Radon and cancers other than lung cancer in underground miners: a collaborative analysis of 11 studies.

BACKGROUND: Exposure to the radioactive gas radon and its progeny (222Rn and its radioactive decay products) has recently been linked to a variety of cancers other than lung cancer in geographic correlation studies of domestic radon exposure and in individual cohorts of occupationally exposed miners. PURPOSE: This study was designed to characterize further the risks for cancers other than lung cancer (i.e., non-lung cancers) from atmospheric radon. METHODS: Mortality from non-lung cancer was examined in a collaborative analysis of data from 11 cohorts of underground miners in which radon-related excesses of lung cancer had been established. The study included 64,209 men who were employed in the mines for 6.4 years on average, received average cumulative exposures of 155 working-level months (WLM), and were followed for 16.9 years on average. RESULTS: For all non-lung cancers combined, mortality was close to that expected from mortality rates in the areas surrounding the mines (ratio of observed to expected deaths [O/E] = 1.01; 95% confidence interval [CI] = 0.95-1.07, based on 1179 deaths), and mortality did not increase with increasing cumulative exposure. Among 28 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (O/E = 1.33; 95% CI = 1.16-1.52) and liver (O/E = 1.73; 95% CI = 1.29-2.28) and statistically significant decreases for cancers of the tongue and mouth (O/E = 0.52; 95% CI = 0.26-0.93), pharynx (O/E = 0.35; 95% CI = 0.16-0.66), and colon (O/E = 0.77; 95% CI = 0.63-0.95) were observed. For leukemia, mortality was increased in the period less than 10 years since starting work (O/E = 1.93; 95% CI = 1.19-2.95) but not subsequently. For none of these diseases was mortality significantly related to cumulative exposure. Among the remaining individual categories of non-lung cancer, mortality was related to cumulative exposure only for cancer of the pancreas (excess relative risk per WLM = 0.07%; 95% CI = 0.01-0.12) and, in the period less than 10 years since the start of employment, for other and unspecified cancers (excess relative risk per WLM = 0.22%; 95% CI = 0.08-0.37). CONCLUSIONS: The increases in mortality from stomach and liver cancers and leukemia are unlikely to have been caused by radon, since they are unrelated to cumulative exposure. The association between cumulative exposure and pancreatic cancer seems likely to be a chance finding, while the association between cumulative exposure and other and unspecified cancers was caused by deaths certified as due to carcinomatosis (widespread disseminated cancer throughout the body) that were likely to have been due to lung cancers. This study, therefore, provides considerable evidence that high concentrations of radon in air do not cause a material risk of mortality from cancers other than lung cancer. IMPLICATIONS: Protection standards for radon should continue to be based on consideration of the lung cancer risk alone.

Lung cancer in radon-exposed miners and estimation of risk from indoor exposure.

BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners.

Estimating lung cancer mortality from residential radon using data for low exposures of miners.

Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures.

Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects.

Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

Hospital records: an underutilized source of information regarding occupational diseases and exposures.

A 1993 study examined the association between pneumoconiosis and cor pulmonale using a computerized data base of hospital records in Ontario (Hospital Medical Records Institute, HMRI). The present investigation was undertaken to confirm the coding of the diagnoses of a subset of the hospital discharges from that study, to determine the validity of the coding of the diagnoses of coal workers' pneumoconiosis (CWP), and to identify work exposure (occupation and industry) information available in hospital records. We sent abstraction forms to hospitals for 521 subjects who were hospitalized for pneumoconiosis, cor pulmonale, or both conditions, requesting information regarding diagnoses, occupation and industry data, and X-ray results. Abstracts were received for 720 (76%) of 944 discharges that were sought. The hospital abstractions confirmed the HMRI coding for 90% of the charts with these conditions, including 63%, 97%, and 96% discharges for CWP, silicosis, and asbestosis, respectively. Specific dust exposures were indicated in 42% of the charts with a code indicating a diagnosis of CWP, and of these, 67% indicated exposure to coal dust. Of charts with a code indicating a diagnosis of silicosis, 73% with specific dust information indicated silica exposure, and 95% of those for asbestosis indicated exposure to asbestos. Of 34 individuals in this data set known from the Ministry of Labour's Chest Clinic X-ray Surveillance Program of miners to have silicosis, 33 (97%) were diagnosed by the hospitals as having pneumoconiosis, and all but two were silicosis. Hospital records, as reflected by HMRI data, are reliable indicators of cor pulmonale and pneumoconiosis. The agreement with the Chest Clinic's X-ray diagnoses provides additional objective confirmation of the accuracy of the hospital information. There were relatively few cases of silicosis miscoded as CWP. At least for pneumoconioses, hospital records contained information about the exposures that led to these diseases in approximately 50% of the cases. However, whether hospital records would prove useful for detecting other work-related conditions that are not pathognomonic of occupation is not known. The importance of taking occupational histories needs continued emphasis in medical education and training.

