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 silicotic patients in Sardinia: an update study with 10 more years of follow up

OBJECTIVES—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.METHODS—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.RESULTS—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.CONCLUSIONS—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.     

Reevaluation of silicosis and lung cancer in North Carolina dusty trades workers.

We previously reported on the lung cancer mortality through 1983 of 760 males who were diagnosed with silicosis during 1930-1983 by the State of North Carolina's medical examination program for dusty trades workers. The lung cancer SMR (95% confidence interval) was 2.6 (1.8-3.6) among 655 white members of this group. In this paper, we report the results of a reanalysis of mortality among a subgroup for whom chest radiographs were currently available for rereading. Technically acceptable radiographs were available for 306 white males and were independently reclassified for pneumoconiosis by 3 "B" readers using the 1980 ILO Classification. Lung cancer SMRs were 1.7 (0.8-3.1) for the entire group of 306 white males, 2.5 (1.1-4.9) for 143 subjects reclassified as simple silicosis, and 1.0 (0.1-3.5) for 96 subjects whose radiographs were reclassified as ILO category 0. There were no lung cancer deaths among 67 subjects whose radiographs were reclassified as progressive massive fibrosis. Corresponding lung cancer SMRs for subjects who had never been employed in a job with exposure to known occupational carcinogens were 1.2 (0.2-4.4) for those reclassified as category 0, and 2.4 (1.0-5.0) for those reclassified as having simple silicosis. The age-adjusted lung cancer rate ratio among subjects with simple silicosis compared to those with category 0 was 1.5 (0.4-5.8). Our findings from this reanalysis, which effectively controls for misclassification of silicosis due to errors in radiograph interpretation by North Carolina program readers, offer additional evidence consistent with the hypothesis of an association between silicosis and lung cancer in this study group.     

Radiographic silicosis and lung cancer risk among workers in Ontario

A case-control study, nested in a cohort of workers under surveillance for silicosis in 1979 or later, was undertaken to assess lung cancer risk in relation to the ILO coding scheme for the pneumoconioses. The subjects of this study are from the 41 matched quartets, consisting of one worker with silicosis and three age-matched controls, in which a lung cancer case was diagnosed. The odds ratio for lung cancer among subjects with ILO classification 1/0 or more, in comparison to subjects with category ≤ 0/1, was 3.27 (95%CI = 1.32–8.2). Adjustment of the radiographic risk for the effect of cumulative radon exposure had the effect of increasing the odds ratio for the association between ILO category ⩾1/0 and lung cancer. Although small smoking differences could account for the increased lung cancer odds ratio among workers with silicosis, the empirical evidence suggests that these smoking differences do not exist. It is concluded on the basis of two North American studies of silica exposed workers that radiographic silicosis is a marker for an increased risk of lung cancer. Am. J. Ind. Med. 34:244–251, 1998. © 1998 Wiley-Liss, Inc.     

Case-control study of silicosis, silica exposure, and lung cancer in white South African gold miners

A case-control study was undertaken to assess the association between lung cancer and silicosis or silica dust exposure in white South African gold miners. Cases and controls were identified from deaths reported to the Gold Miners Provident Fund for the period January, 1979-October, 1983. Two controls were matched to each case by year of birth (+/- 2 years) and by smoking (+/- 5 cigarettes or equivalents per day) assessed 10 years (+/- 2 years) prior to death. One hundred thirty-three matched triplets were identified. The results showed no overall association between lung cancer and radiological silicosis (OR = 1.08, p = 0.92). Autopsy data indicated no overall associations between lung cancer and silicosis of the lung parenchyma (OR = 1.49, p = 0.11), the pleura (OR = 0.72, p = 0.30), or the hilar glands (OR = 0.85, p = 0.72). A trend toward increased severity of silicosis of the parenchyma was evident; however, this was not statistically significant (p = 0.08). Odds ratios for lung cancer and silicosis were higher at lower levels of cumulative silica dust exposure (ORs = 2.43, 1.72, 1.35 and 0.62 for lung cancer and autopsy silicosis of the parenchyma for the lowest, second, third, and highest quartiles of dust exposure, respectively; all p greater than 0.05). Cases did not differ from controls for total silica dust exposure, length of exposure, weighted average intensity of exposure, or number of shifts at high dust (all p greater than 0.20). The data do not support the hypothesis of a carcinogenic role for silica dust and no statistically significant associations were found between lung cancer and silicosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic obstructive pulmonary disease due to occupational exposure to silica dust: a review of epidemiological and pathological evidence

