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).     

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.     

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.     

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.     

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.     

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.     

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.     

A case-referent study of lung cancer and incense smoke, smoking, and residential radon in Chinese men

Background: Burning incense generates large amounts of air pollutants, many of which are confirmed or suspected human lung carcinogens.Objectives: We conducted a population-based case-referent study to examine the effect of incense smoke exposure on lung cancer risk among Chinese males and explored the joint effect of cigarette smoking and exposure to residential radon.Methods: We recruited 1,208 male lung cancer incident cases and 1,069 community referents from 2004 to 2006 and estimated their lifetime exposures to incense smoke and other residential indoor air pollutants based on self-reported information collected during interviews. We performed unconditional multivariable logistic regression analysis to estimate the odds ratio (OR) for lung cancer associated with exposure to incense smoke after adjusting for possible confounders. We conducted stratified analyses by smoking status and exposures to incense burning and residential radon and explored the potential additive-scale interactions.Results: We observed an association between incense exposure and lung cancer that was limited primarily to smokers. Cigarette smoking and high cumulative incense exposure at home appeared to have a synergistic effect on lung cancer (compared with never-smokers who never used incense, the OR for lung cancer for smokers who used incense ≥ 60 day-years = 5.00; 95% confidence interval: 3.34, 7.51). Power was limited, but we also found preliminary evidence suggesting that radon exposure may increase risk among smokers using incense.Conclusion: Our study suggests that exposure to incense smoke in the home may increase the risk of lung cancer among smokers and that exposure to radon may further increase risk.     

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.     

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.     

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。     

Case-control study of lung cancer in Los Angeles county welders

A case-control study of lung cancer in white male welders was undertaken to investigate possible environmental and occupational causes of a 50% excess of lung cancer observed in this occupational group. The subjects were identified from a population-based cancer registry in Los Angeles County. A standardized questionnaire was administered to either subjects or proxy informants of 90 lung cancer cases and 116 non-lung-cancer controls. Significantly increased risks of lung cancer were associated with tobacco smoking (odds ratio 7.6, p less than .005) and shipyard welding with at least a 10-year latency since first exposure (odds ratio 1.7, p less than .05). Although there were elevated risks associated with some specific welding processes, none were statistically significant. Control subjects were more likely to have had exposure to confined-space welding (odds ratio 0.6, 95% CI = 0.3-1.2), and this association was greatest where there had been at least a 20-year latency since first exposure (0.5, 95% CI = 0.3-1.0). We conclude that the excess of lung cancer in this welding population is contributed to by a higher frequency of smoking and probable exposure to asbestos in shipyards. Other factors may be important, but probably because of limited power and reliance on proxy information, this study failed to detect other statistically significant risks.     

南京市肺癌环境危险因素的病例对照研究

目的探讨近年来南京市肺癌发生的环境危险因素.方法对南京市63例原发性肺鳞癌和89例原发性肺腺癌进行1:1配对病例-对照研究,并用条件Logistic回归模型分析危险因素.结果慢性支气管炎史、吸烟指数是肺鳞癌发生的环境危险因素,其OR值分别为8.55,2.35;人群归因危险度分别为18.22%,58.80%;综合人群归因危险度为0.6871.慢性支气管炎史、肺结核史、不良烹调习惯、煤炉使用年限、家族肿瘤史是肺腺癌发生的环境危险因素,OR值分别为5.16,4.12,2.91,2.02,2.59;人群归因危险度分别为8.15%,11.91%,27.30%,29.98%,10.35%;综合人群归因危险度为0.630 6.结论肺鳞癌、腺癌的发病分别与多种环境因素有关,应积极控制环境危险因素,以减少肺癌的发生率.     

Case-control study of physical activity and breast cancer risk among premenopausal women in Germany

Important aspects of the recognized inverse relation between physical activity and breast cancer risk are still under discussion. Data on physical activity from sports, occupational activity, household tasks, walking, and cycling by reported frequency, duration, and intensity during adolescence and young adulthood were collected in 1999-2000 from 360 premenopausal breast cancer cases and 886 controls who had previously participated in a German population-based case-control study. In multivariate conditional logistic regression, no association between total physical activity and premenopausal breast cancer was found in two age periods. For women who were active during both periods, the adjusted odds ratio was 0.83 (95% confidence interval: 0.60, 1.14). When both age periods were combined, higher quartiles of total physical activity compared with the lowest quartile showed adjusted odds ratios of 0.97, 0.68, and 0.94. Only the effect of moderately high physical activity was statistically significant. Analyses by type of activity revealed significant protective effects for women who reported the highest levels of cycling activities (adjusted odds ratio = 0.66, 95% confidence interval: 0.45, 0.97). These data do not suggest an inverse monotonic association between total physical activity and breast cancer risk in premenopausal women. The study prevalence of cycling and walking for transportation demonstrated that national habits need consideration in the exposure assessment.     

