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.       

Cohort mortality study of North American industrial sand workers. II. Case-referent analysis of lung cancer and silicosis deaths

BACKGROUND: A cohort mortality study of 2670 men in nine North American industrial sand plants resulted in 83 deaths from lung cancer 20 or more years after hire (standardized mortality ratio 139) and 37 deaths from silicosis (including seven from silico-tuberculosis). The lung cancer excess was unrelated to duration of employment and not found in all plants.Objectives: The primary aim was to determine whether lung cancer risk among these employees was related to quantitative estimates of crystalline silica exposure, after allowance for cigarette smoking. A secondary aim was to do the same for silicosis mortality, partly as a means of validating the estimated levels of exposure. METHODS: A nested case-referent study was undertaken with cases matched with up to two controls on plant, age and date of first employment from men who survived the case. Exposures were estimated by linking work histories to a job-exposure matrix, undertaken separately. Cigarette smoking information was obtained from medical records and other sources, blind as to case-control status. Matched statistical analyses were conducted using conditional logistic regression. FINDINGS: Odds ratios for silicosis mortality were significantly related to cumulative silica exposures and tended to a relationship with category of average crystalline silica concentration, but inconsistently with length of employment. After accounting for a strong effect of cigarette smoking, odds ratios for lung cancer were related to cumulative crystalline silica exposure and to average silica concentration, but not to length of employment. CONCLUSION: These findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of cristobalite or other known occupational carcinogens.     

Mortality of workers compensated for silicosis during the period 1959-1963 in the Veneto region of Italy

After reports appeared from other countries indicating an excess risk of lung cancer among silicotics, a cohort of workers compensated for silicosis during the period 1959-1963 in the Veneto region of Italy was constructed and followed for mortality through 1984. The results of the study showed a large mortality excess for infectious diseases (180 observed versus 9.5 expected), due to silicotuberculosis, and for diseases of the respiratory system (270 observed versus 33.5 expected) due to silicosis. An elevated standardized mortality ratio of 239 (70 observed versus 29.3 expected) from lung cancer was also detected. An increasing pattern was observed with time since first exposure, while the relationship with employment category and duration of exposure was less clear-cut. The lung cancer excess was also strongly associated with cigarette smoking, there being a dose-response relationship with daily cigarette consumption. The study confirms the results from other epidemiologic studies on silicotics which show this pathological condition to be associated with increased lung cancer mortality.     

Mortality in gold and coal miners in Western Australia with special reference to lung cancer.

Cohorts of 1974 gold miners and 213 coal miners in Western Australia surveyed for respiratory symptoms, smoking habits, occupational history and radiographic evidence of pneumoconiosis have been followed up for 13-14 years. Overall, neither group had a significantly higher mortality than expected from the experience of Western Australian men in general. Lung cancer mortality was relatively high in the gold miners (59 deaths observed, 40.8 expected) but weakly and inconclusively related to the extent of their underground mining experience. Cigarette smoking may explain the excess of lung cancer in the gold miners because the prevalence of the habit in the latter (66.3%) was higher than in the coal miners (58.7%) or in other men in Western Australia (53.2%). Radiographic evidence of silicosis was present in 21.7% of the gold miners but did not appear to have contributed substantially to their mortality. The coal miners showed a lower than expected rate of lung cancer but an excess of deaths from all other forms of cancer (11 observed, 5.6 expected). This excess was not attributable to any one cancer site and cannot be explained readily.     

Mortality in gold and coal miners in Western Australia with special reference to lung cancer.

Cohorts of 1974 gold miners and 213 coal miners in Western Australia surveyed for respiratory symptoms, smoking habits, occupational history and radiographic evidence of pneumoconiosis have been followed up for 13-14 years. Overall, neither group had a significantly higher mortality than expected from the experience of Western Australian men in general. Lung cancer mortality was relatively high in the gold miners (59 deaths observed, 40.8 expected) but weakly and inconclusively related to the extent of their underground mining experience. Cigarette smoking may explain the excess of lung cancer in the gold miners because the prevalence of the habit in the latter (66.3%) was higher than in the coal miners (58.7%) or in other men in Western Australia (53.2%). Radiographic evidence of silicosis was present in 21.7% of the gold miners but did not appear to have contributed substantially to their mortality. The coal miners showed a lower than expected rate of lung cancer but an excess of deaths from all other forms of cancer (11 observed, 5.6 expected). This excess was not attributable to any one cancer site and cannot be explained readily.     

