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A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer

机译：六价铬与肺癌关系中的阈值和其他非线性关系的搜索

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The exposure-response relationship for airborne hexavalent chromium exposure and lung cancer mortality is well described by a linear relative rate model. However, categorical analyses have been interpreted to suggest the presence of a threshold. This study investigates nonlinear features of the exposure response in a cohort of 2,357 chemical workers with 122 lung cancer deaths. In Poisson regression, a simple model representing a two-step carcinogenesis process was evaluated. In a one-stage context, fractional polynomials were investigated. Cumulative exposure dose metrics were examined corresponding to cumulative exposure thresholds, exposure intensity (concentration) thresholds, dose-rate effects, and declining burden of accumulated effect on future risk. A simple two-stage model of carcinogenesis provided no improvement in fit. The best-fitting one-stage models used simple cumulative exposure with no threshold for exposure intensity and had sufficient power to rule out thresholds as large as 30 μg/m~3 CrO_3 (16 μg/m~3 as Cr~(+6)) (one-sided 95% confidence limit, likelihood ratio test). Slightly better-fitting models were observed with cumulative exposure thresholds of 0.03 and 0.5 mg-yr/m~3 (as CrO_3) with and without an exposure-race interaction term, respectively. With the best model, cumulative exposure thresholds as large as 0.4 mg-yr/m~3 CrO_3 were excluded (two-sided upper 95% confidence limit, likelihood ratio test). A small departure from dose-rate linearity was observed, corresponding to (intensity)~(0.8) but was not statistically significant. Models in which risk-inducing damage burdens declined over time, based on half-lives ranging from 0.1 to 40 years, fit less well than assuming a constant burden. A half-life of 8 years or less was excluded (one-sided 95% confidence limit). Examination of nonlinear features of the hexavalent chromium-lung cancer exposure response in a population used in a recent risk assessment supports using the traditional (lagged) cumulative exposure paradigm: no intensity (concentration) threshold, linearity in intensity, and constant increment in risk following exposure.
机译：线性相对比率模型很好地描述了空气中六价铬暴露与肺癌死亡率的暴露-反应关系。但是，分类分析已被解释为建议存在阈值。这项研究调查了2357名化学工作者与122名肺癌死亡的队列研究中暴露反应的非线性特征。在泊松回归中，评估了代表两步致癌过程的简单模型。在一个阶段的上下文中，研究了分数多项式。检查了累积暴露剂量指标，这些度量分别对应于累积暴露阈值，暴露强度（浓度）阈值，剂量率效应以及对未来风险的累积效应下降的负担。一个简单的两阶段癌变模型不能改善健康状况。最适合的一阶段模型使用简单的累积暴露量，没有暴露强度阈值，并且具有足够的功率来排除高达30μg/ m〜3 CrO_3（16μg/ m〜3为Cr〜（+6）的阈值）（单边95％置信限，似然比检验）。观察到拟合较好的模型，累积暴露阈值分别为0.03和0.5 mg-yr / m〜3（以CrO_3计），有和没有暴露-种族相互作用项。在最佳模型中，排除了0.4 mg-yr / m〜3 CrO_3的累积暴露阈值（双面置信度上限为95％，似然比检验）。观察到剂量率线性度略有偏离，对应于（强度）〜（0.8），但无统计学意义。基于0.1到40年的半衰期，导致风险的损害负担随着时间的推移而下降的模型，其拟合效果不如假定恒定的负担。半衰期不超过8年（单侧置信度为95％）。在最近的风险评估中，对人群中六价铬-肺癌癌暴露反应的非线性特征的研究支持使用传统的（滞后）累积暴露范式：无强度（浓度）阈值，强度线性和风险跟随性不断增加接触。

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