A nested case-control study of lung cancer among silica exposed workers in China.

In an attempt to assess whether silica induces lung cancer, a nested case-control study of 316 male lung cancer cases and 1352 controls was carried out among pottery workers and tungsten, copper-iron, and tin miners from five provinces in south central China. Exposure to dust and silica for each study subject was evaluated quantitatively by cumulative exposure measures based on historical industrial hygiene records. Measurements on confounders such as inorganic arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon were also collected from the worksites. Information on cigarette smoking was obtained by interviews of the subjects or their next of kin. A significant trend of increasing risk of lung cancer with exposure to silica was found for tin miners, but not for miners working in tungsten or copper-iron mines. Concomitant and highly correlated exposures to arsenic and PAHs among tin miners were also found. Risk of lung cancer among pottery workers was related to exposure to silica, although the dose-response gradient was not significant. Risks of lung cancer were significantly increased among silicotic subjects in iron-copper and tin mines, but not in pottery factories or tungsten mines. The results of this study provide only limited support for an aetiological association between silica and lung cancer.     

A nested case-control study of lung cancer among silica exposed workers in China.

In an attempt to assess whether silica induces lung cancer, a nested case-control study of 316 male lung cancer cases and 1352 controls was carried out among pottery workers and tungsten, copper-iron, and tin miners from five provinces in south central China. Exposure to dust and silica for each study subject was evaluated quantitatively by cumulative exposure measures based on historical industrial hygiene records. Measurements on confounders such as inorganic arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon were also collected from the worksites. Information on cigarette smoking was obtained by interviews of the subjects or their next of kin. A significant trend of increasing risk of lung cancer with exposure to silica was found for tin miners, but not for miners working in tungsten or copper-iron mines. Concomitant and highly correlated exposures to arsenic and PAHs among tin miners were also found. Risk of lung cancer among pottery workers was related to exposure to silica, although the dose-response gradient was not significant. Risks of lung cancer were significantly increased among silicotic subjects in iron-copper and tin mines, but not in pottery factories or tungsten mines. The results of this study provide only limited support for an aetiological association between silica and lung cancer.     

The amphibole hypothesis--a nested case-control study of lung cancer and exposure to chrysotile and amphiboles

This paper describes a case control study investigating separately the lung cancer risk of exposure to chrysotile and to amphiboles. Logistic regression models were used to estimate separate exposure-response curves for the two fibre types, controlling for smoking. In the period longer than 15 years before lung cancer diagnosis, smokers above the 90th percentile of cumulative exposure to either chrysotile (OR = 1.8, 95% CI = 0.6-5.2) or amphibole (OR = 2.3, 95% CI = 0.9-6.2) had a somewhat higher risk than those with lower exposure. The author found suggestive evidence of an association between chrysotile and lung cancer, and especially between amphiboles and lung cancer. In this study, cumulative exposures to amphiboles were on average 40 times lower than cumulative exposures to chrysotile, and the author assumes that the amphibole effect would be much higher if the amphibole level of cumulative exposure were the same as that of chrysotile.     

A nested case-control study of prostate cancer and atrazine exposure

Elevated prostate cancer incidence was found at a plant producing atrazine that had an intensive prostate screening program. This study tested the relationship among atrazine exposure, prostate cancer, and the screening program. Twelve cases and 130 control subjects were selected from the original cohort. Prostate screening and occupational histories were abstracted from company records and atrazine exposures were estimated. Hire date was comparable for cases and control subjects. Nearly half of the control subjects and no cases left before the prostate-specific antigen (PSA) screening program. Cases had more PSA tests than control subjects (odds ratio for > or =1 test, 8.54; 95% confidence interval, 1.69-82.20). There was no association between atrazine exposure and prostate cancer when those with > or =1 test were compared. There was no evidence for an association between atrazine and prostate cancer.     