Mortality experience of male workers at a UK tin smelter

BACKGROUND: Between 1937 and 1991, Capper Pass and Sons Limited operated a tin smelter complex in North Humberside, UK, at which employees were potentially exposed to a number of substances, including lead, arsenic, cadmium and natural series radionuclides. Decommissioning and site clearance continued until 1995. Between 1967 and 1995 the company was a subsidiary of Rio Tinto plc. AIMS: The aim was to identify any significant excess, or deficits, in mortality among former employees that might be attributable to factors associated with occupation. METHODS: We defined a cohort of 1462 males who had been employed for at least 12 months between 1/11/1967 and 28/7/1995, followed-up through to 31/12/2001. The mortality of the cohort was compared against that expected for both national and regional populations. RESULTS: Mortality from all causes and all cancers did not differ from that expected. Mortality from ischaemic heart disease showed a deficit and mortality from lung cancer showed a statistically significant excess. Mortality from smoking related diseases other than lung cancer showed a non-significant deficit. CONCLUSIONS: The pattern of lung cancer mortality is consistent with the hypothesis that the risk of lung cancer has been enhanced by occupational exposure to one or more carcinogens, the effect of which diminishes with time since exposure. The deficit in ischaemic heart disease may be attributed to a protective effect from manual labour. The results provide no evidence for attribution of other excess or deficits in mortality to factors associated with employment.     

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.     

Mortality of workers at a plant manufacturing nickel alloys, 1958-2000

BACKGROUND: Excess risks of respiratory cancer have been demonstrated in some groups of nickel-exposed workers. It is clear, however, that not all forms of nickel exposure are implicated in these excess risks. Aim To determine whether occupational exposures received in the manufacture of nickel alloys lead to increased risks of cancer, in particular nasal cancer and lung cancer. METHODS: The mortality experienced by a cohort of 1999 workers employed at a plant manufacturing nickel alloys has been investigated. Study subjects were all those male workforce employees first employed in the period 1953-1992 who had at least 5 years employment with the company. Observed numbers of cause-specific deaths were compared with expectations based on national mortality rates. Standardized mortality ratios (SMRs) were calculated by period from commencing employment and by operating area of first job. In addition, rate ratios derived from Poisson regression and based on an internal standard were calculated by levels of duration of employment. RESULTS: SMRs were significantly below 100 for all causes (observed 557, expected 704.3, SMR 79), all neoplasms (observed 169, expected 209.4, SMR 81) non-malignant diseases of the respiratory system (observed 50, expected 73.0, SMR 69) and diseases of the circulatory system (observed 261, expected 335.5, SMR 78). Significantly elevated SMRs were not shown for any cause of death and mortality was below expectation for stomach cancer (observed 8, expected 16.0, SMR 50), lung cancer (observed 64, expected 73.6, SMR 87) and bladder cancer (observed 3, expected 8.0, SMR 38). There were no deaths from nasal cancer (expected 0.33). More detailed findings were unexceptional. CONCLUSIONS: The analyses did not suggest the presence of an occupational cancer hazard in the mortality experience of the cohort.     

Mortality pattern of silicotic subjects in the Latium region, Italy

A mortality study was carried out on 595 workers who were compensated for silicosis in the Latium region, Italy, during the period 1946-84 who died between 1 January 1969 and 31 December 1984. Respiratory disorders, tuberculosis, lung cancer, bone cancer, and cirrhosis of the liver showed significantly increased risk ratios (4.1, 3.7, 1.5, 4.1, and 1.9 respectively); excesses of brain cancer and leukaemia did not reach statistical significance. Lung cancer mortality was further analysed by age, period of compensation, final degree of disability, and occupational activity. The possible confounding role of smoking was assessed by comparing the lifetime smoking habits of a sample of silicotic subjects with those of the general male population as estimated by a national health survey; the prevalence of ever smokers among silicotic subjects (70.7%) was similar to that estimated for the general population (68.5%). The present study indicates that silicosis is associated with lung cancer even though it does not clarify the respective roles of exposure to silica and silicosis.     

Mortality pattern of silicotic subjects in the Latium region, Italy.

A mortality study was carried out on 595 workers who were compensated for silicosis in the Latium region, Italy, during the period 1946-84 who died between 1 January 1969 and 31 December 1984. Respiratory disorders, tuberculosis, lung cancer, bone cancer, and cirrhosis of the liver showed significantly increased risk ratios (4.1, 3.7, 1.5, 4.1, and 1.9 respectively); excesses of brain cancer and leukaemia did not reach statistical significance. Lung cancer mortality was further analysed by age, period of compensation, final degree of disability, and occupational activity. The possible confounding role of smoking was assessed by comparing the lifetime smoking habits of a sample of silicotic subjects with those of the general male population as estimated by a national health survey; the prevalence of ever smokers among silicotic subjects (70.7%) was similar to that estimated for the general population (68.5%). The present study indicates that silicosis is associated with lung cancer even though it does not clarify the respective roles of exposure to silica and 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.     

