health Perspect. 2023 Aug;131(8):87002. doi: 10.1289/EHP11980. Epub 2023 Aug 7.
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, , 5-9, 10-19, and 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 [; 95% confidence interval (CI): 1.47, 7.10], followed by a plateau/decline among the heavily exposed (; 95% CI: 0.85, 4.04). Patterns of risk by cumulative REC exposure varied across four exposure time windows (), with ORs increasing for exposures accrued primarily 10-19 y prior to death (). Results provided little support for a waning of risk among workers whose exposures ceased for 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.
矿工柴油机排气研究（DEMS）是国际癌症研究机构（IARC）重新将柴油机排气归类为 I 类致癌物质以及随后进行风险评估的重要贡献者。我们将 DEMS 队列随访延长了 18 年，并将嵌套病例对照研究扩展到包括所有新确诊的肺癌死亡病例和匹配对照（DEMS II），这几乎使肺癌死亡病例的数量增加了一倍。
我们的目的是描述暴露-反应关系，重点关注暴露时间和暴露停止的影响。
我们对 8 家非煤矿中的 12315 名工人进行了一项肺癌病例对照研究（376 例肺癌死亡，718 例对照）。对照者是在病例死亡时仍存活的工人中选择的，按矿山、性别、种族/民族和出生年份（在 5 年内）进行个体匹配。基于广泛的历史暴露评估，我们为每个队列成员估计了可吸入元素碳（REC），这是柴油机暴露的指标。通过条件回归分析，控制吸烟和其他混杂因素，估计了比值比（OR）。为了评估暴露时间窗口，我们评估了四个预先选定的暴露时间窗口内累积 REC 的联合 OR 模式，分别为：，，，以及 y 前死亡/参考日期。我们还评估了累积暴露在时间窗口之间的相互作用，分别以加性和乘法形式进行联合关联。
随着 15 年滞后累积暴露的增加，OR 增加，风险最高增加三倍，暴露为 [; 95%置信区间（CI）：1.47，7.10]，随后在重度暴露者中呈平台/下降趋势（; 95% CI：0.85，4.04）。根据累积 REC 暴露的风险模式因四个暴露时间窗口而异（），主要发生在死亡前 10-19 年的暴露（）的 OR 增加。结果几乎没有为接触停止 y 以上的工人的风险衰减提供支持。
DEMS II 的发现为柴油机排气与肺癌死亡率之间的暴露-反应关系提供了深入了解。在死亡前 10-19 年的时间窗口内发生的暴露的明显影响，在暴露停止 20 年或更长时间后持续存在的风险，以及在暴露程度最高的人群中风险的平台/下降，为柴油机诱导致癌机制的进一步研究提供了方向，除了对监管机构评估柴油机排气的风险具有重要意义外。https://doi.org/10.1289/EHP11980.