Indoor radon and lung cancer in France

BACKGROUND: Several case-control studies have indicated an increased risk of lung cancer linked to indoor radon exposure; others have not supported this hypothesis, partly because of a lack of statistical power. As part of a large European project, a hospital-based case-control study was carried out in 4 areas in France with relatively high radon levels. METHODS: Radon concentrations were measured in dwellings that had been occupied by the study subjects during the 5- to 30-year period before the interview. Measurements of radon concentrations were performed during a 6-month period using 2 Kodalpha LR 115 detectors (Dosirad, France), 1 in the living room and 1 in the bedroom. We examined lung cancer risk in relation to indoor radon exposure after adjustment for age, sex, region, cigarette smoking, and occupational exposure. RESULTS: We included in the analysis 486 cases and 984 controls with radon measures in at least 1 dwelling. When lung cancer risk was examined in relation to the time-weighted average radon concentration during the 5- to 30-year period, the estimated relative risks (with 95% confidence intervals) were: 0.85 (0.59-1.22), 1.19 (0.81-1.77), 1.04 (0.64-1.67), and 1.11 (0.59-2.09) for categories 50-100, 100-200, 200-400, and 400+ becquerels per cubic meter (Bq/m), respectively (reference <50 Bq/m). The estimated relative risk per 100 Bq/m was 1.04 (0.99-1.11) for all subjects and 1.07 (1.00-1.14) for subjects with complete measurements. CONCLUSIONS: Our results support the presence of a small excess lung cancer risk associated with indoor radon exposure after precise adjustment on smoking. They are in agreement with results from some other indoor radon case-control studies and with extrapolations from studies of underground miners.     

Case-control study of lung cancer among sugar cane farmers in India

OBJECTIVES: To investigate the risk of lung cancer among sugar cane farmers and sugar mill workers. METHODS: A case-control study was conducted based in six hospitals in the predominantly sugar cane farming districts of the province of Maharashtra in India. Newly diagnosed, histologically confirmed cases were identified from these hospitals between May 1996 and April 1998. Other cancers were chosen as controls and matched to cases by age, sex, district of residence, and timing of diagnosis. RESULTS: Adjusting for confounders, an increased risk of lung cancer was found for workers ever employed on a sugar cane farm (odds ratio (OR) 1.92, 95% confidence interval (95% CI) 1.08 to 3.40). Increased risks were found for work involving preparation of the farm (OR 1.81, 95% CI 0.99 to 3.27) and burning of the farm after harvesting (OR 1.82, 95% CI 0.99 to 3.34). Non-significant increases in risks were found for harvesting the crop (OR 1.41, 95% CI 0.70 to 2.90) and processing the cane in the mills (OR 1.70, 95% CI 0.20 to 12.60). CONCLUSIONS: Exposure to fibres of biogenic amorphous silica (BAS) formed from silica absorbed from the soil and deposited in the leaves of the sugar cane crop or crystalline silica formed as a result of conversion of BAS to cristobalite at high temperatures may account for the increased risks of lung cancer among sugar cane farmers.     

Case-control study on occupational exposure to diesel exhaust and lung cancer risk.

The association between lung cancer and occupations with probable exposure to diesel exhaust (DE) was studied among 2,584 cases and 5,099 hospital controls. The crude odds ratio (OR) for probable exposure was 1.31 (95% confidence interval [CI] 1.09-1.57), but adjustment for smoking and other confounders reduced the estimate to 0.95 (95% CI = 0.78-1.16). Similar results were observed for truck drivers, the only occupational category large enough for separate analysis. Data on self-reported exposure for 477 cases and 946 controls revealed a crude OR of 1.45 (95% CI = 0.93-2.27), which was reduced to 1.21 (95% CI = 0.78-2.02) after controlling for smoking and other confounders. The present results and a review of the literature do not definitively support an etiologic association between DE exposure and elevated lung cancer risk.     

Case-control study of bladder cancer and drinking water arsenic in the western United States

Numerous epidemiologic investigations have identified links between high concentrations of arsenic in drinking water and cancer, although the risks at lower exposures are largely unknown. This paper presents the results of a case-control study of arsenic ingestion and bladder cancer in seven counties in the western United States. These counties contain the largest populations historically exposed to drinking water arsenic at concentrations near 100 microg/liter. All incident cases diagnosed from 1994 to 2000 were recruited. Individual data on water sources, water consumption patterns, smoking, and other factors were collected for 181 cases and 328 controls. Overall, no increased risks were identified for arsenic intakes greater than 80 microg/day (odds ratio=0.94, 95% confidence interval: 0.56, 1.57; linear trend, p=0.48). These risks are below predictions based on high dose studies from Taiwan. When the analysis was focused on exposures 40 or more years ago, an odds ratio of 3.67 (95% confidence interval: 1.43, 9.42; linear trend, p<0.01) was identified for intakes greater than 80 microg/day (median intake, 177 microg/day) in smokers. These data provide some evidence that smokers who ingest arsenic at concentrations near 200 microg/day may be at increased risk of bladder cancer.     

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.