Oesophageal cancer and occupational exposure to rubber: a nested case-control study

Findings for cancer of the oesophagus in the rubber industry are not consistent between studies, and derive from too few studies. Few studies were carried out to examine risks of oesophageal cancer in different departments and the confounding by non-occupational risk factors such as smoking, drinking, and economic status. In this paper these questions have been explored. Following a nested case-control study, the data were used of nine oesophageal cancer deaths during 1973-1995 and 36 controls matched for sex and age from the same cohort of a rubber plant workers. Oesophageal cancer risks for exposure to rubber were assessed, unadjusted and adjusted for non-occupational factors by conditional logistic regression. In grouped analysis, odds ratios (ORs) for oesophageal cancer were found to be 2.67 (95%CI=0.42,17.0) for milling, etc. workers and 1. 40 (95%CI=0.24,7.97) for building workers, who worked for one or more years. No excess risks were found in the remaining three departments. The models for continuous exposure variables indicated that a one-unit year change in the milling, etc. department was associated with a 4% increment in the OR. When adjusted for serum cholesterol level, the 6% increase (OR) was observed. Significant associations between risk for oesophageal cancer and specific exposures or processes within the rubber plant were not found. The slight excess risk for oesophageal cancer in the rubber plant may be related to exposure to dusts and solvents.     

Occupational exposure to crystalline silica and risk of lung cancer: a multicenter case-control study in Europe

BACKGROUND: The role of crystalline silica dust as a possible cause of lung cancer has been controversial. Relatively few large community-based studies have been conducted to investigate the lung cancer risk from exposure to silica at low levels, taking into account potential confounding factors. METHODS: Detailed lifestyle and occupational information were collected from 2852 newly diagnosed cases of lung cancer and 3104 controls between 1998 and 2002 in 7 European countries. For each job held, local experts assessed the probability, intensity, and duration of silica exposure. RESULTS: Occupational exposure to crystalline silica was associated with an increased risk of lung cancer (odds ratio = 1.37; 95% confidence interval = 1.14-1.65). This risk was most apparent for the upper tertile of cumulative exposure (OR = 2.08; 95% CI = 1.49-2.90; P for trend <0.0001), duration of exposure (1.73; 1.26-2.39; P for trend = 0.0001) and weighted duration of exposure (1.88; 1.35-2.61; P for trend <0.0001). We did not observe any interaction beyond a multiplicative model between tobacco smoking and silica exposure. CONCLUSIONS: Our results support the hypothesis that silica is an important risk factor for lung cancer. This risk could not be explained by exposure to other occupational carcinogens or smoking, and it was present for the main histologic types of lung cancer, different sources of silica exposure, and different industrial settings.     

Exposure assessment and modeling of quartz in Swedish iron foundries for a nested case-control study on lung cancer

Exposure assessment of quartz in Swedish iron foundries was performed based on historical and current measurement data. To evaluate the exposure-response relationship between quartz exposure and lung cancer, we modeled quartz exposure from our database of measurements using determinants job title, time period, and company. Based on these modeled exposure data, we conducted a nested case-control evaluation. In our database, the overall individual, daily time-weighted average (TWA) quartz concentrations of current and historical data varied between 0.0018 and 4.9 mg/m(3), averaging 0.083 mg/m(3). Job titles with mean TWAs for the whole study period exceeding the European Union recommended occupational exposure limit of 0.05 mg/m(3) were fettlers (0.087 mg/m(3)), furnace and ladle repair (0.42 mg/m(3)), and maintenance (0.054 mg/m(3)) workers. The mixed model analysis demonstrated significant determinants on the job level for furnace and ladle repair (β = 4.06; 95% confidence interval [CI] 2.78-5.93). For all jobs, significantly higher exposure levels occurred only during the first time period, 1968-1979 (β = 2.08; 95% CI 1.75-2.47), and a decreasing but not significant trend was noted for the three following 10-year time periods up to 2006 (β = 1.0, 0.96 and 1, respectively). Two iron foundries had significantly higher quartz concentration levels than the others (β = 1.31; 95% CI 1.00-1.71 and β = 1.63; 95% CI 1.00-2.65, respectively). The individual cumulative quartz exposure measures were categorized in low, medium, and high exposure (0.5-<1, 1-1.9 and ≥ 2 mg/m(3)*years, respectively). In the nested case-control analysis, we found the highest odds ratios of lung cancer (OR 1.17; 95% CI 0.53-2.55) for the medium exposure group. No dose-response trend or significantly increased risk was determined for our high exposed group (≥2 mg/m(3)), representing 40 years of exposure at >0.05 mg/m(3) of quartz. To conclude, certain foundry workers are still exposed to high levels of quartz, but an increased risk of lung cancer caused by quartz exposure in these Swedish iron foundries could not be confirmed at our exposure levels.     

