Residential radon exposure and lung cancer: risk in nonsmokers

Lung cancer is a disease that is almost entirely caused by smoking; hence, it is almost totally preventable. Yet there are a small percentage of cases, perhaps as many as 5 to 15%, where there are other causes. Risk factors identified for this other group include passive smoking, occupational exposure to certain chemicals and ionizing radiation, diet, and family history of cancer. In the United States cigarette smoking is on the decline among adults, occupational exposures are being reduced, and people are being made more aware of appropriate diets. These changes are gradually resulting in a reduced risk for this disease. Lung cancer in the U.S. may, therefore, eventually become largely a disease of the past. It remains important, however, to continue to study the cause(s) of lung cancer in non-smokers, particularly never smokers. Because of our interest in the effects of residential radon exposure on the development of lung cancer in non-smokers, we conducted a critical review of the scientific literature to evaluate this issue in detail. Strict criteria were utilized in selecting studies, which included being published in a peer reviewed journal, including non-smokers in the studied populations, having at least 100 cases, and being of case-control design. A total of 12 individual studies were found that met the criteria, with 10 providing some information on non-smokers. Most of these studies did not find any significant association between radon and lung cancer in non-smokers. Furthermore, data were not presented in sufficient detail for non-smokers in a number of studies. Based on the most recent findings, there is some evidence that radon may contribute to lung cancer risk in current smokers in high residential radon environments. The situation regarding the risk of lung cancer from radon in non-smokers (ex and never) is unclear, possibly because of both the relatively limited sample size of non-smokers and methodological limitations in most of the individual studies. A summary of these studies is provided concerning the state of knowledge of the lung cancer risk from radon, methodological problems with the residential studies, the need for the provision of additional data on non-smokers from researchers, and recommendations for future research in non-smokers.     

Residential radon exposure and risk of lung cancer in Missouri.

OBJECTIVES: This study investigated residential radon exposure and lung cancer risk, using both standard radon dosimetry and a new radon monitoring technology that, evidence suggests, is a better measure of cumulative radon exposure. METHODS: Missouri women (aged 30 to 84 years) newly diagnosed with primary lung cancer during the period January 1, 1993, to January 31, 1994, were invited to participate in this population-based case-control study. Both indoor air radon detectors and CR-39 alpha-particle detectors (surface monitors) were used. RESULTS: When surface monitors were used, a significant trend in lung cancer odds ratios was observed for 20-year time-weighted-average radon concentrations. CONCLUSIONS: When surface monitors were used, but not when standard radon dosimetry was used, a significant lung cancer risk was found for radon concentrations at and above the action level for mitigation of houses currently used in the United States (148 Bqm-3). The risk was below the action level used in Canada (750 Bqm-3) and many European countries (200-400 Bqm-3).     

Residential radon exposure and lung cancer: variation in risk estimates using alternative exposure scenarios

The most direct way to derive risk estimates for residential radon progeny exposure is through epidemiologic studies that examine the association between residential radon exposure and lung cancer. However, the National Research Council concluded that the inconsistency among prior residential radon case-control studies was largely a consequence of errors in radon dosimetry. This paper examines the impact of applying various epidemiologic dosimetry models for radon exposure assessment using a common data set from the Iowa Radon Lung Cancer Study (IRLCS). The IRLCS uniquely combined enhanced dosimetric techniques, individual mobility assessment, and expert histologic review to examine the relationship between cumulative radon exposure, smoking, and lung cancer. The a priori defined IRLCS radon-exposure model produced higher odds ratios than those methodologies that did not link the subject's retrospective mobility with multiple, spatially diverse radon concentrations. In addition, the smallest measurement errors were noted for the IRLCS exposure model. Risk estimates based solely on basement radon measurements generally exhibited the lowest risk estimates and the greatest measurement error. The findings indicate that the power of an epidemiologic study to detect an excess risk from residential radon exposure is enhanced by linking spatially disparate radon concentrations with the subject's retrospective mobility.     

Residential radon exposure and lung cancer in Swedish women.

