Erren Thomas C, Glende Christine B, Morfeld Peter, Piekarski Claus
Institute and Policlinic for Occupational and Social Medicine, School of Medicine and Dentistry, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Lindenthal, Germany.
Int Arch Occup Environ Health. 2009 Aug;82(8):997-1004. doi: 10.1007/s00420-008-0387-0. Epub 2008 Dec 6.
This report investigates epidemiologically whether exposure to silica is associated with lung cancer risks in individuals without silicosis.
We searched the PubMed reference data base from 1966 through 1/2007 for reports of lung cancer in silica-exposed persons without and with silicosis. To explore heterogeneity between studies, a multi-stage strategy was employed. First, fixed-effect summaries (FES) and corresponding 95% confidence intervals (CI) for various combinations of studies were calculated, weighting individual results by their precision. The homogeneity of the contributing results was examined using chi(2) statistics. Where there was evidence of substantial heterogeneity, the CI around the FES was increased to take account of the between-study variability. Random-effect summaries and their CI for identical combinations of studies were also computed. Meta regression was used to explore interactions with covariates. To draw comparisons, parallel analyses were performed for non-silicotics and for silicotics.
The persistence of a significant link between silicosis and lung cancer since the characterisation in 1997 of silica as a human carcinogen [our estimates of lung cancer relative risks (RR) exceeded unity in each of 38 eligible studies of silicotics published until 1/2007, averaging 2.1 in analyses based on both fixed and random effect models (95% CI = (2.0-2.3) and (1.9-2.3), respectively)] does not resolve our study question, namely whether exposure to silica levels below those required to induce silicosis are carcinogenic. Importantly, our detailed examination of 11 studies of lung cancer in silica-exposed individuals without silicosis included only three with data allowing adjustment for smoking habits. They yielded a pooled RR estimate of 1.0 [95% CI = (0.8-1.3)]. The other eight studies, with no adjustment for smoking habits, suggested a marginally elevated risk of lung cancer [RR = 1.2; 95% CI (1.1-1.4)], but with significant heterogeneity between studies (P approximately 0.05).
Necessary further research should concentrate on silica exposures both above and below those that induce silicosis, so that the shape of the exposure-response relationship may be identified, with adjustments for likely confounding factors including silicosis. Time-dependent information on silicosis and on silica dust is required as well as the application of methods like G-estimation to answer the important public health question: Is silicosis a necessary condition for the elevation of silica-associated lung cancer risks?
本报告从流行病学角度调查了在无矽肺的个体中，接触二氧化硅是否与肺癌风险相关。
我们检索了1966年至2007年1月期间的PubMed参考文献数据库，以查找有关接触二氧化硅且无矽肺和有矽肺的人群中肺癌的报告。为了探究研究之间的异质性，采用了多阶段策略。首先，计算了各项研究不同组合的固定效应汇总值（FES）及其相应的95%置信区间（CI），根据各项结果的精度对其进行加权。使用卡方统计量检验各贡献结果的同质性。若有证据表明存在显著异质性，则扩大FES周围的CI以考虑研究间的变异性。还计算了相同研究组合的随机效应汇总值及其CI。采用Meta回归来探究与协变量的相互作用。为了进行比较，对无矽肺者和有矽肺者进行了平行分析。
自1997年将二氧化硅确定为人类致癌物以来，矽肺与肺癌之间一直存在显著关联[在截至2007年1月发表的38项关于有矽肺者的合格研究中，我们对肺癌相对风险（RR）的估计在每项研究中均超过1，基于固定效应模型和随机效应模型的分析中，平均RR分别为2.1（95%CI=(2.0 - 2.3)）和（1.9 - 2.3）]，但这并未解决我们的研究问题，即接触低于诱发矽肺所需水平的二氧化硅是否具有致癌性。重要的是，我们对11项关于接触二氧化硅但无矽肺的个体的肺癌研究进行的详细审查中，只有3项研究的数据允许对吸烟习惯进行调整。它们得出的合并RR估计值为1.0[95%CI=(0.8 - 1.3)]。其他8项未对吸烟习惯进行调整的研究表明肺癌风险略有升高[RR = 1.2；95%CI(1.1 - 1.4)]，但研究之间存在显著异质性（P约为0.05）。
必要的进一步研究应集中在诱发矽肺水平之上和之下的二氧化硅暴露情况，以便能够确定暴露 - 反应关系的形式，并对包括矽肺在内的可能混杂因素进行调整。需要有关矽肺和二氧化硅粉尘的时间依赖性信息，以及应用G - 估计等方法来回答这个重要的公共卫生问题：矽肺是否是二氧化硅相关肺癌风险升高的必要条件？
