a Field, R.W., a Lynch, C.F., b Steck, D.J., aSmith, B.J., aBrus, C.P., cNeuberger,
aWoolson, R.F., aFisher, E.F., d Platz,C.E., d Robinson, R.A.
of Public Health
University of Iowa
b Physics Department
St. Johns University
c Department of Preventive Medicine
University of Kansas School of Medicine
University of Iowa
The Iowa Radon Lung Cancer Study was a large-scale epidemiology study initiated in 1993 and funded by the National Institute of Environmental Health Sciences (NIEHS). The study assessed the risk posed by residential radon exposure. The 5-year study was performed in Iowa and the participants were women throughout Iowa who lived in their current home for at least 20 years. Over a thousand Iowa women took part in the study. Four hundred and thirteen of the participants were women who had developed lung cancer, the remaining 614 participants were controls who did not have lung cancer. The study was limited to women, because they historically tend to spend more time at home and they have less occupational exposure to other lung carcinogens.
The epidemiologic study was performed in Iowa for several reasons. Iowa has the highest average radon concentrations in the United States. In addition, women in Iowa tend to move less than most other states, which makes calculation of their past radon exposure easier. Iowa was also selected because it has a quality National Cancer Institute SEER cancer registry, which helped us identify women who developed lung cancer. Close to 60% of the basement measurements for both cases (participants with lung cancer) and controls (participants without lung cancer) exceeded the EPA's action level. Twenty-eight percent of the living areas for the controls and 33% of the living areas for the cases exceeded the EPA's action level of 4 pCi/L.
The study used the most advanced radon exposure measurement techniques ever performed in a residential radon study. Numerous yearlong radon measurements were made in each participant's home. Outdoor radon measurements were also performed in addition to estimates of work place exposure. All these measurements were linked to where the participants spent the proceeding 20 years in order to get a cumulative radon exposure.
The major paper reporting the findings was published in volume 151 of the American Journal of Epidemiology (pages 1081-1101) in 2000. The American Journal of Epidemiology is the premier scientific journal devoted to the publication of empirical research findings and methodologic developments in the field of epidemiologic research. Findings of the study were released to the press on May 25, 2000.
Risk estimates for the Iowa Radon Lung Cancer Study were adjusted for age, active smoking, and education. For all lung cancer subtypes, there was a positive categorical trend (p = 0.05). Analyses restricted to the live cases and controls noted both a strong categorical (p = 0.01) and continuous trend (p = 0.03). The Iowa Radon Lung Cancer Study's estimated excess odds at 11 WLM5-19 (roughly equivalent to a 15-year exposure at an average radon exposure of 4 pCi/L) averaged 0.50 for both all cases and the live case subset. For the all-case category, large cell carcinoma exhibited a statistically significant trend for both the continuous (p = 0.04) and categorical (p = 0.03) risk estimates. However, the differences in the linear excess odds between histologic types was not statistically significant (continuous p = 0.58, categorical p = 0.65). Overall, these results suggest that cumulative radon exposure is a significant risk factor for lung cancer in women.
The Iowa Radon Lung Cancer Study had several strengths. First, independent pathologic review was performed for 96 percent of the cases. Second, the study was carried out in Iowa, which has the highest mean radon concentrations in the United States. Third, the high radon concentrations in conjunction with a strict quality assurance protocol contributed to accurate and precise radon measurements. Fourth, the IRLCS criteria requiring occupancy in the current home for at least the last 20 years eliminated the need to impute radon measurements from missing homes. Fifth, the linkage between radon measurements and retrospective participant mobility allowed for a refined exposure estimate. The IRLCS risk estimates are in general agreement with the National Research Council's predicted cancer risk associated with indoor radon exposure. Overall, the risk estimates obtained in this study suggest that cumulative radon exposure in the residential environment is significantly associated with lung cancer risk.
THE IOWA and MISSOURI RESIDENTIAL RADON STUDIES
Phase II – Currently Underway
a College of Public Health
University of Iowa
b Physics Department
St. John's University
c National Cancer Institute
d Pacific Northwest National Laboratory
The specific aims of the 5-year Iowa and Missouri Residential Radon Studies (Phase-II), which initiated in 2000 are to: 1) further refine the estimated lung cancer risk posed by residential radon-222 (radon) decay product exposure using a novel glass-based retrospective radon decay product (progeny) reconstruction detector; 2) determine the shape (linear, quadratic, etc.) of the dose-response curve relating radon progeny exposure and lung cancer; 3) determine the lung cancer risk posed by radon progeny exposure for the various histologic types; and 4) examine the association between radon progeny and other lung cancer risk factors on the lung cancer incidence. The study, using state-of-the-art methods to measure retrospective radon progeny exposure, focuses on the association between residential radon progeny exposure and lung cancer.
