Standardized Mortality Ratio For Lung Cancer Research Articles

Mortality of a cohort of French uranium miners exposed to relatively low radon concentrations

A cohort mortality study has been performed on French uranium miners having experienced more than 2 years of underground mining, with first radon exposure between 1946 and 1972. Vital status has been ascertained from the date of entry to the 31 December 1985 for 99% of the members of this cohort; causes of death are identified for 95.5% of the decedents. The different causes of death are compared to the age specific national death rates by indirect standardisation and expressed by standardised mortality ratios (SMR). A statistically significant excess has been observed for lung and laryngeal cancer deaths. The Poisson trend test shows a statistically significant trend for the risk of lung cancer death as a function of cumulative radon exposure, assuming a lag time of 5 years; for laryngeal cancer no significant trend has been observed. Poisson regression modelling has been applied to the following exposure groups: < 10 WLM (Working Level Month); 10-49 WLM; 50-149 WLM; 150-299 WLM; > or = 300 WLM; it indicates an increase in the SMR for lung cancer of 0.6% per WLM (standard error: 0.4%) with an estimated intercept at 0 WLM of 1.68 (standard error: 0.4). The distinction of two working periods, differing by their annual radon concentration (before/since 1956) does not modify this exposure-response relationship. This coefficient of risk per unit of exposure is lower than in most of the other uranium miners' studies but it lies in the range of the evaluation of the ICRP 50 committee and the 'BEIR IV' report of the U.S. National Academy of Science. It is observed in a cohort having experienced low cumulative exposure to radon (mean: 70 WLM) spread over a mean duration of 14.5 years. Even though occupational exposure in mines differs in several particulars from domestic exposure, this study presents characteristics of low annual exposure comparable to radon gas concentrations in houses of 500-1000 Bq.m-3, and will contribute to the evaluation of cancer risk for the public.

A mortality study among mild steel and stainless steel welders.

A mortality study was carried out in conjunction with the European mortality study among welders coordinated by the International Agency for Research on Cancer (IARC). The study was aimed at assessing risks for lung cancer in relation to exposure to asbestos, welding fumes containing chromium and nickel, and tobacco smoke. The study included a cohort of 2721 welders and an internal comparison group of 6683 manual workers employed in 13 factories in France. The mortality of the two cohorts was studied from 1975 to 1988 by the historical prospective method. Job histories of welders were traced including welding processes used, metals welded, and proportion of worktime spent in welding. Data on smoking habits were collected from medical records. The observed number of deaths were compared with those expected (standardised mortality ratio (SMR)) based on national rates with adjustments for age, sex, and calendar time. The smoking habits of 87% of the whole study population were known. The distribution of welders and controls according to smoking was not statistically different. The overall mortality was slightly higher for welders (SMR = 1.02, 95% confidence interval (95% CI) 0.89-1.18) than for controls (SMR = 0.91, 95% CI 0.84-0.99). For lung cancer, the SMR was 1.24 (95% CI 0.75-1.94) for welders, whereas the corresponding value was lower for controls (SMR = 0.94, 95% CI 0.68-1.26). The SMR for lung cancer was 1.59 among non-shipyard mild steel welders (95% CI 0.73-3.02). This contrasted with the results for all stainless steel welders (SMR = 0.92, 95% CI 0.19-2.69), and for stainless steel welders predominantly exposed to chromium VI (SMR = 1.03, 95% CI 0.12-3.71). Moreover, SMRs for lung cancer for mild steel welders tended to increase with duration of exposure and time since first exposure, leading to significant excesses for duration > or = 20 years and latency > or = 20 years. Such a pattern was not found for stainless steel welders.

A mortality study of cobalt production workers: an extension of the follow-up.

The follow-up of a cohort of workers employed in an electrochemical plant producing cobalt and sodium, previously studied from 1950-1980, has been extended from 1981-1988. The standardized mortality ratio (SMR) for all causes of death was 0.85 (95% confidence interval [CI] = 0.76-0.95, 309 observed) for the whole cohort, and 0.95 (95% CI = 0.83-1.08, 247 observed) for the subcohort of workers born in France. With regard to lung cancer mortality among cobalt production workers, which is the main objective of the study, the SMRs were, respectively, 0.85 (95% CI = 0.18-2.50, 3 observed) and 1.16 (95% CI = 0.24-3.40, 3 observed). Neither did any excess of mortality from diseases of the circulatory and of the respiratory systems appear among cobalt production workers. Maintenance workers, however, exhibited high SMRs for lung cancer, reaching statistical significance for duration of exposure and time since first exposure > or 30 years. This study does not support the hypothesis of a relationship between lung cancer and cobalt exposure.

