Indirect validation of a retrospective method of exposure assessment used in a nested case-control study of lung cancer and silica exposure.

Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed.     

Exposure to crystalline silica, silicosis, and lung disease other than cancer in diatomaceous earth industry workers: a quantitative risk assessment

Objectives: To estimate excess lifetime risk of (a) mortality from lung disease other than cancer (LDOC), and, (b) onset of radiographic silicosis, arising from occupational exposure to respirable crystalline silica dust.

Methods: Data from a cohort of California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly as cristobalite) were reanalyzed with Poisson regression methods with internal and external adjustments for potential confounding by calendar time, age, smoking, Hispanic ethnicity, and time since first observation. Model fit was evaluated by comparing deviances and fitting cubic spline models. Lifetime risks of death from LDOC and radiographic silicosis were estimated up to age 85 with an actuarial approach accounting for competing causes of death.

Results: For deaths due to LDOC, a linear relative rate model gave the best fit in Poisson regression analyses. At the mean cumulative exposure of LDOC cases to silica, after adjustment for smoking, the estimated rate ratio was 4.2 (p<0.0001); at the maximum cumulative exposure of cases, the rate ratio was 18.4. The excess lifetime risk for white men exposed to respirable cristobalite dust for 45 years at the current permissible exposure limit (PEL; about 0.05 mg/m³) of the Occupational Safety and Health Administration was 54/1000 (95% confidence interval (95% CI) 17 to 150). For 70 incident cases of radiographic silicosis largely manifest before the end of employment, the best fit was also the linear relative rate model, predicting a rate ratio of 25.6 for silicosis at the mean cumulative exposure of the cases (p<0.0001). The excess lifetime risk for silicosis at the current PEL was 75/1000.

Conclusion: Current occupational health standards for crystalline silica permit risks of lung disease other than cancer far in excess of what is usually considered acceptable by the Occupational Safety and Health Administration (a lifetime risk of less than one in a thousand deaths).

     

Silicosis and lung cancer among Chinese granite workers.

Of the 184 cases of silicosis registered between 1 January 1970 and 31 December 1984 in Singapore, all the relevant information was available for 159, which were linked to the population-based National Cancer Register for lung cancer. Nine cases of lung cancer were found. The standardized incidence ratio (SIR) was computed with the age- and calendar-specific incidence of lung cancer rates of Chinese males in Singapore as a basis. Excess risk of lung cancer was found (SIR 2.01, 95% confidence interval 0.92-3.81). Adjustment for smoking showed that it alone could not account for the excess lung cancer risk. There was an increasing, but not significant, trend with increasing severity of silicosis and exposure duration. The results suggest that the severity of silicosis and possibly exposure to free silica may have contributed to the excess of lung cancer among the cases of silicosis studied.     

二氧化硅,矽肺与肺癌的关系

通过耐火材料等四个行业的接尘人员中肺癌死亡回顾性队列调查,发现接尘人员中肺癌危险性明显高于非尘毒暴露组,而且肺癌标化死亡率随含硅量及接触浓度变化呈现出平行的趋势。矽肺合并肺癌多为早期矽肺,肺癌病变多分布在肺上叶,病理形态鳞癌较多。肺癌发生晚于矽肺。吸烟和矽肺同时存在时,有必要注意协同作用。     

Mortality from lung cancer among Sardinian patients with silicosis

The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the Sardinia region of Italy, was followed up through to 31 December 1987. Smoking, occupational history, chest x ray films, and data on lung function were available from clinical records for each member of the cohort. The overall cohort accounted for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected causes of death (International Classification of Diseases (ICD) eighth revision) were based on the age specific regional death rates for each calendar year. An excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic obstructive lung disease, silicosis, and tuberculosis with an upward trend of the SMR with increasing severity of the International Labour Office (ILO) radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29, 95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15 year latency but the SMR never reached statistical significance. No correlation was found between lung cancer and severity of the radiological category, the type of silica (coal or metalliferous mines, quarries etc), or the degree of exposure to silica dust. A significant excess of deaths from lung cancer was found among heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A nested case-control study was planned to investigate whether the association between lung cancer and airway obstruction was due to confounding by smoking. No association was found with the ILO categories of silicosis or the estimated cumulative exposure to silica. The risk estimate for lung cancer by airflow obstruction after adjusting by cigarette consumption was 2.86 for a mild impairment and 7.23 for a severe obstruction. The results do not show any clear association between exposure to silica, severity of silicosis, and mortality from lung cancer. Other environmental or individual factors may act as confounders in the association between silicosis and lung cancer. Among them, attention should be given to chronic airways obstruction as an independent risk factor for lung cancer in patients with silicosis.     

