Lung cancer risk associated to exposure to radon and smoking in a case-control study of French uranium miners

A case-control study nested in the cohort of French uranium miners took smoking information into account in investigating the effect of radon exposure on lung cancer risk. This study included 100 miners who died of lung cancer and 500 controls matched for birth period and attained age. Data about radon exposure came from the cohort study, and smoking information was retrospectively determined from a questionnaire and occupational medical records. Smoking status (never vs. ever) was reconstructed for 62 cases and 320 controls. Statistical analyses used conditional logistic regression. The effect of radon exposure on lung cancer risk was assessed with a linear excess relative risk model, and smoking was considered as a multiplicative factor. Mean cumulative radon exposures were 114.75 and 70.84 Working Level Months (WLM) among exposed cases and controls, respectively. The crude excess risk of lung cancer per 100 WLM was 0.98 (95% CI: 0.18-3.08%). When adjusted for smoking, the excess risk was 0.85 per 100 WLM (95% CI: 0.12-2.79%), which is still statistically significant. The relative risk related to smoking was equal to 3.04 (95% CI: 1.20-7.70). This analysis shows a relative risk of lung cancer related to smoking similar to that estimated from previous miners' cohorts. After adjustment for smoking, the effect of radon exposure on lung cancer risk persists, and its estimated risk coefficient is close to that found in the French cohort without smoking information.     

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.     

Lung cancer and indoor exposure to coal and biomass in rural China

Incomplete combustion of coal in homes has been linked with lung cancer in China. We report on a lung cancer case-control study in a rural area of China, where many residents live in underground dwellings and burn coal and unprocessed biomass (crop residues, wood, sticks, and twigs) for heating and cooking. We interviewed 846 patients with lung cancer (626 men, 220 women; aged 30 to 75 years) diagnosed between 1994 and 1998, and 1740 population-based controls. The odds ratio for lung cancer associated with coal use compared with that for biomass in the house of longest residence was 1.29 (95% confidence interval, 1.03 to 1.61), adjusted for smoking and socioeconomic status. The risk for lung cancer increased relative to the percentage of time that coal was used over the past 30 years (P = 0.02). Our findings suggest that coal may contribute to the risk of lung cancer in this rural area of China.     

Lung cancer and residency--a case-referent study on the possible impact of of exposure to radon and its daughters in dwellings.

In view of the well-known urban-rural difference in lung cancer rates, remaining also after standardization for smoking, it is suggested that low levels of radon and its daughters in dwellings might be of etiologic importance to this disease. To test this hypothesis, a case-referent (case-control) study was undertaken in a rural area; it considered residency in wooden houses (assumed to be associated with low-level exposure to radon and its daughters), "mixed type" houses (medium exposure) and stone houses (high-level exposure) among cases of lung cancer and referents (controls). The results indicate an increased risk of lung cancer among residents in "mixed type" and stone houses. Additional studies are highly desirable to confirm or refute these findings, which, if valid, mean increasing lung cancer hazards caused by a decrease in ventilation in future energy saving unless special measures are undertaken to reduce radon daughters in dwellings.     

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 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 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).     

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.     

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.     

Residential radon exposure and lung cancer risk: commentary on Cohen's county-based study

The large United States county-based study () in which an inverse relationship has been suggested between residential low-dose radon levels and lung cancer mortality has been reviewed. While this study has been used to evaluate the validity of the linear nonthreshold theory, the grouped nature of its data limits the usefulness of this application. Our assessment of the study's approach, including a reanalysis of its data, also indicates that the likelihood of strong, undetected confounding effects by cigarette smoking, coupled with approximations of data values and uncertainties in accuracy of data sources regarding levels of radon exposure and intensity of smoking, compromises the study's analytic power. The most clear data for estimating lung cancer risk from low levels of radon exposure continue to rest with higher-dose studies of miner populations in which projections to zero dose are consistent with estimates arising from most case-control studies regarding residential exposure.     

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.     

Malignant mesothelioma: attributable risk of asbestos exposure.

OBJECTIVES--To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS--Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS--Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS--Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.     

Design issues in epidemiologic studies of indoor exposure to Rn and risk of lung cancer

Recent data on indoor air quality have indicated that Rn (222Rn) and its decay products are frequently present in domestic environments. Since studies of Rn-exposed miners have established that Rn decay products are a lung carcinogen, their presence in indoor air raises concerns about an increase in lung cancer risk for the general population. To directly evaluate lung cancer risk from domestic exposure to Rn and its decay products, as well as to evaluate risk assessments derived from studies of Rn-exposed underground miners, several epidemiologic studies of indoor Rn exposure have been initiated or are planned. This paper calculates sample sizes required for a hypothetical case-control study to address several important hypotheses and shows the impact of several difficult problems associated with estimating a subject's Rn exposure. We consider the effects of subject mobility, choice of the exposure response trend which is used to characterize an alternative hypothesis, and errors in the estimation of exposure. Imprecise estimation of Rn exposure arises from errors in the measurement device, exposure to Rn decay products from sources outside the home, inability to measure exposures over time in current as well as previous residences, and the unknown relationship between measured concentration and lung dose of alpha energy from the decay of Rn and its progeny. These methodological problems can result in large discrepancies between computed and actual study power. Failure to anticipate these problems in the design of a study can result in inaccurate estimates of power. We conclude that case-control studies of indoor Rn and lung cancer may require substantial numbers of subjects in order to address the many questions of importance that burden current risk assessments with uncertainty. We suggest pooling data from studies with the largest numbers of cases and with the most precise estimates of Rn exposure as the best approach for meeting present research needs.     