A mortality study of workers at seven beryllium processing plants.

The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01-1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21-1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis.

Lung Cancer Incidence Among Patients With Beryllium Disease: A Cohort Mortality Study

We have conducted a cohort mortality study on 689 patients with beryllium disease who were included in a case registry. An earlier mortality study on 421 of these patients was limited to males and resulted in a determination of a nonsignificant twofold lung cancer excess based on only seven lung cancer deaths. We have extended this earlier study by including females and by adding 13 years of follow-up. Comparison of the 689 beryllium disease patients with the U.S. population resulted in a lung cancer standardized mortality ratio (SMR) of 2.00 (95% confidence interval = 1.33-2.89) based on 28 observed lung cancer deaths. Adjustment for smoking did not change these results. All causes of mortality were also significantly elevated (SMR = 2.19), largely because of the very high rate of deaths due to pneumoconioses (primarily beryllium disease) (SMR = 34.23; 158 deaths). No other causes of death were significantly elevated. The excess of lung cancer was consistent for both sexes and did not appear to increase with duration of exposure to beryllium or with time elapsed since first exposure to this element. The case registry included those with acute beryllium disease, which resembles a chemical pneumonitis, and those with chronic beryllium disease, which resembles other pneumoconioses. The lung cancer excess was more pronounced among those with acute disease (SMR = 2.32) than among those with chronic disease (SMR = 1.57).

Mortality of 11,500 Nickel Workers—Extended Follow Up and Relationship to Environmental Conditions

An extended follow-up from 1977-84 was achieved in a cohort of 11,567 nickel workers engaged in mining, milling and smelting originally studied from 1950-76. Exposure data were incorporated into the analysis. One nasal cancer occurred. The lung cancer Standardized Mortality Ratio beyond 15 years from first exposure was significantly high overall (128) and in miners (153). However, detailed analyses by era of first mining and duration of mining, as well as cumulative exposure to different nickel species, did not appear consistent with an occupational etiology since significant trends were not observed. At the levels of exposure incurred, large increases in lung and nasal cancer, observed in nickel refineries elsewhere, did not occur.

Mortality of a cohort of tin miners 1941-86.

The mortality patterns of United Kingdom tin miners were examined in relation to calendar period and duration of underground work with particular attention to lung cancer and exposure to radon. Subjects were all men who had worked for at least one year between 1941 and 1984 at one of two United Kingdom tin mines and for whom a complete work history could be constructed from mine records. Standardised mortality ratios (SMRs) were calculated using national (England and Wales) rates. The pattern of SMRs in relation to potential explanatory variables was analysed using Poisson regression methods. Mortalities from lung cancer and silicosis (including silicotuberculosis) were significantly raised and showed a significant relation with duration of underground work (mortality from stomach cancer was raised in both underground and surface workers, but not significantly). Excess mortality from silica related disease declined steeply from 35% among workers first exposed before 1920 to 1% among those first exposed after 1950. Thirteen surface workers with known exposure to arsenic had high rates of lung and stomach cancer. The SMR for lung cancer showed a consistent pattern in relation to duration of underground exposure, rising from 83 (observed/expected = 8/9.6) for surface workers (without exposure to arsenic) to 447 (15/3.4) for workers with more than 30 years underground exposure. Examination of the SMR for lung cancer by total underground exposure, age, and time since last exposure gave rise to a model for the expression of risk which depends only on total exposure and time since exposure. The fitted model implies that the effect of exposure to radon in a given year has no effect on risk for 10 years, then rapidly rises to a maximum from which the excess risk then declines, halving every 4.3 years. There were no direct measurements of historic radon levels. A conservative estimate based on measurements taken since 1969 by the National Radiological Protection Board and the Mines and Quarries Inspectorate is that the annual dose to an underground worker was about 10 working level months (WLM). Given this assumption, the risk/exposure slope implied by the present data, and the model fitted to it, was somewhat lower than that given in the fourth Committee on the Biological Effects of Ionisation Radiation (BEIR IV) report (about 40% lower for lifetime exposures). The present data also imply different risks depending on the age at exposure, with relatively higher lifetime risks for exposure at older ages, and relatively lower risks for exposures at younger ages. In conclusion, there was a clear relation between exposure to radon and death from lung cancer. The relative risk of lung cancer due to exposure to radon was not constant in cessation of exposure. The lifetime excess risk of lung cancer implied by these data for 40 years exposure at the current statutory limit of four WLM a year starting at age 20, was about 8% (79 excess deaths per 1000 exposed), assuming average smoking habits among the exposed workers. Control of dust concentrations in the mines has substantially reduced--and may have eliminated--direct mortality from silica related disease.