Occupational exposure is an important risk factor for chronic obstructive pulmonary disease (COPD), and silica dust is one of the most important occupational respiratory toxins. Epidemiological and pathological studies suggest that silica dust exposure can lead to COPD, even in the absence of radiological signs of silicosis, and that the association between cumulative silica dust exposure and airflow obstruction is independent of silicosis. Recent clinicopathological and experimental studies have contributed further towards explaining the potential mechanism through which silica can cause pathological changes that may lead to the development of COPD. In this paper we review the epidemiological and pathological evidence relevant to the development of COPD in silica dust exposed workers within the context of recent findings. The evidence surveyed suggests that chronic levels of silica dust that do not cause disabling silicosis may cause the development of chronic bronchitis, emphysema, and/or small airways disease that can lead to airflow obstruction, even in the absence of radiological silicosis.     

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.     

Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories: the modifying role of other workplace lung carcinogens.

BACKGROUND: Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer. METHODS: We used data from a nested case-control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and 1 clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory. RESULTS: In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon-daughters, was considered. The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred. CONCLUSIONS: Our results suggest that, among silica-exposed Chinese workers, numerous occupational and non-occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica.     

Radiographic readings for asbestosis: misuse of science--validation of the ILO classification

BACKGROUND: Radiographic readings for pneumoconiosis (both asbestosis and silicosis), even those using the International Labour Office (ILO) Classification, have received widespread negative coverage in the media and strong judicial rebuke. METHODS: The medical literature over the past 90 years was reviewed for the relationships between radiographic severity (standardized as the ILO profusion score) and indices of exposure to silica or asbestos, tissue burden of silica particles or asbestos fibers, histologic fibrosis, various measurements of pulmonary function and mortality. RESULTS: Evidence from many different disciplines has demonstrated that the ILO profusion score correlates with occupational exposure, dust burden in the lung, histologic fibrosis and, more recently, with physiologic impairment and mortality. CONCLUSIONS: The ILO Classification has therefore been validated as a scientific tool. Its fraudulent misuse by "hired-gun" physicians, attorneys and elements of the compensation system to falsify claims of asbestosis and/or silicosis (often in the same claimant) must be condemned.     

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.     

Respiratory cancer and other chronic disease mortality among silicotics in california

Silicotics have increased mortality from tuberculosis (TB) and from nonmalignant respiratory diseases (NMRD), including silicosis and silicotuberculosis. Since the publication of the International Agency for Research on Cancer monograph in 1987 indicating that silica was a probable human carcinogen, there has been an extensive debate about the cancer risks among silicotics. The authors identified 590 claims for silicosis among a registry of lung diseases compiled from California Workers' Compensation cases from 1945 to 1975. Using state vital records, we determined the mortality risks from 1946 to 1991. Our findings confirmed that these claimants had a significantly elevated risk for all causes of death with a standardized mortality ratio (SMR) of 1.30 (95% confidence interval [CI] = 1.18, 1.43); TB had a SMR of 56.35 (95% CI = 41.10, 75.40) and NMRD a SMR of 3.80 (95% CI = 3.11, 4.60). Cancers of the trachea, bronchus, and lung had a SMR of 1.90 (95% CI = 1.35, 2.60). For malignancies of the large intestine, there was a previously unreported SMR of 2.08 (95% CI = 1.14, 3.50). Mortality from all diseases of the heart was significantly less than expected with a SMR of 0.68 (95% CI = 0.55, 0.83); cancers of the prostate and lymphatic system were also significantly low with SMRs of 0.26 (95% CI = 0.03, 0.94) and 0.17 (95% CI = 0.04, 0.97), respectively. Workers with silicosis should be warned about these chronic disease risks, and prevention efforts to control occupational silica dust exposure should become a higher priority.     