Glass surfaces exposed to radon gas over an extended period of time are convenient radon progeny reservoirs that allow retrospective estimates of radon exposure. The novel glass-based detectors measure 210Pb previously embedded in glass through residual nuclei recoil implantation following alpha decay. Glass provides a stable matrix for the 210Pb deposit. The 22-year half-life of 210Pb means that it takes decades before the activity achieves an equilibrium value and the activity persists for years after exposure. This predictable temporal behavior provides a long-lasting marker for past radon and radon progeny concentrations in a home. Therefore, one can measure glass items that have been carried from home to home over long periods of time to estimate past residential radon progeny exposure. Because the radon progeny deliver the actual radiation dose to the lung tissues, rather than the radon gas itself, better residential radon progeny dose estimates require the reconstruction of actual airborne radon progeny concentrations. Pooling of data between two large-scale epidemiologic studies from a similar geographic area that used the glass-based detectors in addition to the contemporary radon gas detectors increases the power of the overall analyses. We anticipate the research will significantly reduce radon (more precisely radon progeny) exposure misclassification, which will enhance our ability to address the Specific Aims above.
The study design has three major components: 1) field calibration and laboratory validation of the retrospective radon detectors, 2) reanalysis of the risk estimates from the Iowa Radon Lung Cancer Study incorporating radon progeny exposure estimates obtained from retrospective radon detector (RRD) measurements, rather than radon gas measurements; 3) calculation of risk estimates from a pooled analyses of retrospective radon detectors exposure results for the previous National Institutes of Environmental Health Sciences (NIEHS) funded Iowa Radon Lung Cancer Study (IRLCS) and the National Cancer Institute (NCI) funded Missouri Radon Lung Cancer Study II (MRLCS-II).
Findings from the Iowa and Missouri Residential Studies have been published in over 25 peer-reviewed scientific journals. A few examples of some of the major findings follow.
Risk Estimates for Prolonged Residential Radon Exposure Risk estimates for the Iowa Radon Lung Cancer Study using estimates of retrospective gas exposure were adjusted for age, active smoking, and education. For all lung cancer subtypes, there was a positive categorical trend (p = 0.05). Analyses restricted to the live cases and controls noted both a strong categorical (p = 0.01) and continuous trend (p = 0.03). The Iowa Radon Lung Cancer Study's estimated excess odds at 11 WLM5-19 (roughly equivalent to a 15-year exposure at an average radon exposure of 4 pCi/L) averaged 0.50 for both all cases and the live case subset. Large cell carcinoma exhibited a statistically significant trend for both the continuous (p = 0.04) and categorical (p = 0.03) risk estimates, but the differences in the linear excess odds between histologic types was not statistically significant. These results suggest that cumulative radon exposure is a significant risk factor for lung cancer in women.
Improved Residential Radon Study Methodology – 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 and that previous epidemiologic investigations likely underestimated the risk posed by residential radon exposure.
State of the Art Radon and Radon Progeny Dosimetry - Radon progeny, rather than radon, deliver dose to the lungs during decade’s long exposures. The study has made advances in estimating contemporary and past radon progeny dose using passive integrating alpha detectors. Contemporary airborne radon and progeny activities are reconstructed from direct radon and surface deposited progeny measurements. Track registration material, with selected energy removing filters, detects the individual alpha emitting isotopic concentrations. These concentrations are used in a fate and transport model to calculate the available airborne dose rate. Retrospective radon progeny concentrations can be reconstructed from glass-implanted 210Po activity and the relationship between airborne and deposited activities determined from contemporary activities. Using a regression analysis of the IRLCS retrospective detector data to identify the important environmental variables, new detector modules, as well as the old, have been calibrated in controlled exposures. Active airborne progeny detectors are being developed and calibrated to directly sample the important environmental conditions and activities in a select group of homes to improve and validate the dose estimates.