Epidemiological Study of Mortality from Cancer Among Chromium Platers

Cancer mortality was studied among 265 male workers in 40 small plating factories (chromium, copper and nickel) where bicycle parts are plated. The study utilized record linkage with the Osaka Cancer Registry file between January 1, 1965 and December 31, 1979. The results showed that seven workers had died of cancer, and the Standardized Mortality Ratio (SMR) calculated for all cancers, stomach cancer and lung cancer were 1.13, 1.23 and 1.11, respectively, with no significant relationship found between the observed and expected values. The SMR for lung cancer among those workers with a high degree of skin ulceration and with perforation of the nasal septum was high, 11.22 and 5.13, respectively, although not statistically significant because of the small sample size in the study. The results suggest that lung cancer occurs in those subjected to a high degree of exposure to chromium.

Retrospective Cohort Mortality Study of Roman Catholic Priests

In order to test the hypothesis that Roman Catholic priests are at low risk for prostatic cancer because of their celibacy, a cohort of 10,026 men who were active or retired diocesan (parish) Roman Catholic priests in the United States on January 1, 1949 were followed until death, leaving the priesthood, or January 1, 1978. The overall standardized mortality ratio (SMR) was 103 and the SMR for cancer of the prostate was 81. Other interesting findings include increased SMRs for cancer of the larynx (147), cirrhosis of the liver (147), and diabetes (182) and decreased SMRs for lung cancer (59), emphysema (26), and suicide (13).

Retrospective cohort mortality study of Roman Catholic Priests

In order to test the hypothesis that Roman Catholic priests are at low risk for prostatic cancer because of their celibacy, a cohort of 10,026 men who were active or retired diocesan (parish) Roman Catholic priests in the United States on January 1, 1949 were followed until death, leaving the priesthood, or January 1, 1978. The overall standardized mortality ratio (SMR) was 103 and the SMR for cancer of the prostate was 81. Other interesting findings include increased SMRs for cancer of the larynx (147), cirrhosis of the liver (147), and diabetes (182) and decreased SMRs for lung cancer (59), emphysema (26), and suicide (13).

A second follow-up of mortality in a cohort of pesticide applicators.

A cohort of 16,124 male pesticide applicators was matched with Social Security Administration and National Death Index (NDI) files through December 31, 1984. In all, 1,082 deaths were ascertained, and death certificates were obtained for 994 (92%). The standardized mortality ratio (SMR) for all causes of death was 98. Although a number of specific causes of death showed SMRs significantly below 100, only one category of cause of death showed a significantly elevated SMR--cancer of the lung, with an SMR of 135. Termite control operators (TCO)--the group with the greatest likelihood of exposure to chlordane and heptachlor--had an SMR for lung cancer of 97, compared with 158 for other pesticide operators. The excess of lung cancer in the non-TCO workers was limited to operators employed as such for less than five years.

Asbestos exposure and gastrointestinal malignancy review and meta-analysis.

The epidemiologic literature linking asbestos exposure with gastrointestinal malignancy is reviewed. Problems in comparing studies are discussed, appropriate strategies for comparison are developed, and study results are pooled using a model which accounts for both intrastudy and interstudy variability. Stratification of cohorts by dose reveals that significant asbestos exposure, as indicated by a lung cancer standardized mortality ratio (SMR) of at least 200, is associated with an elevated gastrointestinal cancer of SMR for five of six points examined [corrected].

Mortality from lung cancer and respiratory disease among pottery workers exposed to silica and talc.

A cohort mortality study of white men employed for at least one year between 1939 and 1966 at three plants of a single United States company was conducted to evaluate the risk of lung cancer and nonmalignant respiratory disease among workers exposed to silica dust and nonfibrous (nonasbestiform) talc in the manufacture of ceramic plumbing fixtures. Follow-up of 2,055 men through January 1, 1981, indicated a substantial excess of nonmalignant respiratory disease among those with high levels of exposure to silica dust (standardized mortality ratio = 2.26). The risk of nonmalignant respiratory disease rose with the number of years exposed, was not further enhanced by talc exposure, and appeared to be appreciably lower among those exposed in more recent time periods. For lung cancer, men exposed to high levels of silica dust with no talc exposure had a nonsignificant standardized mortality ratio of 1.37. However, those exposed to nonfibrous talc in addition to high levels of silica had a significant 2.5-fold excess risk of lung cancer. Among this group, the lung cancer standardized mortality ratio rose with increasing years of talc exposure to 3.64 among those exposed for 15 or more years. Although the role of silica as a cofactor cannot be ruled out, these data suggest that nonfibrous talc exposure is associated with excess lung cancer risk.

