Judith B. Klotz

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 α-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.

A Combined Analysis of North American Case-Control Studies of Residential Radon and Lung Cancer

Cohort studies have consistently shown underground miners exposed to high levels of radon to be at excess risk of lung cancer, and extrapolations based on those results indicate that residential radon may be responsible for nearly 10–15% of all lung cancer deaths per year in the United States. However, case-control studies of residential radon and lung cancer have provided ambiguous evidence of radon lung cancer risks. Regardless, alpha-particle emissions from the short-lived radioactive radon decay products can damage cellular DNA. The possibility that a demonstrated lung carcinogen may be present in large numbers of homes raises a serious public health concern. Thus, a systematic analysis of pooled data from all North American residential radon studies was undertaken to provide a more direct characterization of the public health risk posed by prolonged radon exposure. To evaluate the risk associated with prolonged residential radon exposure, a combined analysis of the primary data from seven large scale case-control studies of residential radon and lung cancer risk was conducted. The combined data set included a total of 4081 cases and 5281 controls, representing the largest aggregation of data on residential radon and lung cancer conducted to date. Residential radon concentrations were determined primarily by α-track detectors placed in the living areas of homes of the study subjects in order to obtain an integrated 1-yr average radon concentration in indoor air. Conditional likelihood regression was used to estimate the excess risk of lung cancer due to residential radon exposure, with adjustment for attained age, sex, study, smoking factors, residential mobility, and completeness of radon measurements. Although the main analyses were based on the combined data set as a whole, we also considered subsets of the data considered to have more accurate radon dosimetry. This included a subset of the data involving 3662 cases and 4966 controls with α-track radon measurements within the exposure time window (ETW) 5–30 yr prior to the index date considered previously by Krewski et al. (2005). Additional restrictions focused on subjects for which a greater proportion of the ETW was covered by measured rather than imputed radon concentrations, and on subjects who occupied at most two residences. The estimated odds ratio (OR) of lung cancer generally increased with radon concentration. The OR trend was consistent with linearity (p = .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95% confidence limits (−0.01, 0.26). For the subset of the data considered previously by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our criteria (residential stability and completeness of radon monitoring) expected to improve radon dosimetry led to increased estimates of the EOR. For example, for subjects who had resided in only one or two houses in the 5–30 ETW and who had α-track radon measurements for at least 20 yr of this 25-yr period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward extrapolation of the miner data. Collectively, these results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted by extrapolation of results from occupational studies of radon-exposed underground miners. E. G. Létourneau and J. B. Schoenberg have retired; J. A. Stolwijk holds an emeritus position. We acknowledge the helpful input of the following individuals who served on the International Steering Committee for the North American combined analysis: Ken Chadwick (CEC Radiation Protection Program), Susan Conrath (U.S. Environmental Protection Agency), Sarah Darby (Oxford University), Evan Douple (U.S. National Academy of Sciences), Colin Muirhead (UK National Radiation Protection Board), and Susan Rose (U.S. Department of Energy). Salary support for Drs. Field, Lynch, and Steck was provided in part by grant numbers R01 ES05653 and P30 ES05605 from the National Institute of Environmental Health Sciences, NIH and grant number R01 CA85942 from the National Cancer Institute, NIH. This research was supported by grants from the Canadian Institutes of Health Research (formerly the Medical Research Council of Canada) and the Natural Sciences and Engineering Research Council of Canada to D. Krewski, who currently holds the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. Financial support for the meetings of the Analysis Team and the Steering Committee was also provided by Health Canada and the U.S. Department of Energy. We are grateful to Dr. Huixia Jiang for assistance with the combined analysis, and to Jackie Monaghan for technical assistance in preparing this report.

Neural tube defects and drinking water disinfection by-products.