Mortality from lung cancer among Sardinian patients with silicosis.

The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the Sardinia region of Italy, was followed up through to 31 December 1987. Smoking, occupational history, chest x ray films, and data on lung function were available from clinical records for each member of the cohort. The overall cohort accounted for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected causes of death (International Classification of Diseases (ICD) eighth revision) were based on the age specific regional death rates for each calendar year. An excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic obstructive lung disease, silicosis, and tuberculosis with an upward trend of the SMR with increasing severity of the International Labour Office (ILO) radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29, 95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15 year latency but the SMR never reached statistical significance. No correlation was found between lung cancer and severity of the radiological category, the type of silica (coal or metalliferous mines, quarries etc), or the degree of exposure to silica dust. A significant excess of deaths from lung cancer was found among heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A nested case-control study was planned to investigate whether the association between lung cancer and airway obstruction was due to confounding by smoking. No association was found with the ILO categories of silicosis or the estimated cumulative exposure to silica. The risk estimate for lung cancer by airflow obstruction after adjusting by cigarette consumption was 2.86 for a mild impairment and 7.23 for a severe obstruction. The results do not show any clear association between exposure to silica, severity of silicosis, and mortality from lung cancer. Other environmental or individual factors may act as confounders in the association between silicosis and lung cancer. Among them, attention should be given to chronic airways obstruction as an independent risk factor for lung cancer in patients with silicosis.     

Lung cancer mortality among a cohort of men in a silicotic register

To examine any association between silicosis and lung cancer, the clinic records of a cohort of 1502 silicotic workers diagnosed after 1981 were reviewed. All of the essential data, including occupational exposure, smoking habits, radiographic extent of silicosis, and vital status of each subject, were noted. The standardized mortality ratio for various causes of death was calculated. Thirty-three patients died from lung cancer, giving a standardized mortality ratio of 1.94 (95% confidence interval, 1.35 to 2.70). However, smoking accounted for most of the excess of lung cancer deaths among the silicotic workers in the cohort, and no consistent relationship between lung cancer mortality risk and either duration of exposure to silica dust or severity of silicosis was observed. There is no conclusive evidence in our data to support the hypothesis that lung cancer may be associated with silicosis.     

Silicosis and smoking strongly increase lung cancer risk in silica-exposed workers

It remains controversial whether silica is a human lung carcinogen. In this study, we estimated the relative risks of lung cancer due to silica and silicosis by meta-analysis. We collected papers published from 1966-2001 which epidemiologically reported on the relationship between silica/silicosis and lung cancer. We removed papers which did not exclude the effects of asbestos and radioactive materials including radon. We selected the most recent one if some papers were based on the same cohort. Based on the selected papers, we summarized the lung cancer risks from silica, silicosis and non-silicosis with exposure to silica, by meta-analysis using a random effects model. The pooled relative risks were 1.32 (95% confidence interval (CI), 1.23-1.41) for silica, 2.37 (95% CI, 1.98-2.84) for silicosis and 0.96 (95% CI, 0.81-1.15) for non-silicosis with exposure to silica. Since some papers on silica did not exclude silicosis, the risk due to silica itself may be smaller than 1.32. It was less possible that silica exposure directly increases lung cancer risk. On the other hand, the relative risk, 2.37 for silicosis suggested that silicosis increases lung cancer risk. Meta-analysis also revealed that cigarette smoking strongly increased the lung cancer risk in silicotic patients (relative risk, 4.47; 95% CI, 3.17-6.30). Thus, the present study suggested the great importance of preventing silicosis and smoking cessation in reducing lung cancer incidence in silica-exposed workers.     

