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).     

The precautionary principle applied to lung cancer risk caused by residential radon

Residential radon seems to represent a major health hazard. The studies, which investigate the pulmonary risk of cancer caused by radon, are of different nature and their results are divergent. Thus, there persist scientific uncertainties concerning the real size of this risk. The application of the precautionary principle is based on an analysis of these uncertainties. Studies on miners, studies concerning residential radon (at individual and ecological level), as well as experimental data allow for the organisation of the uncertainty of each one of these specific approaches taking into account their proper limitations. The first risk that is linked to radon is the risk of pulmonary cancer. Miner occupational exposure studies appear compatible with the results of case-control studies concerning residential radon. However, the case-control studies, where the risk appears more present, are contradicted by ecological studies, often not very convincing about the existence of a risk. The case-control studies have an intrinsic advantage over the ecological studies because they limit the classification errors by the individualization of the relation-exposure effect. In addition, the experimental data are not in contradiction with the existence of effects for very small exposures. Consequently, the inherent scientific uncertainties of the totality of these data, can be classified and permit the application of the precautionary principle in a better proportioned way. The utilisation of the precautionary principle implies the necessity to limit, as far as possible, the exposure to residential radon. Precautionary principle is based on the debated hypothesis of no threshold linear relation between radon exposition and health consequences. This relation has been established on professional and residential exposures. The implementation of this epidemiological model shows the "residential radon" risk as the second cause of pulmonary cancer and responsible of about 10% of these specific cancers.     

Effects of residential mobility on individual versus population risk of radon-related lung cancer.

The U.S. Environment Protection Agency (EPA) does not consider the effects of normal patterns of residential mobility in estimating individual radon-related lung cancer risks. As a consequence, the EPA's population risk estimates may have little bearing on individual risks, and remediation of high-radon homes may have only small health benefits for the individual who remediate their homes. Through a stimulation analysis, we examine the effects of residential mobility on random exposure and lung cancer risk. Given normal mobility, only 7% of eventual radon-related mortality among current 30 year old will occur in the 5% currently living in homes above pCi/l (the EPA's action level for remediation) in contrast with you estimate of 31% of deaths when mobility's ignored. About 10 pCi/l the no-mobility assumption implies 10.3% of deaths, compared to only 0.4% when mobility taken into account. We conclude that knowledge of one's current random exposure not necessarily a useful guide to one's risk, especially for residents of the high-radon homes targeted for remediation by the EPA. The risk of such individuals is like to be substantially lower than that implied in the EPA's risk charts. If people currently living in high radon homes remediate their houses, the majority of the resulting health benefits will accrue to future occupants of their homes.     

Study of lung cancer and residential radon in the Czech Republic

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines where exposures are relatively high in comparison to indoor exposure. Risk from residential radon can be estimated from occupational studies. Nevertheless, as such extrapolations depend on a number of assumptions, direct estimation of the risk is needed. The present study of lung cancer mortality was designed as a follow-up of a population (N = 12,004) in a radon prone area of the Czech Republic covering the period 1960-1999. Information on vital status and causes of death were obtained mostly from local authorities and from the national population registry. Exposure estimates were based on one year measurements of radon progeny in most houses of the study area (74%). Exposures outside the area (16%) were based on country radon mapping. Mean concentration of 509 Bq/m3 is higher than the country estimate by a factor of 5. By 1999, a total of 210 lung cancers were observed, somewhat more than the nationally expected number (O/E = 1.10) in comparison to generally low numbers corresponding to cancers other than lung (O/E = 0.81). The excess relative risk per standard radon concentration (100 Bq/m3) was 0.087 (90% CI: 0.017-0.208). This value is consistent with risk coefficients derived in other indoor studies. The present follow-up demonstrated that increased incidence of lung cancer depends linearly on exposure in terms of average radon concentration in the course of previous 5-34 years. Adjustment for smoking did not substantially change this estimate, although the risk coefficient for non-smokers (0.130) was higher in comparison to that for ever smokers (0.069), but not statistically different.     

Meta-analysis of residential exposure to radon gas and lung cancer

OBJECTIVES: To investigate the relation between residential exposure to radon and lung cancer. METHODS: A literature search was performed using Medline and other sources. The quality of studies was assessed. Adjusted odds ratios with 95% confidence intervals (CI) for the risk of lung cancer among categories of levels of exposure to radon were extracted. For each study, a weighted log-linear regression analysis of the adjusted odds ratios was performed according to radon concentration. The random effect model was used to combine values from single studies. Separate meta-analyses were performed on results from studies grouped with similar characteristics or with quality scores above or equal to the median. FINDINGS: Seventeen case-control studies were included in the meta-analysis. Quality scoring for individual studies ranged from 0.45 to 0.77 (median, 0.64). Meta-analysis based on exposure at 150 Bq/m3 gave a pooled odds ratio estimate of 1.24 (95% CI, 1.11-1.38), which indicated a potential effect of residential exposure to radon on the risk of lung cancer. Pooled estimates of fitted odds ratios at several levels of randon exposure were all significantly different from unity--ranging from 1.07 at 50 Bq/m3 to 1.43 at 250 Bq/m3. No remarkable differences from the baseline analysis were found for odds ratios from sensitivity analyses of studies in which > 75% of eligible cases were recruited (1.12, 1.00-1.25) and studies that included only women (1.29, 1.04-1.60). CONCLUSION: Although no definitive conclusions may be drawn, our results suggest a dose-response relation between residential exposure to radon and the risk of lung cancer. They support the need to develop strategies to reduce human exposure to radon.     