We have examined data from 12 epidemiologic studies for quantitative evidence of biologic synergy between asbestos and smoking on lung cancer risks. Estimates of the effect associated with joint exposure to the two agents exceeded the sum of their separate effects in each study. We explored the vari

An Overview of the North American Residential Radon and Lung Cancer Case-Control Studies

Lung cancer has held the distinction as the most common cancer type worldwide since 1985 (Parkin et al., 1993). Recent estimates suggest that lung cancer accounted for 1.2 million deaths worldwide in 2002, which represents 17.6% of the global cancer deaths (Parkin et al., 2005). During 2002, the highest lung cancer rates for men worldwide reportedly occurred in North America and Eastern Europe, whereas the highest rates in females occurred in North America and Northern Europe (Parkin et al., 2005). While tobacco smoking is the leading risk factor for lung cancer, because of the magnitude of lung cancer mortality, even secondary causes of lung cancer present a major public health concern (Field, 2001). Extrapolations from epidemiologic studies of radon-exposed miners project that approximately 18,600 lung cancer deaths per year (range 3000 to 41,000) in the United States alone are attributable to residential radon progeny exposure (National Research Council, 1999). Because of differences between the mines and the home environment, as well as differences (such as breathing rates) between miners and the general public, there was a need to directly evaluate effects of radon in homes. Seven major residential case-control radon studies have been conducted in North America to directly examine the association between prolonged radon progeny (radon) exposure and lung cancer. Six of the studies were performed in the United States including studies in New Jersey, Missouri (two studies), Iowa, and the combined states study (Connecticut, Utah, and southern Idaho). The seventh study was performed in Winnipeg, Manitoba, Canada. The residential case-control studies performed in the United States were previously reviewed elsewhere (Field, 2001). The goal of this review is to provide additional details regarding the methodologies and findings for the individual studies. Radon concentration units presented in this review adhere to the types (pCi/L or Bq/m3) presented in the individual studies. One picocurie per liter is equivalent to 37 Bq/m3. Because the Iowa study calculated actual measures of exposure (concentration × time), its exposures estimates are presented in the form WLM5–19 (Field et al., 2000a). WLM5–19 represents the working level months for exposures that occurred 5–19 yr prior to diagnosis for cases or time of interview for control. Eleven WLM5–19 is approximately equivalent to an average residential radon exposure of 4 pCi/L for 15 yr, assuming a 70% home occupancy. Ernest G. Létourneau and Janet B. Schoenberg are retired; Jan A. Stolwijk has emeritus status. Salary support for Drs. Steck and Field was provided in part by grant numbers R01 ES05653 and P30 ES05605 from the National Institute of Environmental Health Sciences, NIH and grant number R01 CA85942 from the National Cancer Institute, NIH.

Familial aggregation of melanoma risks in a large population-based sample of melanoma cases.

ObjectiveMelanoma has been shown in numerous studies to be associated with sun exposure, and with host phenotypic factors of genetic origin. In this study we use information from a large series of incident cases of melanoma from an international population-based study to examine the patterns of incidence of melanoma in the first-degree relatives of these cases. Methods: A total of 2508 incident cases of melanoma provided information on basic demographic data and pigmentary characteristics, in addition to detailed information on family history of melanoma. These data were used to examine the incidence rates ratios of melanoma in the relatives of cases in relation to population rates, and also with respect to phenotypic characteristics of the probands that have been shown to be associated with melanoma: mole counts, hair color, eye color, and skin sensitivity to the sun. Results: The incidence rates reflect the underlying patterns of incidence in the source populations, with generally higher rates in the Australian sample, low rates in Italy, and intermediate rates in the USA and Canada. Also, rates are higher in men than in women, except at very young ages. Phenotypic characteristics of the probands were only weakly associated with the observed rates in the relatives although there is a strong inverse association with age at diagnosis. Cumulative risk of melanoma rises to 6.9 (6.1) at age 80 in male (female) first-degree relatives of cases, and to 10.8 (9.5) in relatives of cases diagnosed before age 50. Conclusions: Relatives of cases diagnosed with melanoma are at considerable lifetime risk of the disease, especially if the case is diagnosed at a young age.