A case-control study was undertaken to investigate the role of residential radon exposure for lung cancer. The study included 210 women with lung cancer diagnosed from 1983-1986 in the county of Stockholm and 191 hospital and 209 population controls. Interviews provided information on lifetime residences and smoking. Radon concentrations measured in 1,573 residences of the study subjects showed a lognormal distribution with arithmetic and geometric means of 127.7 and 96.0 Bq m-3, respectively. Lung cancer risks tended to increase with estimated radon exposure, reaching a relative risk of 1.7 (95% confidence interval: 1.0-2.9) in women having an average radon level exceeding 150 Bq m-3 (4 pCi L-1). Stronger associations were suggested in younger persons and risk estimates appeared to be within the same range as those projected for miners. However, further studies are needed to clarify the level of risk associated with exposure to residential radon.     

Residential radon and risk of lung cancer in Eastern Germany

BACKGROUND: There is suggestive evidence that residential radon increases lung cancer risk. To elucidate this association further, we conducted a case-control study in Thuringia and Saxony in Eastern Germany during 1990-1997. METHODS: Histologically confirmed lung cancer patients from hospitals and a random sample of population controls matched on age, sex and geographical area were personally interviewed with respect to residential history, smoking, and other risk factors. One-year radon measurements were performed in houses occupied during the 5-35 years prior to the interview. The final analysis included a total of 1,192 cases and 1,640 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. RESULTS: Measurements covered on average 72% of the exposure time window, with mean radon concentrations of 76 Bq/m3 among the cases and 74 Bq/m3 among the controls. The smoking- and asbestos-adjusted ORs for categories of radon (50-80, 80-140 and >140 Bq/m*3, compared with 0-50 Bq/m3) were 0.95 (CI = 0.77 to 1.18), 1.13 (CI = 0.86 to1.50) and 1.30 (CI = 0.88 to 1.93). The excess relative risk per 100 Bq/m? was 0.08 (CI = -0.03 to 0.20) for all subjects and 0.09 (CI = -0.06 to 0.27) for subjects with complete measurements for all 30 years. CONCLUSIONS: Our data indicate a small increase in lung cancer risk as a result of residential radon that is consistent with the findings of previous indoor radon and miner studies.     

Residential radon exposure and lung cancer: an overview of ongoing studies.

This review paper summarizes the ongoing case/control studies of residential radon exposure and lung cancer. Discussion is offered in the areas of lung cancer risk factors, sample size requirements, radon exposure assessment, and meta-analysis. This is an important topic that deserves a "best effort" study design.     

Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study

Exposure to high concentrations of radon progeny (radon) produces lung cancer in both underground miners and experimentally exposed laboratory animals. To determine the risk posed by residential radon exposure, the authors performed a population-based, case-control epidemiologic study in Iowa from 1993 to 1997. Subjects were female Iowa residents who had occupied their current home for at least 20 years. A total of 413 lung cancer cases and 614 age-frequency-matched controls were included in the final analysis. Excess odds were calculated per 11 working-level months for exposures that occurred 5-19 years (WLM(5-19)) prior to diagnosis for cases or prior to time of interview for controls. Eleven WLM(5-19) is approximately equal to an average residential radon exposure of 4 pCl/liter (148 Bq/m3) during this period. After adjustment for age, smoking, and education, the authors found excess odds of 0.50 (95% confidence interval: 0.004, 1.81) and 0.83 (95% percent confidence interval: 0.11, 3.34) using categorical radon exposure estimates for all cases and for live cases, respectively. Slightly lower excess odds of 0.24 (95 percent confidence interval: -0.05, 0.92) and 0.49 (95 percent confidence interval: 0.03, 1.84) per 11 WLM(5-19) were noted for continuous radon exposure estimates for all subjects and live subjects only. The observed risk estimates suggest that cumulative ambient radon exposure presents an important environmental health hazard.     