Musculoskeletal problems among Ontario dental hygienists.

Two U.S. surveys suggested that dental hygienists (DHs) may suffer from carpal tunnel syndrome (CTS), but these studies did not use validated questionnaires, adjust for confounders, or include external controls. We conducted a questionnaire survey of all 2,142 DHs belonging to the Ontario Dental Hygienists' Association, and a referent group of 305 dental assistants (DAs), who do not scale teeth. The Standardized Nordic Questionnaire was used as the basis for asking about musculoskeletal symptoms. The response rates in the two groups were identical. Of the DHs, 7.0% had been told by a physician since starting work that they had CTS, but only 1 of 65 had received workers' compensation. Compared to the DAs, after adjusting for age the DHs were 5.2 times (95% confidence interval [CI] 0.9-32) more likely to have been told they had CTS and 3.7 times (95% CI 1.1-11.9) more likely to meet a CTS case definition. The DHs were also 2.5 (95% CI 1.6-3.9), 2.8 (95% CI 1.8-4.4), and 1.8 (95% CI 1.2-2.7) times more likely to report hand/wrist, shoulder, and neck problems in the past 12 months, respectively, but were less likely to report low back trouble. In internal analyses among DHs using logistic regression models, the number of heavy calculus patients per day, "clock" position around the dental chair, and years in practice were significant predictors of CTS. Days worked per week (but not heavy calculus patients), time with the trunk rotated, and years of practice were significant predictors of reported shoulder trouble in the past 12 months. Given that there are more than 9,000 DHs in Canada and about 100,000 in the United States, these findings suggest an important public health problem. They highlight the need to inform DHs during training and continuing education about musculoskeletal problems in general and CTS in particular. Attention should be directed to areas such as work station design, posture, treating patients with heavy calculus, and scheduling rest periods.

Mortality from lung cancer in Ontario uranium miners.

Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardised mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men. Smoking does not explain the whole excess. Mortality from lung cancer in Ontario uranium miners is clearly related to exposure to short lived radon progeny. The excess relative risk of lung cancer from the same degree of exposure to short lived radon progeny is greatest five to 14 years after exposure and less subsequently. It is greater in men under the age of 55 years and less in older men. Part of the excess of lung cancer mortality in Ontario uranium miners is probably also due to exposure to arsenic that occurred earlier in gold mines. In Ontario uranium miners, the lung cancer mortality from exposure to arsenic increases as the intensity of exposure to short lived radon progeny increases. This finding is consistent with the hypothesis that the risk of lung cancer from exposure to arsenic is enhanced by exposure to other carcinogens. In Ontario uranium miners, the proportion of lung cancers that are small cell carcinomas is greater than in the general population. The proportion of small cell carcinomas is especially great five to 14 years after exposure to short lived radon progeny and in men who die from lung cancer at younger ages.

Mortality from stomach cancer in Ontario miners.