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.     

Mortality experience of haematite mine workers in China

The mortality risk of iron ore (haematite) miners between 1970 and 1982 was investigated in a retrospective cohort study of workers from two mines, Longyan and Taochong, in China. The cohort was limited to men and consisted of 5406 underground miners and 1038 unexposed surface workers. Among the 490 underground miners who died, 205 (42%) died of silicosis and silicotuberculosis and 98 (20%) of cancer, including 29 cases (5.9%) of lung cancer. The study found an excess risk of non-malignant respiratory disease and of lung cancer among haematite miners. The standardised mortality ratio for lung cancer compared with nationwide male population rates was significantly raised (SMR = 3.7), especially for those miners who were first employed underground before mechanical ventilation and wet drilling were introduced (SMR = 4.8); with jobs involving heavy exposure to dust, radon, and radon daughters (SMR = 4.2); with a history of silicosis (SMR = 5.3); and with silicotuberculosis (SMR = 6.6). No excess risk of lung cancer was observed in unexposed workers (SMR = 1.2). Among current smokers, the risk of lung cancer increased with the level of exposure to dust. The mortality from all cancer, stomach, liver, and oesophageal cancer was not raised among underground miners. An excess risk of lung cancer among underground mine workers which could not be attributed solely to tobacco use was associated with working conditions underground, especially with exposure to dust and radon gas and with the presence of non-malignant respiratory disease. Because of an overlap of exposures to dust and radon daughters, the independent effects of these factors could not be evaluated.     

Mortality experience of haematite mine workers in China.

The mortality risk of iron ore (haematite) miners between 1970 and 1982 was investigated in a retrospective cohort study of workers from two mines, Longyan and Taochong, in China. The cohort was limited to men and consisted of 5406 underground miners and 1038 unexposed surface workers. Among the 490 underground miners who died, 205 (42%) died of silicosis and silicotuberculosis and 98 (20%) of cancer, including 29 cases (5.9%) of lung cancer. The study found an excess risk of non-malignant respiratory disease and of lung cancer among haematite miners. The standardised mortality ratio for lung cancer compared with nationwide male population rates was significantly raised (SMR = 3.7), especially for those miners who were first employed underground before mechanical ventilation and wet drilling were introduced (SMR = 4.8); with jobs involving heavy exposure to dust, radon, and radon daughters (SMR = 4.2); with a history of silicosis (SMR = 5.3); and with silicotuberculosis (SMR = 6.6). No excess risk of lung cancer was observed in unexposed workers (SMR = 1.2). Among current smokers, the risk of lung cancer increased with the level of exposure to dust. The mortality from all cancer, stomach, liver, and oesophageal cancer was not raised among underground miners. An excess risk of lung cancer among underground mine workers which could not be attributed solely to tobacco use was associated with working conditions underground, especially with exposure to dust and radon gas and with the presence of non-malignant respiratory disease. Because of an overlap of exposures to dust and radon daughters, the independent effects of these factors could not be evaluated.     

Silica,compensated silicosis,and lung cancer in Western Australian goldminers

OBJECTIVES: Silica has recently been reclassified as carcinogenic to humans based largely on the observed increase in rates of lung cancer in subjects with silicosis. Other recent reviews have arrived at different conclusions as to whether silicosis or silica itself is carcinogenic. This study aims to examine exposure-response relations between exposure to silica and subsequent silicosis and lung cancer in a cohort of goldminers. METHODS: 2,297 goldminers from Kalgoorlie in Western Australia were examined in 1961, 1974, and 1975. Data were collected on respiratory symptoms, smoking habits, and employment history. Subjects were followed up to the end of 1993. Survival analyses for lung cancer mortality and incidence of compensated silicosis were performed with age and year matched conditional logistic regression analyses. RESULTS: 89% of the cohort were traced to the end of 1993. 84% of the men had smoked at some time and 66% were current smokers. 1386 deaths occurred during the follow up period, 138 from lung cancer, and 631 subjects were compensated for silicosis. A strong effect of smoking on mortality from lung cancer, and a smaller effect on the incidence of compensated silicosis was found. There was a strong effect of duration and intensity of exposure on the incidence of silicosis. The risk of mortality from lung cancer increased after compensation for silicosis. Of all direct measures of exposure to silica, only log cumulative exposure was significantly related to incidence of lung cancer, but this effect disappeared once the onset of silicosis was taken into account. CONCLUSIONS: The incidence of silicosis was clearly related to exposure to silica and the onset of silicosis conferred a significant increase in risk for subsequent lung cancer, but there was no evidence that exposure to silica caused lung cancer in the absence of silicosis.       