Residential radon and risk of lung cancer in an Italian alpine area

To evaluate whether residential radon exposure explains the excess mortality for lung cancer in an Italian alpine valley with high natural radioactivity, the authors conducted a population-based case-control study on 138 deceased cases and 291 sex- and year-of-birth-matched controls. Year-long alpha-track measurements of radon were performed in the most recent residence, and information about occupational history and lifetime smoking habits was obtained. The authors adjusted for smoking, and radon was associated with lung cancer risk among men: compared with a radon level of < 40 becquerels (Bq) per cubic meter (m3), the odds ratios for 40-76 Bq/m3, 77-139 Bq/m3, 140-199 Bq/m3, and 200+ Bq/m3 were 2.1, 2.0, 2.7, and 1.4, respectively. The association between radon and lung cancer, as determined with a multiplicative model, was found only among male smokers.     

Indoor radon exposure and lung cancer risk: a review of case-control studies

BACKGROUND: Radon is a radioactive gas that tends to accumulate in indoor environment. A causal relationship between lung cancer and radon exposure has been demonstrated in epidemiologic studies of miners. The objective of this paper is to present the results of case-control studies of lung cancer risk associated with indoor radon exposure. METHODS: Case-control studies published since 1990 are included in this review. This type of protocol is particularly well suited for studying the relationship between indoor radon exposure and lung cancer risk, taking into account possible confounding factors such as tobacco smoking. The characteristics and results of these studies are summarized. The limitations associated with each of these studies are also discussed. RESULTS: The results of available studies are relatively concordant and suggest a positive association between lung cancer risk and indoor radon exposure with an estimated excess relative risk of about 6 to 9% per 100Bq/m3 increase in the observed time-weighted average radon concentration. The order of magnitude of this estimation agrees with extrapolations from miners but some studies may suffer from inadequate statistical power. CONCLUSION: At present, efforts are underway to pool together the data from the existing studies of indoor radon. This pooling analysis with thousands of cases and controls will provide a more precise estimate of the lung cancer risk from indoor radon exposure and explore the effect of modifying factors, such as smoking.     

Residential randon exposure and lung cancer risk in Misasa, Japan: a case-control study

In order to investigate an association between residential radon exposure and risk of lung cancer, a case-control study was conducted in Misasa Town, Tottori Prefecture, Japan. The case series consisted of 28 people who had died of lung cancer in the years 1976-96 and 36 controls chosen randomly from the residents in 1976, matched by sex and year of birth. Individual residential radon concentrations were measured for 1 year with alpha track detectors. The average radon concentration was 46 Bq/m3 for cases and 51 Bq/m3 for controls. Compared to the level of 24 or less Bq/m3, the adjusted odds ratios of lung cancer associated with radon levels of 25-49, 50-99 and 100 or more Bq/m3, were 1.13 (95% confidence interval; 0.29-4.40), 1.23 (0.16-9.39) and 0.25 (0.03-2.33), respectively. None of the estimates showed statistical significance, due to small sample size. When the subjects were limited to only include residents of more than 30 years, the estimates did not change substantially. This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.     

Case-control study of lung cancer risk from residential radon exposure in Worcester county, Massachusetts

A study of lung cancer risk from residential radon exposure and its radioactive progeny was performed with 200 cases (58% male, 42% female) and 397 controls matched on age and sex, all from the same health maintenance organization. Emphasis was placed on accurate and extensive year-long dosimetry with etch-track detectors in conjunction with careful questioning about historic patterns of in-home mobility. Conditional logistic regression was used to model the outcome of cancer on radon exposure, while controlling for years of residency, smoking, education, income, and years of job exposure to known or potential carcinogens. Smoking was accounted for by nine categories: never smokers, four categories of current smokers, and four categories of former smokers. Radon exposure was divided into six categories (model 1) with break points at 25, 50, 75, 150, and 250 Bq m, the lowest being the reference. Surprisingly, the adjusted odds ratios (AORs) were, in order, 1.00, 0.53, 0.31, 0.47, 0.22, and 2.50 with the third category significantly below 1.0 (p < 0.05), and the second, fourth, and fifth categories approaching statistical significance (p < 0.1). An alternate analysis (model 2) using natural cubic splines allowed calculating AORs as a continuous function of radon exposure. That analysis produces AORs that are substantially less than 1.0 with borderline statistical significance (0.048 < or = p < or = 0.05) between approximately 85 and 123 Bq m. College-educated subjects in comparison to high-school dropouts have a significant reduction in cancer risk after controlling for smoking, years of residency, and job exposures with AOR = 0.30 (95% CI: 0.13, 0.69), p = 0.005 (model 1).     