Mortality and lead exposure: a retrospective cohort study of Swedish smelter workers.

The study is based on the work histories and mortality data for 3832 male workers first employed before 1967 at a copper smelter in northern Sweden and followed up from 1950 to 1981. From the 3832 workers a lead cohort consisting of 437 workers employed for at least three years at sites with considerable lead exposure during 1950-74 was selected. These workers had regularly had blood lead measurements performed since 1950. Based on the cumulative blood lead dose 1950-74 and peak blood lead values, the cohort was subdivided into high mean, low mean, high peak, and low peak groups. Standardised mortality ratios (SMR) were calculated for the six groups using general and local reference populations. The original cohort of 3832 workers showed considerable excess of deaths for total mortality, malignant neoplasms especially lung and stomach cancer, ischaemic heart diseases, and cerebrovascular diseases when compared with the general population. In the lead cohort where the workers had been subjected to a considerable lead exposure only the raised SMR for lung cancer was sustained (SMR = 162; not significant). No significant differences were found between high lead and low lead exposed smelter workers.

The use of regression analyses in a cohort mortality study of welders

Using an internal nonexposed comparison group, and two types of regression analysis, we have reanalyzed the data from a cohort mortality study of 3247 welders and 5432 nonwelders who worked in Western Washington during the period 1950–1976. Previous analyses relied primarily on the standardized mortality ratio (SMR) for lung cancer as a summary statistic to estimate relative risk; welders were compared to the U.S. population, stratified by age, sex, race, and calendar time. In the present study, nonwelders from the same union were used as the reference group; an internal referent group is often preferable to the U.S. population because it is likely to have shared similar lifestyles (e.g. smoking habits) as the exposed. Cox regression was used to estimate relative risk. In addition, the data was analyzed via logistic regression in order to compare Cox to logistic regression. A regression analysis of these data enabled us to analyze exposure as a continuous variable and simultaneously adjust for potentially confounding variables without stratification. Interactions terms could also be easily tested. The previous analysis found as SMR for lung cancer of 1.32 ( p = 0.06). Cox regression with an internal comparison group yielded similar results. Issues discussed include the differences between logistic and Cox regression, the appropriate variable for time in Cox regression, and the definition of risk set in Cox regression. Finally, a newly available program is discussed which selects random samples of the risk sets used in Cox regression, in order to do a case-control analysis.

Relations between asbestos exposure and lung cancer SMRs in occupational cohort studies.

It has long been accepted that excessive exposure to asbestos may produce lung cancer but not that there is a consistent "biological gradient." This can only be evaluated reliably in studies where, for every individual, exposure has been measured in terms of both duration and intensity. Even now, there are only at most eight such cohort studies of asbestos workers, while femoral methods of analysis have been available only recently. These methods, applied in these studies, yield good evidence that the "exposure-response" relation between accumulated exposure to asbestos and standardised mortality ratios (SMRs) for lung cancer may be taken as linear, but that at zero exposure the lung cancer SMR is not always unity--not surprising, because of well known difficulties with the choice of reference population and selection problems. This leads to a concept of "relative slopes" that take account of the background mortality in the cohort and make what appears to be the best use of the available data. Other approaches to the same data, and indeed to all cohort data known, are also considered. Each study is examined as closely as is possible in a short review, and the concepts of linearity and relative slopes appear justified. The relative slopes (b/a) in the line SMR = a[1 + (b/a) . (exposure)] vary much more widely than can be accounted for by differences in epidemiological methodology; as discussed elsewhere, reasons for the variation seem to lie rather in type and dimensions of asbestos fibre, industrial process, etc. Slopes in the line SMR = 1 + b1 . (exposure) vary about twice as much as do the relative slopes.

Mortality rates for farmers and fishermen in Japan compared with England and Wales

Life tables for all causes of death for farmers and fisherman in Japan have been compared with those for England and Wales. Considering all causes of death, there are no occupational differences between farmers and fishermen in Japan. On the other hand, there are large occupational differences indicating that fishermen are worse off than farmers in England and Wales. Standardized mortality ratios (SMR) for each disease in terms of occupation have also been compared in the two countries. The SMRs for leading causes of death in Japan, such as cerebrovascular disease, are significantly lower for fishermen than for farmers in Japan. On the contrary, SMRs for leading causes of death in England and Wales, such as ischemic heart disease and lung cancer, are significantly higher for fishermen than for farmers in England and Wales. However the SMRs for ischemic heart disease and lung cancer are significantly higher for fishermen than for farmers in both countries.