Diet and Lung Cancer - When comparing the fifth (highest) to the first (lowest) quintile of consumption of total fat, saturated fat and cholesterol in the IRLCS, we obtained odds ratios of 2.0 (1.3-3.1), 3.0 (1.9-4.7), and 2.0 (1.3-3.0), respectively for lung cancer. However, when red meat was entered into the model along with total fat, saturated fat or cholesterol, the excess risk for the macronutrients disappeared while an odds ratio of 3.3 (1.7-7.6) was obtained for red meat. The odds ratios for red meat consumption were similar among adenocarcinoma cases, OR=3.0 (1.1-7.9) and non-adenocarcinoma cases, OR=3.2 (1.3-8.3) and among life-time nonsmokers and ex-smokers OR=2.8 (1.4-5.4), and current smokers, OR=4.9 (1.1-22.3). Yellow-green vegetables were protective with an odds ratio of 0.4 (0.2-0.7). We concluded that consumption of red meat was associated with an increased risk of lung cancer even after controlling for total fat, saturated fat, cholesterol, fruit, yellow-green vegetable consumption and smoking history, while yellow-green vegetables are associated with a decreased risk of lung cancer.
Gene Environment Interactions – Recent work with collaborators at the NCI and City of Hope (Los Angeles) have explored gene-environment interactions between residential radon, environmental tobacco smoke (ETS), and the GSTM1 null genotype. The sample series included lung cancer cases pooled from three previously completed case-control studies. Recent results show a statistically significant 3-fold increase in the interaction OR for GSTM1 null cases compared with GSTM1 present cases. In addition, the ETS and GSTM1 interaction OR was significantly elevated over two-fold. This is the first study to provide evidence of a radon and GSTM1 interaction in risk of lung cancer and supports the hypothesis that radon and ETS may promote neoplasia by damaging genetic pathways that include GSTM1. These findings have just been submitted for publication.
Laboratory calibration of the retrospective radon progeny detector is nearing completion and field validation studies are planned for fall of 2004. As soon as this work is complete, we will perform a reanalysis of the IRLCS data using the glass-based retrospective radon progeny data. Next, we will pool the glass-based retrospective radon progeny data from both the IRLCS and MRLCS. The pooled data should allow more power to examine the lung cancer risk posed by residential radon decay product exposure and determine whether the risk varies by histologic type. We are also continuing our collaboration with European investigators pooling the findings from all the residential radon studies that have used standard radon gas measurements and plan an eventual pooling of residential radon studies that incorporated the use of the more advanced glass-based measurements. Further collaborations are also underway with researchers at NCI and City of Hope (Los Angeles) to explore additional studies examining gene-environment interactions and lung cancer. We have archived paraffin fixed tumor specimens from the Iowa Radon Lung Cancer Study and welcome the opportunity of additional collaborations using these materials. We are also interested in performing future studies in Iowa, with the cooperation of the NCI SEER Iowa Cancer Registry, examining the impact of environmental causes of lung cancer in relation to energy balance in never-smoking individuals.
Selected Peer-Reviewed Scientific Publications from the Iowa Residential Radon Study and On-going NCI-Sponsored Iowa and Missouri Residential Radon Studies
For additional information on these studies contact:R. William Field, M.S., Ph.D.
GENERAL RADON INFORMATION
Notes: This will download the powerpoint presentation to your computer. You will need Microsoft powerpoint to open/see the presentation. If you are having trouble, sometimes it is best to select the option 'Save file' when prompted, open powerpoint, and then open the downloaded file (CRCPDweb.ppt). In our tests, both Firefox and MS Internet Explorer browsers running on a Windows XP machine and the latest version of Microsoft office had no problem downloading and viewing the file. The file size is 2.14 MB. The full file path is http://www.cheec.uiowa.edu/misc/CRCPDweb.ppt
Notes: This will download the powerpoint presentation to your computer. You will need Microsoft powerpoint to open/see the presentation. If you are having trouble, sometimes it is best to select the option 'Save file' when prompted, open powerpoint, and then open the downloaded file (Webtop10.ppt). In our tests, both Firefox and MS Internet Explorer browsers running on a Windows XP machine and the latest version of Microsoft office had no problem downloading and viewing the file. The file size is 2.78 MB. The full file path is http://www.cheec.uiowa.edu/misc/Webtop10.ppt
Acknowledgements: We thank the National Institutes of Health: National Cancer Institute and National Institute of Environmental Health Sciences , Center for Health Effects of Environmental Contamination at the University of Iowa, Iowa Cancer Registry, and the participants and their caring families that made these studies possible.