Population attributable fraction for lung cancer due to residential radon in Switzerland and Germany

Studies on miners as well as epidemiological studies in the general population show an increased lung cancer risk after exposure to radon and its progeny. The European pooled analysis of indoor radon studies estimates an excess relative risk of 8% (16% after correction for measurement uncertainties) per 100 Bq m(-3) indoor radon concentration. Here, we determine the population attributable fraction (PAF) for lung cancer due to residential radon based on this risk estimate for Switzerland and Germany. Based on regionally stratified radon data, the PAF was calculated following the World Health Organization concept of global burden of disease, compared to a realistic baseline radon concentration equal to the outdoor concentration. Lifetable approaches were used taking smoking and sex into account. Measurement error corrections were applied to both risk estimates and the radon distribution. In Switzerland, the average indoor radon concentration is 78 Bq m(-3), resulting in a PAF of 8.3%. Therefore, 169 male lung cancer deaths and 62 deaths in women can be attributed to residential radon per year. For Germany, the average indoor radon concentration is 49 Bq m(-3), corresponding to a PAF of 5.0% (1,422 male and 474 female deaths annually). In both countries, a large regional variation in the PAF was observed due to regional differences in radon concentrations and population structure. Both calculations show a strong dependency on the risk model used. Risk models based on miner studies result in higher PAF estimates than risk models based on indoor radon studies due to different assumptions regarding exposures received more than 35 years ago. The use of a non-zero baseline radon concentration also contributes to the lower PAF estimates reported here. Although the estimates of the population attributable fraction of residential radon presented here are lower than previously reported estimates, the risk is still one of the most widespread environmental hazards. Radon monitoring and radon reduction programs are therefore important issues for environmental public health management.     

210Po implanted in glass surfaces by long term exposure to indoor radon

Recent epidemiologic investigations of the relationship between residential radon gas exposure and lung cancer relied on contemporary radon gas measurements to estimate past radon gas exposures. Significant uncertainties in these exposure estimates can arise from year-to-year variation of indoor radon concentrations and subject mobility. Surface implanted 210Po has shown potential for improving retrospective radon gas exposure estimates. However, in previous studies, the ability of implanted 210Po activity to reconstruct cumulative radon gas exposure was not tested because glass was not available from homes with known radon-gas concentration histories. In this study, we tested the validity of the retrospective radon gas reconstruction using implanted 210Po surface activity by measuring glass surfaces from homes whose annual-average radon gas concentrations had been measured almost every year during two decades. Regression analysis showed a higher correlation between measured surface activity and cumulative radon gas exposure in these homes (R2>0.8) than was observed in homes where only contemporary radon gas measurements were available. The regression slope (0.57 ky m(-1)) was consistent with our earlier retrospective results. Surface activity measurements were as reliable for retrospective radon gas exposure reconstruction as yearlong gas measurements. Both methods produced estimates that were within 25% of the long-term average radon gas concentrations in a home. Surface measurements can be used for home screening tests because they can provide rapid, reliable estimates of past radon gas concentrations. Implanted 210Po measurements are also useful in retrospective epidemiologic studies that include participants who may have been exposed to highly variable radon concentrations in previously occupied or structurally modified homes.     

Models for retrospective quantification of indoor radon exposure in case-control studies

In epidemiologic studies on lung cancer risk due to indoor radon the quantification of individual radon exposure over a long time period is one of the main issues. Therefore, radon measurements in one or more dwellings, which in total have been inhabited by the participants for a sufficient time-period, are necessary as well as consideration of changes of building characteristics and ventilation habits, which influence radon concentration. Given data on 1-y alpha-track measurements and personal information from 6,000 participants of case-control studies in West and East Germany, an improved method is developed to assess individual radon exposure histories. Times spent in different rooms of the dwelling, which are known from a personal questionnaire, are taken into account. The time spent outside the house (average fraction 45%) varies substantially among the participants. Therefore, assuming a substantially lower radon exposure outside the dwelling, the residence time constitutes an important aspect of total radon exposure. By means of an analysis of variance, important determinants of indoor radon are identified, namely constant conditions such as type of house (one family house or multiple dwelling), type of construction (half-timbered, massive construction, lightweight construction), year of construction, floor and type of basement, and changeable conditions such as heating system, window insulation, and airing habits. A correction of measurements in former dwellings by factors derived from the analysis is applied if current living conditions differ from those of the participants at the time when they were living in the particular dwellings. In rare cases the adjustment for changes leads to a correction of the measurements with a factor of about 1.4, but a reduction of 5% on average only. Exposure assessment can be improved by considering time at home and changes of building and ventilation conditions that affect radon concentration. The major concern that changes in ventilation habits and building conditions lead to substantial errors in exposure (and therefore risk) assessment cannot be confirmed in the data analyzed.