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 a-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 a-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 a-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.

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 x time), its exposures estimates are presented in the form WLM(5-19) (Field et al., 2000a). WLM(5-19) represents the working level months for exposures that occurred 5-19 yr prior to diagnosis for cases or time of interview for control. Eleven WLM(5-19) is approximately equivalent to an average residential radon exposure of 4 pCi/L for 15 yr, assuming a 70% home occupancy.

Cancer incidence in adolescents and young adults in the United States, 1992-1997.

PURPOSE: To examine cancer incidence patterns among adolescents and young adults in the United States. METHODS: Cancer incidence data from 26 population-based central cancer registries for 1992-1997 were used. Individual cancers were grouped into specific diagnostic groups and subgroups using an integrated classification scheme. The integrated scheme was developed for this study and was based on the most commonly used schemes in population-based epidemiologic studies: Surveillance, Epidemiology, and End Results Program's site groups, International Classification of Childhood Cancer, and International Agency for Research on Cancer's Histological Groups for Comparative Studies. Percent distributions and age-specific incidence rates per million population were computed for adolescents (aged 15-19 years) and young adults (aged 20-24 years) by gender. RESULTS: The data for 26,010 cancer cases were examined. Among 15-19-year-olds, the five most common cancers were Hodgkin's disease, leukemia, cancer in the brain and other nervous system, bone cancer, and non-Hodgkin's disease. Among 20-24-year-olds, the five most common cancers were Hodgkin's disease, testicular cancer, thyroid cancer, melanoma of the skin, and leukemia. The proportions and rates of the histologic subtypes for most of the common cancers changed with advancing age. For example, among 15-19-year-olds, acute lymphocytic leukemia accounted for approximately 60% of leukemias in males and 50% in females. Among 20-24-year-olds, however, the corresponding percentages of acute lymphocytic leukemia were 37% in males and 31% in females. For ovarian cancer, the germ cell tumor was the most common subtype (54.6% of all ovarian cancers) among 15-19-year-olds. In contrast, ovarian carcinoma was the predominant subtype (70.4%) among 20-24-year-olds. For both age groups, the incidence rates of nodular Hodgkin's disease, melanoma of the skin, and thyroid cancer were significantly greater in females than in males. CONCLUSIONS: Cancer incidence patterns among adolescents and young adults are distinctive. In these age groups, a transition from predominantly pediatric histologic subtypes to adult subtypes was observed for Hodgkin's disease, leukemia, ovarian cancer, and soft tissue sarcoma. Gender differences were found for Hodgkin's disease, melanoma of the skin, and thyroid cancer.

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.

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

OBJECTIVE: Melanoma 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.