An excess of mortality from stomach cancer has been found in Ontario gold miners (observed (obs) 104, standardised mortality ratio (SMR) 152, 95% confidence interval (95% CI) 125-185) and no excess of stomach cancer could be detected in other miners in Ontario (obs 74, SMR 102, 95% CI 80-128). The excess of stomach cancer appeared five to 19 years after the miners began gold mining in Ontario. In that interval, similar patterns of excess mortality from stomach cancer were found in miners born in north America (obs 14, SMR 268, CI 147-450) and in miners born outside north America (obs 12, SMR 280, 95% CI 145-489). Twenty or more years after the miners began mining gold, an excess of mortality from stomach cancer was found in gold miners born outside of north American (obs 41, SMR 160, 95% CI 115-218) but not in gold miners born in north America (obs 37, SMR 113, 95% CI 80-156). The excess of stomach cancer in gold miners under the age of 60 (obs 45, SMR 167, 95% CI 122-223) seems larger than the excess in gold miners between the ages of 60 and 74 (obs 59, SMR 143, 95% CI 109-184). Exposures to arsenic, chromium, mineral fibre, diesel emissions, and aluminium powder were considered as possible explanations of the excess of stomach cancer in Ontario gold miners. Exposure to diesel emissions and aluminium powder was rejected as gold miners and uranium miners were exposed to both agents but an excess of stomach cancer was noted only in gold miners. The association between the excess of stomach cancer and the time since the miner began mining gold suggested that duration of exposure to dust in gold mines ought to be weighted according to the time since the exposure to dust occurred and that an appropriate time weighting function would be one in the interval five to 19 years after each year of exposure to dust and zero otherwise. A statistically significant association between the relative risk of mortality from stomach cancer and the time weighted duration of exposure to dust in gold mines was found in miners under the age of 60. Time weighted indices of exposure to chromium and arsenic were formed for each gold miner by time weighting the product of the duration of exposure to dust in a gold mine and the percentages of arsenic and chromium in rocks in that gold mine. Exposure to mineral fibre was measured in terms of the time weighted duration of employment in those gold mines that contain mineral fibre. A statistically significant association between the excess of stomach cancer in gold miners under the age of 60 and the time weighted index of exposure to chromium occurred and not association was found between the excess of stomach cancer and either the time weighted duration of employment in mines containing mineral fibre. The excess of stomach cancer in gold miners under the age of 60 was better associated with the time weighted index of exposure to chromium than to the time weighted duration of exposure to dust in gold mines. Although the number of cases of gastric cancer that were classified according to the system of Lauren was small, the data suggest that for miners under the age of 60, exposure to chromium is associated with the development of the intestinal rather than the diffuse type of gastric cancer.

Use of provincial health insurance plan billing data to estimate carpal tunnel syndrome morbidity and surgery rates.

Following a work refusal at a plant manufacturing ice cream novelties in Ontario, we were asked to document cases of cumulative trauma disorders (CTDs) and carpal tunnel syndrome (CTS) in this workplace. There were 17 employees with possible hand and wrist problems identified from Workers Compensation Board (WCB) Forms, and from a list prepared at the time of the refusal. After obtaining consents, confirmations of the diagnoses of CTDs, CTS, and of surgical procedures for CTS were obtained from the physicians involved. The relative risk for these disorders among plant employees was estimated in two ways: 1) the rate of CTS operations between 1979 and 1990 was compared to that in the general population using Ontario Health Insurance Plan (OHIP) data on physicians' billings for these operations; and 2) the frequency of WCB first payment claims for tendinitis and CTS during 1987 to 1989 at the plant was compared to that among the entire labor force of Ontario. CTDs had been diagnosed in all 17 workers: 9 had had operations for CTS, but one had had this operation prior to working at the plant. Compared to the remaining 8 workers who had CTS operations, an estimated 0.08 CTS operations would be expected among the 150 employees on the plant's seniority lists between 1979 and 1990, if the estimated rates in the general population were present at the plant, giving a Standardized Morbidity Ratio of 10.0 (95% confidence interval [CI] 4.3-19.7; one-sided p = 2.1 x 10(-6)). There were 6 WCB claims for tendinitis and CTS among plant employees during 1987 through 1989. This frequency was about 68 times that in the entire Ontario labor force (95% CI 24.7-150). This investigation has shown that CTDs, and particularly CTS, documented by medical records, have occurred at least 10 times more frequently than expected at this plant. Use of health insurance billing data to estimate CTS operation rates represents a simple method for estimating the burden of illness at the individual plant level due to CTS (at least for that portion proceeding to surgery), using an objective outcome that can be confirmed from medical records.

Mortality among workers receiving compensation awards for silicosis in Ontario 1940-85.

The mortality experience of 1190 miners and 289 surface industry workers receiving workers' compensation awards for silicosis in Ontario since 1940 has been studied up to mid-1985. Both groups were found to have a significantly increased mortality from lung cancer (miners' SMR: 230; surface workers' SMR: 302) and stomach cancer (miners' SMR: 188; surface workers' SMR: 366). Adjustment for smoking and country of origin did not explain the excesses observed. The lung cancer findings are consistent with observations from silicosis registries in Europe. Possible explanatory factors are discussed.

Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.