Carta P, Aru G, Manca P
Institute of Occupational Medicine, University of Cagliari, Via S Georgio 12, 09124 Cagliari, Italy.
Occup Environ Med. 2001 Dec;58(12):786-93. doi: 10.1136/oem.58.12.786.
To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997.
Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society's criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates.
The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox's proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates.
The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors-such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines-rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself.
为评估二氧化硅、矽肺与肺癌之间的关联,我们对724例于1964年至1970年间首次经标准胸部X光片诊断为矽肺的患者进行了队列研究,直至1997年12月31日分析其死亡率。
该队列中的每位成员均有吸烟及详细职业史,以及可吸入二氧化硅粉尘和氡子体的估计终生暴露量。两名独立阅片者依据国际劳工组织(ILO)的12分制标准对标准X光片进行盲法分类。665例患者进行了符合美国胸科学会标准的肺功能测试。选定死因的标准化死亡比(SMR)基于撒丁岛地区特定年龄的死亡率。
所有原因导致的死亡率显著高于预期(SMR 1.35,95%置信区间(95%CI)1.24至1.46),主要归因于肺结核(SMR 22.0)和非恶性慢性呼吸道疾病(NMCRD)(SMR 6.03)。所有癌症死亡人数均在预期范围内(SMR 0.93;95%CI 0.76至1.14)。肺癌的SMR为1.37(95%CI 0.98至1.91,观察到34例),自首次诊断矽肺起20年潜伏期后增至1.65(95%CI 0.98至2.77)。尽管NMCRD的死亡率与放射学矽肺的严重程度及二氧化硅累积暴露程度密切相关,但肺癌的SMR仅在滞后20年间隔后才与ILO类别及二氧化硅粉尘累积暴露呈弱相关。在先前受雇于地下金属矿且空气中氡子体浓度相对较高的矽肺患者中,以及在首次诊断矽肺时存在气流阻塞的曾经吸烟者中,发现肺癌死亡显著超额(SMR 2.35)(SMR 3.29)。通过整个队列中的Cox比例风险模型及一项巢式病例对照研究(34例肺癌病例和136例匹配对照)评估与暴露相关的肺癌死亡率。两项多变量分析均未显示与二氧化硅累积暴露或矽肺严重程度有任何显著关联,但证实肺癌死亡率与相对高的氡暴露、吸烟及气流阻塞作为显著协变量之间存在关联。
研究结果表明,该矽肺患者队列中肺癌死亡率的轻微升高与其他风险因素显著相关,如吸烟、气流阻塞以及地下矿中估计的氡子体暴露,而非与放射学矽肺的严重程度或结晶二氧化硅粉尘的累积暴露本身相关。