Puntoni R, Toninelli F, Zhankui L, Bonassi S
Department of Environmental Epidemiology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Carcinogenesis. 1995 Jul;16(7):1465-71. doi: 10.1093/carcin/16.7.1465.
The existence of a dose-related increase of lung cancer risk in cigarette smokers has been indisputably established. This finding, however, is not confirmed at low doses (< 5 cigarettes/day), there still being a lack of epidemiological data. The use of mathematical models of carcinogenesis to extrapolate from higher doses allows estimation of the risk for very light smokers. The present study has been designed to compare a set of mathematical models, i.e. one-hit, two-stage, multi-stage, logit, probit, and Weibull, in extrapolating relative risks at low doses from the data of nine large cohort studies on cigarette smokers reported in the IARC Scientific Monograph on tobacco smoking. All models evaluated, apart from the one-hit, achieved a good fit, with the proportion of explained variance ranging between 61% and 67%. The relative risk estimates for passive smokers from the most updated epidemiological studies were taken into account to evaluate, on the basis of these models, the corresponding exposure in terms of 'cigarette equivalent' smoked. These values ranged from 0.21 to 0.43 cigarettes/day for the two-stage and multi-stage model, while probit, logit and Weibull models, yielded estimates one or even two orders of magnitude lower. The authors emphasize the substantial agreement between the estimates of 'cigarette equivalent' based on the application of two-stage and multi-stage models to the epidemiological evidence on the effect of passive smoking and to the data based on the comparison of tobacco metabolites in active and passive smokers.
吸烟人群中肺癌风险存在剂量相关增加这一现象已得到确凿证实。然而，在低剂量（<5支/天）情况下这一发现并未得到证实，目前仍缺乏流行病学数据。利用癌症发生的数学模型从高剂量进行外推，可以估算轻度吸烟者的风险。本研究旨在比较一组数学模型，即单 hit 模型、两阶段模型、多阶段模型、logit 模型、probit 模型和 Weibull 模型，以便根据国际癌症研究机构（IARC）关于吸烟的科学专论中报道的九项大型吸烟者队列研究的数据，外推低剂量时的相对风险。除单 hit 模型外，所有评估的模型拟合效果都很好，可解释方差比例在61%至67%之间。考虑到最新流行病学研究中对被动吸烟者相对风险的估计，基于这些模型评估了以“香烟当量”表示的相应暴露量。两阶段模型和多阶段模型得出的这些值为0.21至0.43支/天，而probit模型、logit模型和Weibull模型得出的估计值低一个甚至两个数量级。作者强调，基于两阶段模型和多阶段模型应用于被动吸烟影响的流行病学证据以及基于主动吸烟者和被动吸烟者烟草代谢物比较的数据得出的“香烟当量”估计值之间存在实质性一致性。