Retrospective mortality cohort study of Italian workers compensated for silicosis

Objectives

To estimate cause specific mortality in a large cohort of Italian workers compensated for silicosis.

Methods

The cohort included 14 929 subjects (14 098 men and 831 women) compensated for silicosis between 1946 and 1979, alive on 1 January 1980, and resident in Tuscany (a region of central Italy with 3 547 000 inhabitants). Mortality follow up ranged from 1980 to 1999. Vital status and the causes of death were determined by linkage with the regional mortality registry and with the national mortality database. The cohort mortality rates were compared to the rates of the local reference population. SMRs and their 95% confidence intervals were computed assuming a Poisson distribution of the observed deaths. Specific SMR analyses were performed according to the level of disability, the year of compensation assignment, and the job type.

Results

A significant excess mortality was observed in male silicotics for cancer of the lung, trachea, and bronchus and cancer of the liver, respiratory diseases (silicosis, asbestosis, antracosilicosis, and other pneumoconiosis), and for tubercolosis. Statistically significant mortality excess was observed in female silicotics for respiratory diseases (specifically silicosis and other pneumoconiosis) and tuberculosis. Analyses for period of compensation assignment showed a twofold increased SMR for biliary tract cancer among female workers and for liver cancer among male workers compensated before 1970.

Conclusions

The excess mortality from respiratory tract cancers and respiratory tract diseases detected in Italian compensated silicotics are in agreement with previous epidemiological studies. Although the twofold increased risk for liver cancer among males is suggestive of a possible association with silica dust exposure, the finding needs to be confirmed.     

Lung cancer mortality at a UK tin smelter

BACKGROUND: An earlier study of mortality among male former employees at a tin smelter in Humberside, UK, had identified excess mortality from lung cancer, which appeared to be associated with occupational exposure. AIMS: The aim of the present study was to investigate the relationship between lung cancer mortality and quantitative measures of exposure. METHODS: Using available records of occupational hygiene measurements, we established exposure matrices for arsenic, cadmium, lead, antimony and polonium-210 ((210)Po), covering the main process areas of the smelter. We established work histories from personnel record cards for the previously defined cohort of 1462 male employees. Three different methods of extrapolation were used to assess exposures prior to 1972, when no measurement results were available. Lung cancer mortality was examined in relation to cumulative inhalation exposure by Poisson regression analysis. RESULTS: No significant associations could be found between lung cancer mortality and simple cumulative exposure to any of the substances studied. When cumulative exposures were weighted according to time since exposure and attained age, significant associations were found between lung cancer mortality and exposures to arsenic, lead and antimony. CONCLUSIONS: The excess of lung cancer mortality in the cohort can most plausibly be explained if arsenic is the principal occupational carcinogen (for which the excess relative risk diminishes with time since exposure and attained age) and if there is a contribution to excess mortality from an enhanced prevalence of smoking within the cohort. The implications of the dose-response for arsenic exposure for risk estimation merit further consideration.     

Mortality study among workers producing ferroalloys and stainless steel in France.

A mortality study was carried out among the workers of a plant that had produced ferrochromium and stainless steel, and was still producing stainless steel, in order to determine whether exposure to chromium compounds, to nickel compounds, and to polycyclic aromatic hydrocarbons (PAH) could result in a risk of lung cancer for the exposed workers. The cohort comprised 2269 men whose vital status were recorded between 1 January 1952 and 31 December 1982. The smoking habits of 67% of the cohort members were known from medical records. The observed numbers of deaths were compared with the expected ones based on national rates with adjustment for age, sex, and calendar time. A low mortality, achieving statistical significance, was found from all causes (observed = 137, standardised mortality ratio (SMR) = 0.82) and from benign respiratory diseases (observed = one, SMR = 0.15). With regard to mortality from lung cancer, a non-significant excess appeared in the whole cohort (observed = 12, SMR = 1.40). Among the exposed workers, however, a significant lung cancer excess was found (observed = 11, SMR = 2.04) that contrasted with a low SMR (0.32) in the non-exposed group. This excess is unlikely to be explained by smoking, as the tobacco consumption of these two groups was similar. No trend was observed for mortality from lung cancer either according to time since first exposure, or according to duration of exposure. A nested case-control study clearly suggested that this excess of deaths from lung cancer was attributable to former PAH exposures in the ferrochromium production workshops rather than to exposures in the stainless steel manufacturing areas.     