One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure

BACKGROUND: Evidence in recent years indicates that silica causes lung cancer, and probably renal disease, in addition to its well-known relationship to silicosis. There is also suggestive evidence that silica can cause arthritis and other auto-immune diseases. Silica has, therefore, joined a handful of other toxic exposures such as tobacco smoke, dioxin, and asbestos which cause multiple serious diseases. METHODS: The available exposure-response data for silica and silicosis, lung cancer, and renal disease are reviewed. We compare the corresponding excess risks (or absolute risks in the case of silicosis) of death or disease incidence by age 75 for these three diseases, subsequent to a lifetime (45 years) of exposure to silica at current US standard (0.1 mg/m(3) respirable crystalline silica). RESULTS: The absolute risk of silicosis, as defined by small opacities greater than or equal to ILO classification 1/1 on an X-ray, ranges from 47% to 77% in three cohort studies with adequate follow-up after employment. The absolute risk of death from silicosis is estimated at 1.9% (0.8%-2.9%), based on a pooled analysis of six cohort studies. The excess risk of lung cancer death, assuming US male background rates, is 1.7% (0.2%-3.6%), based on a pooled analysis of ten cohort studies. The excess risk of end-stage renal disease (assuming male background rates) is 5.1% (2.2%-7.3%), based on a single cohort. The excess risk of death from renal disease is estimated to be 1.8% (0.8%-9.7%), based on a pooled analysis of three cohorts. CONCLUSIONS: Keeping in mind that the usual OSHA acceptable excess risk of serious disease or death for workers is 0.1%, it is clear that the current standard is far from sufficiently protective of workers' health. Perhaps surprisingly, kidney disease emerges as perhaps a higher risk than either mortality from silicosis or lung cancer, although the data are based on fewer studies.     

Change of exposure response over time and long-term risk of silicosis among a cohort of Chinese pottery workers

An analysis was conducted on a cohort of Chinese pottery workers to estimate the exposure-response relationship between respirable crystalline silica dust exposure and the incidence of radiographically diagnosed silicosis, and to estimate the long-term risk of developing silicosis until the age of 65. The cohort comprised 3,250 employees with a median follow-up duration of around 37 years. Incident cases of silicosis were identified via silicosis registries (Chinese X-ray stage I, similar to International Labor Organisation classification scheme profusion category 1/1). Individual exposure to respirable crystalline silica dust was estimated based on over 100,000 historical dust measurements. The association between dust exposure, incidence and long-time risk of silicosis was quantified by Poisson regression analysis adjusted for age and smoking. The risk of silicosis depended not only on the cumulative respirable crystalline silica dust exposures, but also on the time-dependent respirable crystalline silica dust exposure pattern (long-term average concentration, highest annual concentration ever experienced and time since first exposure). A long-term "excess" risk of silicosis of approximately 1.5/1,000 was estimated among workers with all annual respirable crystalline silica dust concentration estimates less than 0.1 mg/m(3), using the German measurement strategy. This study indicates the importance of proper consideration of exposure information in risk quantification in epidemiological studies.     

肺癌病因研究中接尘量计算的真实性评价

为评价肺癌病例对照研究中接尘剂量估算方法的真实性,对广西锡矿病因研究对象进行了重新计算。广西锡矿队列发现男性肺癌死者１３０例,配对照６２７例。共７５７人。其中接法工人５７２名,发现各期矽肺共２４３例,根据在斩工业卫生监测资料估算所有接尘工人的累积总粉尘接触量,再计算不同接尘水平下矽肺的发病率。结果显示,随接尘水平上升,矽肺发病率升高,两者存在明显的接触剂量反应关系。完全符合矽肺发病特点。从而间接证     

Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners [published erratum appears in Occup Environ Med 1999 Mar;56(3):215-6]