Effects of work related confounders on the association between silica exposure and lung cancer: a nested case-control study among Chinese miners and pottery workers

Objective The role of silica in the causation of lung cancer is an ongoing debate. In order to explore whether observed association between silica exposure and lung cancer is confounded by exposure to other occupational carcinogens, we updated a previously nested case-control study among a cohort of male workers in 29 Chinese mines and factories on the basis of an extended follow-up. Methods Five hundred and eleven lung cancer cases and 1,879 matched controls were selected. Exposure to respirable silica as well as relevant occupational confounders were quantitatively assessed based on historical industrial hygiene data. The relationship between exposure to silica and lung cancer was analyzed by conditional logistic regression analysis adjusted for exposure to arsenic, polycyclic aromatic hydrocarbons (PAHs), radon, and smoking. Results In a crude analysis adjusted for smoking only, a significant trend of increasing risk of lung cancer with exposure to silica was found for tin, iron/copper miners, and pottery workers. But after adjustment for relevant occupational confounders, no relationship between silica and lung cancer can be observed. Instead, there is a significant association between lung cancer mortality and cumulative exposure to inorganic arsenic (OR = 1.86, 95% CI: 1.14, 3.04 for each mg/m³-year increase) and carcinogenic PAHs (OR = 1.35, 95% CI: 1.08, 1.69 for each 100 μg/m³-year increase). Conclusion This analysis does not provide any evidence to show that exposure to silica causes lung cancer in the absence of confounding factors.     

Asbestos fibreyears and lung cancer: a two phase case-control study with expert exposure assessment

Aims: To assess the cumulative effect of asbestos on lung cancer risk where the exposure is assessed by an expert rating.

Methods: 1678 male cases and controls were enrolled in a population based matched case–control study, focused on occupational risk factors, carried out in West Germany. The exposure to asbestos was computed as lifelong working hours. For a validation subsample of 164 matched pairs from this study the intensity of asbestos exposure was further assessed by a panel of experts in order to obtain an estimate of the cumulative exposure on a time by intensity scale (fibreyears). The information on duration of asbestos exposure in the original study was combined with the fibreyears following the two phase case control study paradigm.

Results: The number of exposed subjects in the validation subsample was 75 cases and 71 controls. The percentage of subjects with a cumulative exposure ≤1, 1 to ≤10, and >10 fibreyears was 16%, 15%, and 15% for the cases and 18%, 16%, and 9% respectively for the controls. The smoking adjusted odds ratios for the fibreyears based on an unconditional logistic regression were 0.81, 1.02, and 1.60 respectively with increasing exposure categories (not significant). The coefficient (beta) for a log transformed trend was 1.156. Applying the two phase paradigm, these odds ratios became 0.86, 1.33, and 1.94; the latter reached significance and the beta coefficient was 1.178.

Conclusions: The two phase paradigm allowed us to obtain a more precise estimate of the effect of asbestos on lung cancer. Results are consistent with a doubling of the lung cancer risk with 25 fibreyears asbestos exposure.

     

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.     

环境低浓度石棉暴露与肺癌危险性的巢式病例对照研究

目的探讨云南省大姚县环境低浓度青石棉暴露与肺癌之间的关联以及肺癌高发的主要危险因素，为当地的肺癌防制提供依据。方法采用巢式病例对照研究方法，从队列中获得53例肺癌病例，按1：3的比例分别匹配以性别相同、年龄相当的对照。结果单因素条件logistic回归分析发现石棉环境污染、吸烟、饮酒、喝茶与肺癌有统计学关联，石棉环境污染的各种形式中，只有使用石棉炉对肺癌发生有显著性意义。用多因素条件logistic回归进一步分析，使用石棉炉和吸烟与肺癌有统计学关联，OR值分别是3．38(95％CI1．43～7．95)和2．62(95％CI1．08～6．56)．其他各因素对肺癌的影响未发现有显著性意义。对吸烟与使用石棉炉的交互作用进行相乘模型的拟合，未发现两因素存在相乘模型的交互作用(P=0．310)。相加模型交互作用分析结果显示，吸烟和使用石棉炉对肺癌发病的影响可能存在着相加模型的交互作用。结论吸烟和使用石棉炉是当地肺癌高发的主要危险因素，且两者存在着相加模型的交互作用。     

