Homer Wilcox

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.

The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which “cases” have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and “controls” have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(8)1520–5)

Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study

PURPOSE Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. PATIENTS AND METHODS On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. RESULTS Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend) < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. CONCLUSION At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.

PHYTOESTROGEN CONSUMPTION AND ENDOMETRIAL CANCER RISK: A POPULATION-BASED CASE-CONTROL STUDY IN NEW JERSEY

Phytoestrogens have been shown to exert anti-estrogenic and estrogenic effects in some tissues, including the breast. However, only a few studies have evaluated their role in endometrial cancer risk. We evaluated this association in a population-based case–control study in New Jersey. A total of 424 cases and 398 controls completed an interview, including a food frequency questionnaire with supplemental questions for phytoestrogen foods. Risk estimates were derived using an unconditional logistic regression, adjusting for major risk factors for endometrial cancer. There was some suggestion of a decreased risk with quercetin intake (OR: 0.65; 95% CI: 0.41–1.01 for the highest compared to the lowest quartile; p for trend: 0.02). We found a limited evidence of an association with any of the lignans evaluated, total lignans, coumestrol, individual isoflavones, total isoflavones, or total phytoestrogens. However, there was some suggestion of an inverse association with total isoflavone intake limited to lean women (BMI <25; OR for the highest tertile: 0.50; 95% CI: 0.25–0.98) and those with a waist-to-hip ratio ≤0.85 (OR: 0.59; 95% CI: 0.33–1.05). There was no evidence of effect modification by HRT use. This study suggests a reduction in endometrial cancer risk with quercetin intake and with isoflavone intake in lean women.

Sun protection and skin self-examination in melanoma survivors

Objectives: Patients diagnosed with melanoma are at risk for developing recurrent and second primary disease. Skin self‐examination (SSE) and sun protection are standard clinical recommendations to minimize risk. In this study we examined performance of these behaviors in individuals with melanoma drawn from the general population.

Risk of Endometrial Cancer in Relation to Medical Conditions and Medication Use

We studied the relation of medical conditions related to obesity and medications used for these conditions with endometrial cancer. We also investigated the association of other medical conditions and medications with risk. This U.S. population-based case-control study included 469 endometrial cancer cases and 467 controls. Information on putative risk factors for endometrial cancer was collected through personal interviews. We asked women about their medical history and medications used for six months or longer and the number of years each medication was taken. Risk was strongly associated with increasing obesity (P for trend < 0.001). Among the conditions related to obesity, and after adjustment for age, body mass index, and other risk factors and conditions, uterine fibroids were independently related to an increased cancer risk [adjusted odds ratio (OR), 1.8; 95% confidence interval (95% CI), 1.2-2.5]. Although hypertension was not significantly related to endometrial cancer after adjustment for age and body mass index, the use of thiazide diuretics was independently associated with increased risk (OR, 1.8; 95% CI, 1.1-3.0). Anemia was associated with decreased risk (OR, 0.6; 95% CI, 0.5-0.9). Use of nonsteroidal anti-inflammatory drugs was related to a decreased risk (OR, 0.7; 95% CI, 0.5-0.97). To our knowledge, the observation about thiazide diuretics is novel and requires confirmation in other studies and populations. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1448–56)

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.

Associations of Cumulative Sun Exposure and Phenotypic Characteristics with Histologic Solar Elastosis

Background: Solar elastosis adjacent to melanomas in histologic sections is regarded as an indicator of sun exposure, although the associations of UV exposure and phenotype with solar elastosis are yet to be fully explored. Methods: The study included 2,589 incident primary melanoma patients with assessment of histologic solar elastosis in the population-based Genes, Environment, and Melanoma study. Ambient erythemal UV (UVE) at places of residence and sun exposure hours, including body site–specific exposure, were collected. We examined the association of cumulative site-specific and non–site-specific sun exposure hours and ambient UVE with solar elastosis in multivariable models adjusted for age, sex, center, pigmentary characteristics, nevi, and, where relevant, body site. Results: Solar elastosis was associated most strongly with site-specific UVE [odds ratio (OR) for top exposure quartile, 5.20; 95% confidence interval (95% CI), 3.40-7.96; P for trend <0.001] and also with site-specific sun exposure (OR for top quartile, 5.12; 95% CI, 3.35-7.83; P for trend <0.001). Older age (OR at >70 years, 7.69; 95% CI, 5.14-11.52; P for trend < 0.001) and having more than 10 back nevi (OR, 0.77; 95% CI, 0.61-0.97; P = 0.03) were independently associated with solar elastosis. Conclusion: Solar elastosis had a strong association with higher site-specific UVE dose, older age, and fewer nevi. Impact: Solar elastosis could be a useful biomarker of lifetime site-specific UV. Future research is needed to explore whether age represents more than simple accumulation of sun exposure and to determine why people with more nevi may be less prone to solar elastosis. Cancer Epidemiol Biomarkers Prev; 19(11); 2932–41. ©2010 AACR.

Adherence to the dietary guidelines for Americans and endometrial cancer risk

The Healthy Eating Index (HEI) was developed by the US Department of Agriculture with the goal of quantifying adherence to the Dietary Guidelines for Americans. The purpose of this study was to evaluate the impact of the HEI-2005 score and each of its components on endometrial cancer risk in a population-based case–control study in New Jersey. A total of 424 cases and 398 controls completed a Food Frequency Questionnaire, which was used to derive the HEI-2005 score. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression while adjusting for potential covariates, which included all major endometrial cancer risk factors. The adjusted OR for women in the highest quartile when compared to the lowest quartile was 0.83 (95% CI: 0.52–1.34). For the meat and beans component comprising meat, eggs, poultry, fish, and beans, the OR was 0.70 (95% CI: 0.45–1.11; p for trend: 0.07), with little evidence of an association with any of the individual foods. There was no indication of an association for any of the other components of the HEI or of effect modification by body mass index. This study suggested limited value for the HEI-2005 in predicting endometrial cancer risk.