Predicted reduction in lung cancer risk following cessation of smoking and radon exposure

Recently there has been considerable public and regulatory concern that radon, produced by the decay of naturally occurring uranium, can accumulate in homes, offices, and schools at levels that may substantially increase the risk of lung cancer. The major cause of lung cancer is smoking, and radon appears to interact multiplicatively with smoking in causing lung cancer. Thus, the most effective way to reduce the increased risk of lung cancer resulting from radon exposure is to cease smoking. In this paper, a model for the risks associated with radon exposure that was developed by a committee of the National Academy of Sciences is used to calculate the benefits, in terms of reduction in lifetime risk of lung cancer, of ceasing to smoke, ceasing radon exposure, or ceasing both. Ceasing to smoke is considerably more beneficial than ceasing radon exposure, and thus policymakers addressing the health effects of radon should place priority on encouraging individuals to stop smoking.     

Residential radon and lung cancer risk in a high-exposure area of Gansu Province, China

In the general population, evaluation of lung cancer risk from radon in houses is hampered by low levels of exposure and by dosimetric uncertainties due to residential mobility. To address these limitations, the authors conducted a case-control study in a predominantly rural area of China with low mobility and high radon levels. Included were all lung cancer cases diagnosed between January 1994 and April 1998, aged 30-75 years, and residing in two prefectures. Randomly selected, population-based controls were matched on age, sex, and prefecture. Radon detectors were placed in all houses occupied for 2 or more years during the 5-30 years prior to enrollment. Measurements covered 77% of the possible exposure time. Mean radon concentrations were 230.4 Bq/m(3) for cases (n = 768) and 222.2 Bq/m(3) for controls (n = 1,659). Lung cancer risk increased with increasing radon level (p < 0.001). When a linear model was used, the excess odds ratios at 100 Bq/m(3) were 0.19 (95% confidence interval: 0.05, 0.47) for all subjects and 0.31 (95% confidence interval: 0.10, 0.81) for subjects for whom coverage of the exposure interval was 100%. Adjusting for exposure uncertainties increased estimates by 50%. Results support increased lung cancer risks with indoor radon exposures that may equal or exceed extrapolations based on miner data.     

Residential radon and risk of lung cancer: a combined analysis of 7 North American case-control studies

BACKGROUND: Underground miners exposed to high levels of radon have an excess risk of lung cancer. Residential exposure to radon is at much lower levels, and the risk of lung cancer with residential exposure is less clear. We conducted a systematic analysis of pooled data from all North American residential radon studies. METHODS: The pooling project included original data from 7 North American case-control studies, all of which used long-term alpha-track detectors to assess residential radon concentrations. A total of 3662 cases and 4966 controls were retained for the analysis. We used conditional likelihood regression to estimate the excess risk of lung cancer. RESULTS: Odds ratios (ORs) for lung cancer increased with residential radon concentration. The estimated OR after exposure to radon at a concentration of 100 Bq/m3 in the exposure time window 5 to 30 years before the index date was 1.11 (95% confidence interval = 1.00-1.28). This estimate is compatible with the estimate of 1.12 (1.02-1.25) predicted by downward extrapolation of the miner data. There was no evidence of heterogeneity of radon effects across studies. There was no apparent heterogeneity in the association by sex, educational level, type of respondent (proxy or self), or cigarette smoking, although there was some evidence of a decreasing radon-associated lung cancer risk with age. Analyses restricted to subsets of the data with presumed more accurate radon dosimetry resulted in increased estimates of risk. CONCLUSIONS: These results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted using miner data and consistent with results from animal and in vitro studies.     