OBJECTIVES: To investigate the following questions. (1) Is silica dust on its own, without the presence of silicosis, associated with an increased risk of pulmonary tuberculosis (PTB) in workers exposed to silica dust? (2) In the absence of silicosis is the excess risk dose related? (3) What is the predominant chronological sequence between the development of PTB and the development of silicosis after the end of exposure to dust? METHODS: A cohort of 2255 white South African gold miners has been followed up from 1968 to 1971, when they were 45-55 years of age, to 31 December 1995 for the incidence of PTB. During the follow up 1592 (71%) men died. Of these, 1296 (81%) had a necropsy done at the National Centre for Occupational Health (NCOH) to determine the presence of silicosis and PTB. The incidence of PTB in the cohort was studied relative to cumulative exposure to dust and the onset of silicosis. For the miners with necropsy, the incidence for PTB was studied relative to the severity of silicosis found at necropsy. RESULTS: There were 115 subjects who developed PTB. The total person- years of follow up was 39,319. For the whole cohort, the factors associated with increased risk of PTB were cumulative exposure to dust (mg/m3.y) (the adjusted rate ratio (RR) 1.07; (95% confidence interval (95% CI) 1.04 to 1.10)), silicosis diagnosed radiologically (3.96 (2.59 to 6.06)), and tobacco pack-years (1.02 (1.01 to 1.03)). The RR (95% CI) for PTB increased with increasing quartiles of cumulative exposure to dust 1.0, 1.51 (0.78 to 2.91), 2.35 (1.28 to 4.32), and 3.22 (1.75 to 5.90). In miners who did not have radiologically diagnosed silicosis (n = 1934, PTB = 74), the adjusted RR (95% CI) for PTB and cumulative exposure to dust was 1.10 (1.06 to 1.13), and increased with quartiles of cumulative exposure to dust as 1.00, 1.46 (0.70 to 3.03), 2.67 (1.37 to 5.23), and 4.01 (2.04 to 7.88). For the subjects who had a necropsy (n = 1296, PTB = 70), the adjusted RR (95% CI) for PTB increased with the severity of silicosis found at necropsy; 1.0 for no silicosis, 1.88 (0.97 to 3.64) for negligible, 2.69 (1.35 to 5.37) for slight, and 2.30 (1.16 to 4.58) for moderate or marked silicosis. For subjects who had a necropsy and no silicosis (n = 577, PTB = 18), the adjusted RR (95% CI) increased slightly with quartiles of cumulative dust 1.0, 1.11 (0.31 to 4.00), 1.42 (0.43 to 4.72), and 1.38 (0.33 to 5.62). CONCLUSION: Exposure to silica dust is a risk factor for the development of PTB in the absence of silicosis, even after exposure to silica dust ends. The risk of PTB increases with the presence of silicosis, and in miners without radiological silicosis, with quartiles of exposure to dust. The severity of silicosis diagnosed at necropsy was associated with increasing risk of PTB and even < 5 nodules--that is, undetectable radiologically--was associated with an increased risk of PTB. The diagnosis of PTB was on average 7.6 years after the end of exposure to dust, at around 60 years of age. The onset of radiological silicosis preceded the diagnosis of PTB in 90.2% of the cases with PTB who had silicosis. The results have implications for medical surveillance of workers exposed to silica dust after the end of exposure.       

Lung cancer among industrial sand workers exposed to crystalline silica

In 1997, the International Agency for Research on Cancer determined that crystalline silica was a human carcinogen but noted inconsistencies in the epidemiology. There are few exposure-response analyses. The authors examined lung cancer mortality among 4,626 industrial sand workers, estimating exposure via a job-exposure matrix based on 4,269 industrial hygiene samples collected in 1974--1995. The average length of employment was 9 years, and estimated average exposure was 0.05 mg/m(3) (the National Institute of Occupational Safety and Health Recommended Exposure Limit). Results confirmed excess mortality from silicosis/pneumoconioses (standardized mortality ratio = 18.2, 95% confidence interval: 10.6, 29.1; 17 deaths). The lung cancer standardized mortality ratio was 1.60 (95% confidence interval: 1.31, 1.93; 109 deaths). Limited data suggested that smoking might account for 10--20% of the lung cancer excess. Exposure-response analyses by quartile of cumulative exposure (15-year lag) yielded standardized rate ratios of 1.00, 0.78, 1.51, and 1.57 (p for trend = 0.07). Nested case-control analyses after exclusion of short-term workers, who had high overall morality, yielded odds ratios by quartile of cumulative exposure (15-year lag) of 1.00, 1.35, 1.63, and 2.00 (p for trend = 0.08) and odds ratios by quartile of average exposure of 1.00, 0.92, 1.44, and 2.26 (p = 0.005). These data lend support to the labeling by the International Agency for Research on Cancer of silica as a human carcinogen. There are approximately 2 million US workers exposed to silica; 100,000 are exposed to more than 0.1 mg/m(3).     