Mortality study of British pathologists 1974-80.

Membership lists of the Royal College of Pathologists from 1974 to 1980 were used to establish a population of 2307 men and 413 women. During the period of study 126 of these pathologists died and death certificates were obtained for 121. The standardised mortality ratios (SMR) for all causes in men were 56 and in women 99. Deaths from accidents, poisoning, violence, and especially suicide, were noted to be in excess of that expected from the general population but similar to that for medical practitioners. Drug overdose was the cause of each suicide. Excess deaths from lymphatic and haemopoietic neoplasms noted in a previous study were not present but an excess of brain tumours was found. Including 1981 data thus far collected, deaths from brain tumour were apparently in excess (observed 6, expected less than 2.0, p less than 0.02). Possible aetiological hypotheses include previous exposure to organic solvents or tuberculosis infection. In view of the pathologists' exposure to formaldehyde it is interesting to note that no nasal or nasal sinus tumours were reported and the SMR for lung cancer was 41.

Mortality Among Male Workers at a Thorium-processing Plant

The long-term health effects of exposure to thorium are of interest because of the possible increased use of thorium as an energy source in reactors using 232Th to produce 233U. Mortality is described in a cohort of 3039 men who were employed between 1940 and 1973 at a company involved in the production of thorium and rare earth chemicals from monazite sand. Based on deaths ascertained by the Social Security Administration and mortality rates for U.S. white males, the standardized mortality ratio (SMR) for all causes was 1.05 with 95% confidence limits (95% CL) of 0.96 and 1.15. Much of the excess mortality was attributable to non-occupational motor vehicle accidents (SMR = 1.64; 95% CL = 1.16 and 2.23), but SMRs were also high for lung cancer (1.44; 95% CL = 0.98 and 2.02), pancreatic cancer (2.01; 95% CL = 0.92 and 3.82), and diseases of the respiratory system (1.31; 95% CL=0.92 and 1.83). In a subgroup of 592 men who worked for at least one year in selected jobs (indicative of highest exposure to thorium and thoron) that was followed up more intensively, the SMR for pancreatic cancer was significantly elevated (i.e. 4.13; 95% confidence limits = 1.34 and 9.63). The SMR for lung cancer was 1.68 (95% CL = 0.81 and 3.09), while that for respiratory diseases was 1.20 (95% CL = 0.52 and 2.37). Information on smoking habits in a sample of survivors suggested that smoking could have explained at least part of the excess mortality from lung and pancreatic cancer and from diseases of the respiratory system. Continued follow-up of the cohort through morbidity and mortality studies is needed to evaluate further the possible long-term effects of exposure to radioactivity and chemicals in the thorium extraction process.

Mortality Among Male Workers at a Thorium-processing Plant

The long-term health effects of exposure to thorium are of interest because of the possible increased use of thorium as an energy source in reactors using 232Th to produce 233U. Mortality is described in a cohort of 3039 men who were employed between 1940 and 1973 at a company involved in the production of thorium and rare earth chemicals from monazite sand. Based on deaths ascertained by the Social Security Administration and mortality rates for U.S. white males, the standardized mortality ratio (SMR) for all causes was 1.05 with 95% confidence limits (95% CL) of 0.96 and 1.15. Much of the excess mortality was attributable to non-occupational motor vehicle accidents (SMR = 1.64; 95% CL = 1.16 and 2.23), but SMRs were also high for lung cancer (1.44; 95% CL = 0.98 and 2.02), pancreatic cancer (2.01; 95% CL = 0.92 and 3.82), and diseases of the respiratory system (1.31; 95% CL=0.92 and 1.83). In a subgroup of 592 men who worked for at least one year in selected jobs (indicative of highest exposure to thorium and thoron) that was followed up more intensively, the SMR for pancreatic cancer was significantly elevated (i.e. 4.13; 95% confidence limits = 1.34 and 9.63). The SMR for lung cancer was 1.68 (95% CL = 0.81 and 3.09), while that for respiratory diseases was 1.20 (95% CL = 0.52 and 2.37). Information on smoking habits in a sample of survivors suggested that smoking could have explained at least part of the excess mortality from lung and pancreatic cancer and from diseases of the respiratory system. Continued follow-up of the cohort through morbidity and mortality studies is needed to evaluate further the possible long-term effects of exposure to radioactivity and chemicals in the thorium extraction process.