Mortality study among workers producing ferroalloys and stainless steel in France

A mortality study was carried out among the workers of a plant that had produced ferrochromium and stainless steel, and was still producing stainless steel, in order to determine whether exposure to chromium compounds, to nickel compounds, and to polycyclic aromatic hydrocarbons (PAH) could result in a risk of lung cancer for the exposed workers. The cohort comprised 2269 men whose vital status were recorded between 1 January 1952 and 31 December 1982. The smoking habits of 67% of the cohort members were known from medical records. The observed numbers of deaths were compared with the expected ones based on national rates with adjustment for age, sex, and calendar time. A low mortality, achieving statistical significance, was found from all causes (observed = 137, standardised mortality ratio (SMR) = 0.82) and from benign respiratory diseases (observed = one, SMR = 0.15). With regard to mortality from lung cancer, a non-significant excess appeared in the whole cohort (observed = 12, SMR = 1.40). Among the exposed workers, however, a significant lung cancer excess was found (observed = 11, SMR = 2.04) that contrasted with a low SMR (0.32) in the non-exposed group. This excess is unlikely to be explained by smoking, as the tobacco consumption of these two groups was similar. No trend was observed for mortality from lung cancer either according to time since first exposure, or according to duration of exposure. A nested case-control study clearly suggested that this excess of deaths from lung cancer was attributable to former PAH exposures in the ferrochromium production workshops rather than to exposures in the stainless steel manufacturing areas.     

Lung cancer in the meat industry

Routine statistics of occupational mortality and incidence of cancer have consistently shown high rates of lung cancer in butchers. Possible explanations include infection by carcinogenic papilloma viruses, exposure to polycyclic aromatic hydrocarbons and nitrites in the preservation of meat, or a confounding effect of tobacco. To explore these possibilities, we have examined the mortality of 1610 men employed at three British companies processing pork, beef, lamb, bacon, and other meat products. The overall death rate was less than in the national population (271 deaths observed, 310 expected) but there was an excess of deaths from cancer (87 observed, 80 expected), and in particular from lung cancer (42 observed, 32 expected). The risk of lung cancer was concentrated in subjects exposed to recently slaughtered meat, especially after an interval of 10 or more years. These findings increase suspicions of a risk of lung cancer in butchers, although further information is needed about smoking habits in the meat industry. If there is a hazard infection by a papilloma virus would seem the most likely cause.     

Lung cancer in the meat industry.

Routine statistics of occupational mortality and incidence of cancer have consistently shown high rates of lung cancer in butchers. Possible explanations include infection by carcinogenic papilloma viruses, exposure to polycyclic aromatic hydrocarbons and nitrites in the preservation of meat, or a confounding effect of tobacco. To explore these possibilities, we have examined the mortality of 1610 men employed at three British companies processing pork, beef, lamb, bacon, and other meat products. The overall death rate was less than in the national population (271 deaths observed, 310 expected) but there was an excess of deaths from cancer (87 observed, 80 expected), and in particular from lung cancer (42 observed, 32 expected). The risk of lung cancer was concentrated in subjects exposed to recently slaughtered meat, especially after an interval of 10 or more years. These findings increase suspicions of a risk of lung cancer in butchers, although further information is needed about smoking habits in the meat industry. If there is a hazard infection by a papilloma virus would seem the most likely cause.     

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.     

Mortality and incidence of cancer among Swedish gas workers.

The mortality and incidence of cancer was studied among 295 workers at a Swedish gas production company. All men employed for at least one year between 1965 and 1972 were included in the study. The follow up period for mortality was 1966 to 1986, and the incidence of cancer was followed up from 1966 to 1983. Expected numbers of deaths were based on local death rates among occupationally active men, the expected numbers of cancer were based on national statistics. The total mortality was increased, mainly due to an excess of deaths from circulatory diseases. The excess was larger after long follow up and after long employment periods. Two cases of cancer in the nose and nasal sinuses were found; there was no excess of lung cancer. Smoking habits were investigated for a subset of the cohort and did not differ from the average for men in large cities. The findings are discussed in relation to other studies of soot and combustion exposed workers.     

Mortality and incidence of cancer among Swedish gas workers

The mortality and incidence of cancer was studied among 295 workers at a Swedish gas production company. All men employed for at least one year between 1965 and 1972 were included in the study. The follow up period for mortality was 1966 to 1986, and the incidence of cancer was followed up from 1966 to 1983. Expected numbers of deaths were based on local death rates among occupationally active men, the expected numbers of cancer were based on national statistics. The total mortality was increased, mainly due to an excess of deaths from circulatory diseases. The excess was larger after long follow up and after long employment periods. Two cases of cancer in the nose and nasal sinuses were found; there was no excess of lung cancer. Smoking habits were investigated for a subset of the cohort and did not differ from the average for men in large cities. The findings are discussed in relation to other studies of soot and combustion exposed workers.