Lung cancer among silica-exposed workers: the quest for truth between chance and necessity

BACKGROUND: In 1997, IARC upgraded crystalline silica to a Group 1 human carcinogen. However, the IARC report itself acknowledged variations in risk depending on inherent characteristics of the crystalline silica or external factors affecting its biological activity or distribution of its polymorphs. METHODS: We reviewed silica physical and physico-chemical properties and how such properties may affect its interaction with the target cells. Studies of silica, silicosis and lung cancer published from 1997 onwards are then reviewed in the search of any new advances in knowledge about silica carcinogenicity. Finally, other possible confounding factors contributing to inconsistent findings on silica, silicosis, and lung cancer are reviewed. RESULTS: Host factors, physico-chemical characteristics of the surface of silica particles, exposure circumstances, and the mineral ore composition experimentally affect the ability of silica particles of inducing release of reactive oxygen species (ROS) and TNF-alpha by alveolar macrophages, possibly accounting for the great variation in lung cancer risk among dust exposed workers across the individual studies. Most recent epidemiological studies do not consider such complex pattern of modifying factors, and they keep replicating inconsistent findings. The hypothesis of a silicosis-mediated pathway, although more consistent from an epidemiological perspectives, and reassuring in terms of the effectiveness of current standards in preventing lung cancer risk among silica exposed workers, does not seem to explain elevated risks at low silica exposure levels. CONCLUSION: Future studies of lung cancer risk among workers exposed to silica-containing dust should consider measurement of ROS and TNF-alpha release by workplace dust samples as intermediate end-points predicting lung cancer risk better than silica concentration, allowing to more effectively address preventive action.     

Silica exposure, silicosis, and lung cancer: a mortality study of South African gold miners.

The effects of exposure to gold mining dust with a high concentration of free silica and tobacco smoking on mortality from lung cancer was assessed in a sample of 2209 white South African gold miners who started mining exposure during 1936-43, and were selected for a study of respiratory disorders in 1968-71 when they were aged 45-54. The mortality follow up was from 1968-71 to 30 December 1986. The relative risk for the effect of dust cumulated to the start of the follow up period was estimated as 1.023 (95% confidence interval (CI) 1.005-1.042) for a unit of 1000 particle-years. The combined effect of dust and tobacco smoking was better fitted by the multiplicative model than the additive model, suggesting that the two exposures act synergistically. No association between lung cancer and silicosis of the parenchyma or pleura was found, but a positive association existed between silicosis of the hilar glands and lung cancer.     

Non-malignant respiratory diseases and lung cancer among Chinese workers exposed to silica

The objective of this study was to explore whether a medical history for non-malignant respiratory disease contributes to an increased lung cancer risk among workers exposed to silica. We analyzed data from a nested case-control study in 29 dusty workplaces in China. The study population consisted of 316 lung cancer cases and 1356 controls matched to cases by facility type and decade of birth who were alive at the time of diagnosis of the index case and who were identified in a follow-up study of about 68,000 workers. Age at first exposure and cigarette smoking were accounted for in the analysis. Smoking was the main risk factor for both lung cancer and chronic bronchitis. Lung cancer risk showed a modest association with silicosis and with cumulative silica exposure, which did not vary by history of previous pulmonary tuberculosis. Among subjects without a medical history for chronic bronchitis or asthma, lung cancer risk was associated with silicosis (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), and it was increased in each quartile of cumulative silica exposure. However, risk was not elevated in the highest quartile (OR, 1.3, 1.6, 1.8, 1.4). Among subjects with a medical history for chronic bronchitis or asthma, lung cancer risk was associated with neither silicosis (subjects with chronic bronchitis: OR, 0.6; subjects with asthma: OR, 0.4) nor with silica exposure. In this study population, we observed a modest association of both silicosis and cumulative exposure to silica with lung cancer among subjects who were not previously diagnosed with chronic bronchitis or asthma, but not among subjects who had a medical history for either disease. Risk of lung cancer associated with silicosis or cumulative exposure to silica did not vary by previous medical history of pulmonary tuberculosis.     