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.     

不同类型厂矿接尘工人肺癌病因学研究──矽尘或矽肺与肺癌的关系

为评价游离二氧化硅（简称矽尘或ＳｉＯ２）是否致肺癌？矽肺是否是肺癌前变基础？选择四类接尘厂矿进行队列和队列内病例对照研究。队列对象６８２８５人。有矽肺６４８７例，肺癌３３０例（男３１９，女１１），配对照１３５８例。根据厂矿历年工业卫生记录和近期对已知致癌物监测结果，定量评估了每个对象的接尘水平及每个病例对照的累积接触量。研究对象追访到１９８９年底，死亡６１９２人。与全国居民死亡平均数计算的期望值近似。全死因中癌症是第一死因，但全癌低于国家居民死亡率。分析结果说明：（１）矽尘单独存在时不是肺致癌剂。肺癌不超高，与接尘关系不明显；（２）在６４８７名矽肺队列中，肺癌相对危险度仅比非矽肺高０．２２倍，主要反应在铜铁矿工人中（Ｒ＝２．２），而矽肺患病率最严重的钨矿工人，其肺癌危险度反而随接尘水平上升而下降，再则肺癌死亡率与矽肺期别不呈正比；形态学上观察也不支持肺癌病变与矽肺纤维化病变相关。本研究结果难以支持矽尘或矽肺与肺癌病因学相关的假说。     

A case-control study of lung cancer in relation to silica exposure and silicosis in a rural area in Japan

PURPOSE: In southeast Okayama Prefecture, Japan, there have been reports of a high prevalence of silicosis among refractory brick production workers. Recently, a high mortality rate of lung cancer among the local residents has been observed. Therefore, a population based case-control study was conducted concerning the relationship between silica, silicosis, and lung cancer using multiple cancer controls. METHODS: Cases and controls were restricted to male subjects and information was obtained from death certificates from 1986 to 1993 in the area. Three categories of deceased control groups were selected: a series of deaths from liver cancer, colon cancer, and cancers of other organs, which was assumed not to be related to silica exposure. Age and smoking habits were adjusted by stratified analysis using the Mantel-Haenszel odds ratio estimates. Unconditional logistic regression analysis was also conducted to control potential confounding factors; such as age and smoking habits. RESULTS: The age-, smoking-adjusted odds ratios were 1.94 (0.94-4.43) for the colon cancer control group, 2.13 (1.19-3.85) for the other cancer control group related to silica exposure, and 2.94 (1.30-8.90) and 2.69 (1.43-5.37) related to silicosis, respectively. The direct weighted average using the estimates for colon and the other cancer controls was 2.06 (1.29-3.29) for silica exposure, and 2.77 (1.60-4.77) for silicosis. Histological or cytological types of lung cancer cases were obtained from 64.1% of the subjects (118/184). As for the histologic type of lung cancer, small cell carcinoma was higher among those who had been silica-exposed workers than the unexposed lung cancer cases and the data from the general Japanese population. On chest x-ray findings, elevated lung cancer mortality compared with cancers other than lung cancer was demonstrated among patients without large opacities. CONCLUSIONS: Silica exposure increased the lung cancer mortality in the area. A high lung cancer mortality rate in the area could be explained by silica exposure and silicosis prevalence in this area.     