Epidemiological adaptation of quartz exposure modeling in Swedish aluminum foundries: nested case-control study on lung cancer

In a recent cohort study in aluminum foundries and remelting plants an unexpectedly high risk of lung cancer was found in workers in sand foundries. On the basis of present and historical measurement data, we developed a statistical model for exposure to total dust and crystalline quartz for different jobs and time periods. Cumulative dose estimates of total dust and crystalline quartz were calculated and used in a nested case-control study in the cohort. From the cohort of foundry workers (n = 5016), 46 cases of lung cancer were identified. The final analysis was performed on 31 cases and 233 controls with one year or more of employment. Historical measurement data from the 1960s and onward were collected, totaling 203 total dust and 103 crystalline quartz exposure observations. Regression models, using the determinants of job title, time period, type of foundry, and size of production, were developed for assessing historical total dust and crystalline quartz air concentrations. These estimates were used to calculate individual cumulative exposure in the case-control study. In the multiple linear regression analysis, the determinants explained much of the variations in dust level (r(2) = 0.58). The explained variation in crystalline quartz was much lower (r(2) = 0.13). The regression coefficients for the type of foundry, time period, and size of production were statistically significant for total dust. On the basis of the regression analysis, the final models were used to calculate individual cumulative exposures. The calculated cumulative dust and quartz exposures averaged 33 mg/m(3) * year and 0.42 mg/m(3) * year, respectively. The odds ratios (ORs) were not significant, but showed dose-response trends for both dust and crystalline quartz.     

Silica exposure and lung cancer in ceramic workers: a case-control study

The results are presented from a case-control study, concerning the possible relation between silica exposure in the Dutch fine ceramic industry and lung cancer. For this purpose 381 male, age-matched pairs of primary lung cancer cases and controls were selected from the pathology department of the University Hospital in the region, where two large ceramic companies are located. Information about employment in the ceramic industry was obtained from the personnel and financial administration departments of the two companies. On the basis of job titles a panel of occupational hygiene experts reached consensus about the qualitative exposures of each individual worker. Twenty one per cent of the cases were employed in the ceramic industry, compared with 19% of the controls (odds ratio 1.11; 95% Cl: 0.77-1.61). Although the average employment period of cases and their relative silica exposure surpassed those of controls, odds ratios for long duration of employment and considerable exposure to respirable silica dust did not reach statistical significance. After constructing a qualitative exposure index, based on the amount and duration of exposure, a tendency towards a positive correlation with lung cancer emerged. No relation between specific histological tumour cell types and working in the ceramic industry emerged. Although the study does not suggest a consistent cause-effect relation between silica exposure in the regional, Dutch fine ceramic industry and lung cancer, an increased risk for the high exposure group in the past can not be totally excluded.     

A validation of information on occupation--data from a nested case-control study

OBJECTIVES: To evaluate the validity of information about employment obtained from self-respondents and proxies in a nested case-control study. METHODS: We interviewed 230 self-respondents and 652 proxies covering 237 cancer cases and 645 controls. Questions about employment as a bus driver, other jobs, and residence were asked. Golden standard was employment data obtained from personnel records. RESULTS: All categories of respondents tended to over-report the length of employment, and respondents aged above 70 years had significantly decreased odds ratio for disagreement between interview and company files compared with respondents below the age of 60 years. There were no significant differences in whether the respondent was a case or control as there were no differences in whether the respondent was a self-respondent or a proxy. The validity of the reported employment time was statistically independent of the interval between death and proxy contact. Compared with the self-responders, the proxies reported significantly fewer jobs and residential areas. CONCLUSIONS: In general, data obtained from cases and controls not knowing that the study was about cancer and without the interviewer's knowing who were cases and who were controls appeared good. The quality of information obtained from proxies appeared good as well. There seems to be no problem in interviewing very old people about a specific job when they are mentally prepared for it. The time interval between death and proxy contact was without importance.     

