Environmental Risk Factors for Lung Cancer Mortality in the Cancer Prevention Study-II

Background: Case–control studies conducted in North America, Europe, and Asia provided evidence of increased lung cancer risk due to radon in homes. Here, the association between residential radon and lung cancer mortality was examined in a large-scale cohort study. Methods:Nearly 1.2 million Cancer Prevention Study-II participants were recruited in 1982. Mean countylevel residential radon concentrations were linked to study participants according to ZIP code information at enrollment [mean (SD)1⁄4 53.5 Bq/m (38.0)]. Cox proportional hazards regressionmodels were used to obtain adjusted HR and 95% CI for lung cancer mortality associated with radon. Potential effect modification by cigarette smoking, ambient sulfate concentrations, and other risk factors was assessed on both the additive and multiplicative scales. Results: Through 1988, 3,493 lung cancer deaths were observed among 811,961 participants included in the analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (P 1⁄4 0.02). A 15% (95% CI, 1–31) increase in the risk of lung cancer mortality was observed per 100 Bq/m increase in radon. Participants with mean radon concentrations above the EPA guideline value (148 Bq/m) experienced a 34% (95% CI, 7–68) increase in risk for lung cancer mortality relative to those below the guideline value. Conclusions: This large prospective study showed positive associations between ecological indicators of residential radon and lung cancer. Impact: These results further support efforts to reduce radon concentrations in homes to the lowest possible level. Cancer Epidemiol Biomarkers Prev; 20(3); 438–48. 2011 AACR. Introduction Lung cancer is the leading cause of cancer mortality in the United States. In 2009, it was estimated that a total of 219,440 new lung cancer cases and 159,390 deaths occurred (1). Lung cancer is a highly fatal disease, with a 5-year survival ratio of 15% (1). Although incidence rates for lung cancer have been declining for males, they are only now leveling off after several decades of increase for females, most likely because of changes in cigarette smoking patterns in recent decades (1). Although the majority of lung cancer cases can be attributed to active cigarette smoking, residential radon and ambient air pollution also have been implicated as important risk factors for this disease in the general population (2–5). Radon gas is formed during the radioactive decay of uranium-238, which is naturally present in rocks and soils in the environment. In 1988, the International Agency for Research on Cancer (IARC) determined that radon was a cause of human lung cancer, based on studies of underground miners historically exposed to high levels of the gas (2). It was also observed that a-particles emitted from radon decay products can damage DNA in human lung tissue (2). Bonner and colleagues (6) recently reported an interaction between glutathione-S-transferase M1 and radon, suggesting that radonmay also induce lung cancer through oxidative mechanisms. Radon gas enters homes through cracks and other openings in the foundation and accumulates largely in the basement and lower living areas (7). Although there have been more than 20 case–control studies examining the association between residential radon and lung Authors' Affiliations: Graduate and Postdoctoral Studies, McLaughlin Center for Population Health Risk Assessment, Institute of Population Health, and Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa; Risk Sciences International, Ottawa, Ontario, Canada; Department of Economics, Brigham Young University, Provo, Utah; and Epidemiology Research Program, American Cancer Society, Atlanta, Georgia Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). Corresponding Author: Michelle C. Turner, McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, One Stewart Street, Room 313, Ottawa, Ontario, Canada K1N 6N5. Phone: 613-562-5800 ext. 2328; Fax: 613-562-5380. E-mail: mturner@uottawa.ca doi: 10.1158/1055-9965.EPI-10-1153 2011 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention Cancer Epidemiol Biomarkers Prev; 20(3) March 2011 438 American Association for Cancer Research Copyright © 2011 on March 8, 2011 cebp.aacrjournals. org Downloaded from Published OnlineFirst January 6, 2011; DOI:10.1158/1055-9965.EPI-10-1153