Nilsson R
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Ecotoxicol Environ Saf. 1996 Jun;34(1):2-17. doi: 10.1006/eesa.1996.0040.
It is biologically plausible that environmental tobacco smoke (ETS) has a contributory role in the induction of lung cancer in nonsmoking individuals. However, recent findings have strengthened previous assumptions that a major part of the observed increase in lung cancer risk reported from epidemiological studies on ETS-exposed nonsmokers can be related to misclassification of smoking status and inappropriate selection of controls as well as to certain confounding factors related to life-style, and possibly also to hereditary disposition. Dose-response extrapolation-supported by a more solid database for active smokers-reflects a possible increase in lung cancer that appears to be more than one order of magnitude lower than indicated by the epidemiological studies that have been used to support regulatory action in the United States. The epidemiological studies on ETS conducted so far lack the required sensitivity to confirm increases in risk of such low magnitudes. Self-reported information on exposure to tobacco smoke has been found to be unreliable, and data from interviews with proxy respondents even more so. In addition, determination of cotinine to establish smoking status is inadequate for use in this context, i.e., to assure that misclassification in the range 5-10% does not occur; due to genetically based differences in the rate of nicotine metabolism, some active smokers will not be detected. Further, due the short half-life of cotinine in the organism, a self-reported nonsmoker may, in principle, have been a lifelong heavy smoker until just before the sampling takes place. For some of the major studies, preferential inclusion of disease-prone individuals of very low socioeconomic status among cases seems to have been present to a varying extent. Due to inclusion of this group, life-style and hereditary disposition may result in a disproportionally large impact on the recorded overall lung cancer rate. Further, a possible major confounder causing inflated risk estimates, and that was not controlled for, is apparently a high intake of saturated fat, which to a varying extent is coupled to inadequate intake of anticarcinogens present in certain foods of plant origin. The one-sided preoccupation with ETS as a causative factor of lung cancer in nonsmokers may seriously hinder the elucidation of the multifactorial etiology of these tumors.
从生物学角度来看，环境烟草烟雾（ETS）在非吸烟个体患肺癌过程中起促成作用是有道理的。然而，最近的研究结果强化了之前的假设，即对接触ETS的非吸烟者进行流行病学研究报告的肺癌风险增加，很大一部分可能与吸烟状况的错误分类、对照的不当选择以及某些与生活方式相关的混杂因素有关，也可能与遗传易感性有关。由更可靠的主动吸烟者数据库支持的剂量反应推断表明，肺癌可能的增加幅度似乎比用于支持美国监管行动的流行病学研究所表明的低一个多数量级。迄今为止进行的关于ETS的流行病学研究缺乏确认如此低幅度风险增加所需的敏感性。已发现自我报告的接触烟草烟雾信息不可靠，来自代理受访者访谈的数据更是如此。此外，在这种情况下，用可替宁测定吸烟状况并不足以确保不发生5% - 10%范围内的错误分类；由于基于遗传的尼古丁代谢率差异，一些主动吸烟者可能未被检测到。此外，由于可替宁在生物体内的半衰期短，原则上，一个自我报告的非吸烟者在采样前可能一直是终生重度吸烟者。对于一些主要研究，在病例中似乎不同程度地存在优先纳入社会经济地位极低的易患疾病个体的情况。由于纳入了这一群体，生活方式和遗传易感性可能对记录的总体肺癌发病率产生不成比例的重大影响。此外，一个可能导致风险估计值虚高且未得到控制的主要混杂因素显然是饱和脂肪的高摄入量，在不同程度上，这与某些植物性食物中存在的抗癌物质摄入不足有关。片面地将ETS视为非吸烟者患肺癌的致病因素可能会严重阻碍对这些肿瘤多因素病因的阐明。