Leukemia mortality and occupational exposure to rubber: a nested case-control study

OBJECTIVE: The excess risk of leukemia in rubber industry was considered to be real and attributed to the exposure to solvents, particularly benzene. METHODS: Following a nested case-control study, we used the data of 7 leukemia deaths in 1973-1997 and 28 controls matched for sex and age from the same cohort of a rubber plant. Leukemia risks due to exposure to rubber were assessed, unadjusted and adjusted for non-occupational factors by conditional logistic regression. RESULTS: OR for leukemia was found to be 7.81 (95% CI = 0.77-78) in grouped analysis for one or more years of work in the inner tire tube department. The models for continuous exposure variables indicated that working for one year in the inner tire tube department was associated with a 10 percent increment in the OR (95% CI = 1.00-1.24; score test for linear trend: chi 1(2) = 6.27, P = 0.012). The confounding effects studied could not be ruled out for the excess risks. No excess risk was found in the remaining four departments. CONCLUSIONS: Because of widespread exposure to various carcinogens in the process of making inner tire tubes, removal of a single agent (benzene) may not eliminate the risk of leukemia in the entire industry.     

Exposure to beryllium and occurrence of lung cancer: a reexamination of findings from a nested case-control study

OBJECTIVE: Our aim was to reanalyze a nested case-control study of beryllium and lung cancer because we identified analysis and study design issues that could have led to the elevated odds ratios obtained in the study. METHODS: We reanalyzed the data using nontransformed exposure metrics instead of log-transformed metrics used in the publication. We identified and examined effects on estimated odds ratios of imbalances between cases and controls caused by the control selection method. RESULTS: This reanalysis found no elevated odds ratios for any exposure variable. CONCLUSION:: Our conclusions differ from the authors' interpretation that the findings are due to a causal relationship between beryllium exposure and lung cancer. Our alternative explanation is that they may be due to methodological problems that could have been controlled by closer matching of controls to cases. CLINICAL SIGNIFICANCE: This study challenges conclusions made from a large case-control study concerning beryllium-lung cancer associations. Occupational medicine practitioners may want to integrate findings from this study into advice they give beryllium-exposed workers concerned about lung cancer.     

Plasma enterolignan concentrations and colorectal cancer risk in a nested case-control study

Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis. The authors investigated the association between plasma enterolactone and enterodiol and colorectal cancer risk in a Dutch prospective study. Among more than 35,000 participants aged 20-59 years, 160 colorectal cancer cases were diagnosed after 7.5 years of follow-up (1987-2003). Cohort members who were frequency-matched to the cases on age, sex, and study center were selected as controls (n = 387). Plasma enterodiol and enterolactone were not associated with risk of colorectal cancer after adjustment for known colorectal cancer risk factors (highest quartile vs. lowest: for enterodiol, odds ratio = 1.11, 95% confidence interval: 0.56, 2.20 (p-trend = 0.75); for enterolactone, odds ratio = 1.70, 95% confidence interval: 0.88, 3.27 (p-trend = 0.15)). However, sex (p-interaction = 0.06) and body mass index (p-interaction < 0.01) modified the relation between plasma enterolactone and colorectal cancer risk; increased risks were observed among women and subjects with a high body mass index. The association between plasma enterodiol and colorectal cancer risk was modified by smoking status; risk was increased among current smokers (p-interaction < 0.01). These findings do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with reduced risk of colorectal cancer.     

Occupation and lung cancer in Shanghai: a case-control study.

Occupation was evaluated as a potential risk factor for lung cancer as part of a large population based case-control study conducted in the ten urban districts of Shanghai. A total of 733 newly diagnosed cases of male lung cancer and 760 controls selected from the general population was interviewed to obtain lifetime occupational histories and information on smoking and other factors. Of the approximately 25 major industrial titles examined, significantly raised risks, adjusted for smoking, were found for employment in agricultural production (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.0-2.6). A concomitant increase was detected for farmers (OR = 1.6, 95% CI = 1.0-2.5) when 35 major occupational titles were examined. There was a 70% excess among workers in the chemical industry (OR = 1.7, 95% CI = 0.9-3.1) and a significant decrease among textile industry workers (OR = 0.7, 95% CI = 0.5-1.0). Raised risks of 30% to 80% were associated with reported job exposures to wood and coal dusts, smoke from burning fuels, and chemical fumes. Employment categories were also examined for 672 cases and 735 controls among women, but small numbers in many of the industrial and occupational categories precluded detailed analyses. The largest excess risk among women (OR = 5.1, 95% CI 1.3-23.5) was among glass products workers. Although cigarette smoking was the dominant cause of lung cancer among men and a significant risk factor among women in Shanghai, these findings suggest the importance of certain workplace exposures and offer leads to occupational carcinogens.