Silica exposure, silicosis, and lung cancer: a mortality study of South African gold miners.

The effects of exposure to gold mining dust with a high concentration of free silica and tobacco smoking on mortality from lung cancer was assessed in a sample of 2209 white South African gold miners who started mining exposure during 1936-43, and were selected for a study of respiratory disorders in 1968-71 when they were aged 45-54. The mortality follow up was from 1968-71 to 30 December 1986. The relative risk for the effect of dust cumulated to the start of the follow up period was estimated as 1.023 (95% confidence interval (CI) 1.005-1.042) for a unit of 1000 particle-years. The combined effect of dust and tobacco smoking was better fitted by the multiplicative model than the additive model, suggesting that the two exposures act synergistically. No association between lung cancer and silicosis of the parenchyma or pleura was found, but a positive association existed between silicosis of the hilar glands and lung cancer.     

Mortality of a cohort of men in a silicosis register: further evidence of an association with lung cancer

Lung cancer mortality from 1980 to 1986 was studied in a cohort of 1,419 men in a silicosis register who had no previous exposure to asbestos and polyaromatic hydrocarbons. The 28 deaths from lung cancer were statistically in excess of expected (SMR 2.03; 95% CI 1.35-2.93). Excess risks of lung cancer were found in both underground workers (SMR 3.41; 95% CI 1.10-7.97; based on 5 deaths) and surface workers (SMR 1.87, 95% CI 1.18-2.81; based on 23 deaths). All lung cancer deaths were smokers. There was an increase in SMRs with longer latency periods and years of exposure, with the greatest risk found in those who had worked for 30 or more years after more than 30 years since first exposed (SMR 3.07, based on 16 deaths). The risk for lung cancer was higher in those with tuberculosis (SMR 2.52; 95% CI 1.52-3.94) and showed an increasing trend with severity of silicosis, from category 1 to 3 and from category A to C, with highest risk in those with tuberculosis and category 3 (SMR 4.44 based on 3 deaths) or tuberculosis and category C (SMR 7.63 based on 7 deaths). Most of the excess lung cancer risk in silicotics is due to smoking, but a synergistic effect between smoking and silica/silicosis on the risk of lung cancer is also likely. In particular, a possible role of silicosis and tuberculosis as the fibrotic seedbed for malignant growth in the lung is strongly supported.     

矽肺对肺癌及总死亡影响的回顾性队列研究

目的 利用香港矽肺患者队列的资料进行分析,探讨矽尘、矽肺与肺癌的关系.方法 选择1981年1月1日至1998年12月31日期间在香港尘肺诊所登记的2789例男性矽肺病例为研究对象,取用同时期一般男性人群作为对照.用人年的方法估计各死因的标化死亡比(SMR),用Axelson's法间接调整吸烟的混杂影响.矽尘与肺癌的剂量-效应关系采用多因素p-spline平滑法模型来拟合最佳风险模型.结果 该组研究队列人数为2789,共观察24 992.6人年,失访率仅为2.9%.该队列主要工种为建筑工人(5 1.09%)和地下沉箱操作工人(37.54%).队列总死亡人数为853人,平均死亡年龄为(63.8±10.27)岁,整个队列中86例死于肺癌.全死因及全癌的SMR均明显上升,首位死因是呼吸道疾病,肺癌的5MR明显增加(SMR:1.69,95%CI:1.35～2.09).去除年龄、时期和吸烟的混杂因素的影响,矽肺对肺癌的相对危险度下降到1.12(95%CI:0.89～1.38).间接调整吸烟的混杂影响后建筑工人及地下沉箱工人肺癌的相对危险度分别为1.09(95%CI:0.82～1.42)和1.56(0.98～2.36).多因素p-spline平滑法风险模型分析显示,肺癌与累积呼吸性矽尘总量或平均矽尘浓度的关系无剂量-效应关系.结论 队列研究未发现接触矽尘或矽肺能增加肺癌死亡的危险,平滑法模型拟合的风险模型并不支持矽尘与肺癌死亡之间存在剂量-效应关系.