A case-control study of lung cancer relative to domestic radon exposure

Public concern was expressed regarding the possibility of adverse health effects with the disposal of radioactive waste in Port Hope, Ontario. A case-control study was carried out to estimate the relative importance of domestic radon gas exposure in the causation of lung cancer in the town over a ten-year period. Twenty-seven cases met the entry criteria. Statistical analyses of results did not provide conclusive results that linked an increased risk of lung cancer and elevated domestic alpha radiation levels, when all factors were considered. However, a very strong association was demonstrated between cigarette smoking and lung cancer.     

Residential radon and lung cancer among never-smokers in Sweden.

In this study, we attempted to reduce existing uncertainty about the relative risk of lung cancer from residential radon exposure among never-smokers. Comprehensive measurements of domestic radon were performed for 258 never-smoking lung cancer cases and 487 never-smoking controls from five Swedish case-control studies. With additional never-smokers from a previous case-control study of lung cancer and residential radon exposure in Sweden, a total of 436 never-smoking lung cancer cases diagnosed in Sweden between 1980 and 1995 and 1,649 never-smoking controls were included. The relative risks (with 95% confidence intervals in parentheses) of lung cancer in relation to categories of time-weighted average domestic radon concentration during three decades, delimited by cutpoints at 50, 80, and 140 Bq m(-3), were 1.08 (0.8--1.5), 1.18 (0.9--1.6), and 1.44 (1.0--2.1), respectively, with average radon concentrations below 50 Bq m(-3) used as reference category and with adjustment for other risk factors. The data suggested that among never-smokers residential radon exposure may be more harmful for those exposed to environmental tobacco smoke. Overall, an excess relative risk of 10% per 100 Bq m(-3) average radon concentration was estimated, which is similar to the summary effect estimate for all subjects in the main residential radon studies to date.     

The potential for bias in Cohen's ecological analysis of lung cancer and residential radon.

Cohen's ecological analysis of US lung cancer mortality rates and mean county radon concentration shows decreasing mortality rates with increasing radon concentration (Cohen 1995 Health Phys. 68 157-74). The results prompted his rejection of the linear-no-threshold (LNT) model for radon and lung cancer. Although several authors have demonstrated that risk patterns in ecological analyses provide no inferential value for assessment of risk to individuals, Cohen advances two arguments in a recent response to Darby and Doll (2000 J. Radiol. Prot. 20 221-2) who suggest Cohen's results are and will always be burdened by the ecological fallacy. Cohen asserts that the ecological fallacy does not apply when testing the LNT model, for which average exposure determines average risk, and that the influence of confounding factors is obviated by the use of large numbers of stratification variables. These assertions are erroneous. Average dose determines average risk only for models which are linear in all covariates, in which case ecological analyses are valid. However, lung cancer risk and radon exposure, while linear in the relative risk, are not linearly related to the scale of absolute risk, and thus Cohen's rejection of the LNT model is based on a false premise of linearity. In addition, it is demonstrated that the deleterious association for radon and lung cancer observed in residential and miner studies is consistent with negative trends from ecological studies, of the type described by Cohen.     

Lifetime risk of lung cancer due to radon exposure projected to Japanese and Swedish populations

Lifetime risk projections depend greatly on both background lung cancer rates and the selection of the risk model. Since background lung cancer rates differ from subject populations and the time, etiological risk of lifetime lung cancer mortality per unit radon exposure in WLM should be estimated for each subject population and the time of interest. To answer quantitatively how much are the differences among the projected risks for different populations, the Swedish case-control-study-based risk projection model was applied to the Japanese and Swedish populations from 1962 to 1997 as subject populations because of their distinct trends of lung cancer rates. To compare the results with the reference population and authorized risk projection models, U.S. population 1997 and the two risk projection models in BEIR VI report were applied, respectively. Lifetime risk of lung cancer mortality projected for Japanese, Swedish, and U.S. populations in 1997 per radon progeny exposure were estimated to range from 1.50 (0.40-3.19) x 10(-4) WLM(-1) to 9.86 (2.62-20.9) x 10(-4) WLM(-1), which could be compared to the detriment associated with a unit effective dose. Conclusive dose conversion coefficients in this study ranged from 2.05 (0.55-4.37) to 13.5 (3.59-28.6) mSv WLM(-1), and within this range the discrepancy between dosimetric and epidemiological approaches was included.