Mortality from lung and kidney disease in a cohort of North American industrial sand workers: an update

BACKGROUND: A previously published cohort study of some 2670 employees of the North American sand industry, followed through 1994, provided strong evidence of a causal relationship between quartz exposure and death from both silicosis and lung cancer, after allowance for cigarette smoking and in the absence of known occupational carcinogens. Unexpectedly, a significant excess mortality from chronic non-malignant renal disease [observed 16; expected 7.6; standardized mortality ratio (SMR) 212] was also found, whereas deaths from renal cancer at this stage were close to expectation (observed 6; expected 5.2). OBJECTIVES: Our primary aim was to discover whether death from chronic renal disease was related to the estimated intensity of crystalline silica exposure. A further aim was to determine whether or not our previous estimates of lung cancer and silicosis risk were confirmed by mortality in the cohort 6 years later. METHODS: With help from the US National Death Index, surviving members of the cohort, with the exception of employees of a small plant in Canada, were traced through 2000. The cause of death was determined for all who had died, for comparison against National and State mortality rates. Nested case-referent analyses were then undertaken, as previously, of deaths from lung cancer and silicosis, plus end-stage renal disease and kidney cancer, in relation to quantitative re-estimates of quartz exposure. RESULTS: The total number of deaths through 1994 was 990; there were 231 additional deaths during the period 1995-2000. The SMRs were significantly higher in the later than the earlier period, mainly due to a relative increase in heart disease and external causes. The updated odds ratios for lung cancer and silicosis were almost identical to those published previously, with lung cancer risk again related to average silica concentration and cumulative exposure, but not to length of employment. In contrast, risks of neither end-stage renal disease nor renal cancer were related to cumulative exposure, although now based on 19 cases (SMR 239), and 10 cases (SMR 202), respectively, in fact, opposite trends were apparent for both diseases. However, because of the small numbers there was only limited power to assess the statistical significance of these trends or of any separate relationship with the duration or intensity of exposure. CONCLUSIONS: Our findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of other known carcinogens, but failed to find similar evidence to explain the excess mortality from either chronic renal disease or kidney cancer.     

Vermont granite mortality study: an update with an emphasis on lung cancer

This mortality study extends the period of observation of an article published in 1988 of 5414 workers in Vermont granite sheds and quarries to assess whether previously reported reductions in silicosis and tuberculosis mortality were maintained. The relationship between lung cancer and quartz exposure is also examined by comparing mortality in workers hired before and after 1940, when dust controls were introduced and exposures were reduced by 80% to 90%. Before 1940, general stone shed air contained 20 million particles/cubic foot (mppcf) (approximately equivalent to 0.2 mg/m of quartz), and pneumatic chisel workers were exposed on average to 60 mppcf (approximately equivalent to 0.6 mg/m of quartz). Other workers had variable exposures. After 1940, a period of decline occurred in dust levels and then stabilized in approximately 1955, when average dust levels were 5 to 6 mppcf (equivalent to 0.05-.06 mg/m of quartz). Dust exposures in the Vermont industry is considered to be free of confounding occupational substances such as arsenic, although cigarette smoking was common. By the end of 1996, 2539 workers, or 46.9% of the cohort, had died. There were no silicosis deaths in workers hired after 1940 who were exposed only in the Vermont granite industry, illustrating the effect of lowering quartz exposures. Tuberculosis caused 2 deaths in those hired after 1940 (standardized mortality ratio [SMR] = 0.52; not significant). Overall lung cancer mortality was elevated in shed workers who had been exposed both to high levels of quartz before 1940 and to the lower levels prevailing after 1940 (SMR = 1.32; P < 0.01). Quarry workers did not show an excess of lung cancer (SMR = 0.73; not significant). When shed workers with high and low exposure histories (before and after 1940) but with comparable latency and tenure were contrasted, lung cancer mortality was similar. Differing levels of quartz exposure, which resulted in large differences in the mortality experience from silicosis, did not result in differences in lung cancer mortality. The results do not support the hypothesis that granite dust exposure has a causal association with lung cancer.