Exposure to residential radon and lung cancer in Spain: a population-based case-control study

Although high radon concentrations have been linked to increased risk of lung cancer by both experimental studies and investigations of underground miners, epidemiologic studies of residential radon exposure display inconsistencies. The authors therefore decided to conduct a population-based case-control study in northwest Spain to determine the risk of lung cancer associated with exposure to residential radon. The study covered a total of 163 subjects with incident lung cancer and a population sample of 241 cancer-free subjects since 1992-1994. Odds ratios for radon were estimated using logistic regression adjusted for sex, age, lifetime tobacco use, family history, and habitat. The adjusted odds ratios for the second, third, and fourth quartiles of radon (breakpoints: 37.0, 55.2, and 148.0 Bq/m(3)) were 2.73 (95% confidence interval (CI): 1.12, 5.48), 2.48 (95% CI: 1.29, 6.79), and 2.96 (95% CI: 1.29, 6.79), respectively. An additive synergic effect between radon and tobacco was found. The results from this study suggest that, even at concentrations far below official guideline levels, radon may lead to a 2.5-fold rise in the risk of lung cancer. Furthermore, the synergy found between smoking and radon may prove useful when it comes to drafting public health recommendations.     

Increased lung cancer risk due to residential radon in a pooled and extended analysis of studies in Germany

Residential radon has been shown to be a risk factor for lung cancer in several studies-but with limited power in each single study. The data of two case-control studies performed during 1990-1997 in Germany and used for previous publications have been extended and pooled. Both studies have identical study designs. In total, data of 2,963 incident lung cancer cases and 4,232 population controls are analyzed here. One-year radon measurements were performed in houses occupied during the 5-35 y prior to the interview. Conditional logistic and linear relative risk regression was used for the analysis. Measurements covered on average 70% of the exposure time window, with an average radon exposure of 61 Bq m(-3). The smoking and asbestos-adjusted ORs were 0.97 [95% confidence interval (CI) 0.85 to 1.11] for 50-80 Bq m(-3), 1.06 (95% CI 0.87 to 1.30) for 80-140 Bq m(-3) and 1.40 (95% CI 1.03 to 1.89) for radon concentrations above 140 Bq m(-3), compared to the reference category <50 Bq m(-3). The linear increase in the odds ratio per 100 Bq m(-3) was 0.10 (95% CI -0.02 to 0.30) for all subjects and 0.14 (95% CI -0.03 to 0.55) for less mobile subjects who lived in only one home in the last 5-35 y. The risk coefficients generally were higher when measurement error in the radon concentrations was reduced by restricting the population. With respect to histopathology, the risk for small cell carcinoma was higher than for other subtypes. This analysis strengthens the evidence that residential radon is a relevant risk factor for lung cancer.     

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.     

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.     

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.     

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.     

阳江高本底地区肺癌与室内氡暴露巢式病例-对照研究

目的研究居室氡暴露与肺癌危险的关系。方法采用巢式病例-对照研究设计,病例与对照为1∶2个体配比。以面访的方式访问调查对象的家属或其他知情人。用固体核径迹探测器方法,对调查对象曾住房屋的氡浓度进行累积测量。结果成功访问了63例肺癌病例和125例对照,病例与对照的平均死亡年龄分别为60.1岁和60.6岁。病例和对照所在室内氡的平均浓度分别为40.1和39.2 Bq/m3。单因素条件logistic回归分析氡暴露与肺癌危险的关系,比值比[(OR)95%可信限(95%CI)]为1.25(0.63~2.52)。不同程度氡暴露,肺癌危险有增加趋势,但差异无统计学意义(P>0.05)。在100 Bq/m3氡浓度时,氡暴露的超额比值比(EOR)为0.30(95%CI:-0.53~14.93),调整钍射气贡献后,EOR=0.14。结论未发现室内氡暴露与肺癌危险有统计学意义的关联。     

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.     

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.     

Effects of radon mitigation vs smoking cessation in reducing radon-related risk of lung cancer.

OBJECTIVES: The purpose of this paper is to provide smokers with information on the relative benefits of mitigating radon and quitting smoking in reducing radon-related lung cancer risk. METHODS: The standard radon risk model, linked with models characterizing residential radon exposure and patterns of moving to new homes, was used to estimate the risk reduction produced by remediating high-radon homes, quitting smoking, or both. RESULTS: Quitting smoking reduces lung cancer risk from radon more than does reduction of radon exposure itself. CONCLUSIONS: Smokers should understand that, in addition to producing other health benefits, quitting smoking dominates strategies to deal with the problem posed by radon.     

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.     

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 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.