Short Communication: Radon testing via a state tobacco quitline.

Objective: Exposure to radon gas at home is the second largest cause of lung cancer after smoking and dramatically increases smokers' risk of lung cancer. State tobacco quitlines are uniquely positioned to inform smokers about radon, yet, to our knowledge, none does so. We explored the feasibility of introducing free radon tests via the tobacco quitline in North Dakota, a state with one of the highest radon levels in the U.S. Methods: Five hundred consecutive callers to the ND Quits Tobacco quitline from February 2021 to February 2023 were invited to complete a brief radon questionnaire and receive a free radon test kit. Radon tests were bar-coded so that the return rate of the tests and the radon levels could be determined. Results: Two hundred fifty-one (51 %) callers completed the questionnaire and seventy-five radon tests were successfully returned to the laboratory. More than one third of the test results were ≥ 4.0 pCi/L, the action level recommended by the EPA. Only 1 in 5 participants reported knowing that radon caused lung cancer. Conclusion: Radon knowledge among ND smokers is poor. Radon test distribution via quitlines is feasible and may be a valuable addition to quitline services, particularly in states with high radon levels.

Radon Exposure and Incident Stroke Risk in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States. METHODS: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics. RESULTS: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L (p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses. DISCUSSION: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. METHODS: We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. RESULTS: The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. DISCUSSION: The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

Comparing Communication Methods to Increase Radon Knowledge and Home Testing: A Randomized Controlled Trial in a High-Radon City.

INTRODUCTION: Exposure to residential radon is a preventable cause of cancer. Prevention requires testing, but the percentage of homes that have been tested is small. One reason for the low testing rates may be that printed brochures fail to motivate people to obtain and return a radon test. METHODS: We developed a radon app for smartphones that contained the same information as printed brochures. We conducted a randomized, controlled trial that compared the app to brochures in a population comprised largely of homeowners. Cognitive endpoints included radon knowledge, attitudes toward testing, perceived severity and susceptibility to radon, and response and self-efficacy. Behavioral endpoints were participants' requests for a free radon test and the return of the test to the lab. Participants (N = 116) were residents of Grand Forks, North Dakota, a city with one of the nation's highest radon levels. Data were analyzed by general linear models and logistic regression. RESULTS: Participants in both conditions showed significant increases in radon knowledge (p < 0.001), perceived susceptibility (p < 0.001), and self-efficacy (p = 0.004). There was a significant interaction, with app users showing greater increases. After controlling for income, app users were three times more likely to request a free radon test. However, contrary to expectation, app users were 70% less likely to return it to the lab (p < 0.01). CONCLUSIONS: Our findings confirm the superiority of smartphones in stimulating radon test requests. We speculate that the advantage of brochures in promoting test returns may be due to their ability to serve as physical reminders.

Interventions to promote home radon testing: A randomized clinical trial of a smartphone app vs. printed brochures.

Radon is a preventable cause of lung cancer, but the percentage of homes tested for radon is low. We previously developed a smartphone app that informs users about radon and allows them to request a free radon test. Here we conducted a randomized, controlled trial comparing the radon app versus printed brochures on radon knowledge, attitudes, and behaviors, including the proportion of participants requesting radon tests. Participants (N = 138) were undergraduates at a midwestern university. Data were analyzed by t-tests, general linear models, and logistic regression. App users showed significantly greater increases in radon knowledge (p = 0.010) and self-efficacy (p < 0.001) and requested tests three times more often than brochure recipients (41.4% vs. 13.2%, p < 0.001). However, the rate of test usage in each condition was low, ~3%. In conclusion, the radon app markedly outperformed brochures in increasing knowledge and requests for radon tests. Future work should focus on methods to increase test usage.

Criterion Validity of Radon Test Values Reported by a Commercial Laboratory versus the Environmental Protection Agency.

Objective: Radon exposure is a proven cause of lung cancer and is a possible cause of other diseases. Recently, several ecologic studies explored the correlation of county-wide incidence rates for non-lung cancers with residential radon levels, using radon data reported by a commercial laboratory. However, the validity of the commercial radon data, i.e., whether they are an accurate representation of the radon levels in the counties from which they were drawn, is unknown. Methods: We compared county-wide radon data from the commercial laboratory with corresponding measurements from the same counties reported previously by the Environmental Protection Agency (EPA). Matching data were available for four states, Iowa, North Dakota, Texas, and Wisconsin, and were compared by paired t-tests. Criterion validity of the commercial tests, i.e., how well the commercial data predicted the EPA data, was tested using non-parametric methods, Kendall's tau, Lin's concordance, and Passing−Bablok regression. Results: The commercial and EPA data pairs from the four states were significantly positively correlated, although the size of the correlations was modest (tau = 0.490, Lin = 0.600). Passing−Bablok regression indicated that the commercial radon values were significantly higher than their EPA pairs and significantly overestimated radon at low levels (<4 pCi/L, p < 0.001). Conclusions: The commercial laboratory data were moderately predictive of EPA radon levels at the county level but were significantly biased upwards at low levels. The disagreement likely has several causes, including selection bias from homes that were tested voluntarily. Ecologic studies that employ radon data obtained from commercial laboratories should be interpreted with caution.

Lead service lines and Parkinson's disease prevalence in U.S. States.

INTRODUCTION: We recently showed that the prevalence of Parkinson's Disease (PD) in U.S. states is positively associated with the quantity of acid rain. Acid rain could play an etiologic role in PD by mobilizing metals, e.g., lead, from watersheds and pipes into drinking water. We assessed the correlation of PD with lead service lines, the underground pipes that connect homes to municipal water sources, which are a major aqueous source of lead. METHODS: We used multiple regression techniques to examine PD prevalence rates by state relative to the number of lead service lines. We included known or suspected aqueous risk factors, e.g., the Acid Precipitation Index (a measure of acid rain) and well water use. RESULTS: Age-, race-, and sex-adjusted prevalence rates for PD were significantly and positively correlated with the log number of lead service lines (p = 0.0004). The effect of lead service lines remained significant after adjusting for the effects of acid rain and well water use (p = 0.0019). CONCLUSION: These findings are consistent with a role for lead in the etiology of PD. Studies of lead service line exposure in relation to PD at the individual level are warranted.

Acid Precipitation and the Prevalence of Parkinson's Disease: An Ecologic Study in U.S. States.

Although the etiology of Parkinson's disease (PD) is unknown, potentially informative clues lie in its geographic distribution. PD prevalence rates within the U.S. are significantly higher in the Midwest and Northeast, a pattern that resembles the geographic distribution of acid precipitation ("acid rain"). Using linear and multivariable regression, we examined state-wide data on PD prevalence in relation to environmental factors including total precipitation, the acidity of precipitation, the use of well water, and industrial releases of sulfuric acid. In multivariate analyses, age-, race-, and gender-adjusted prevalence rates for PD were inversely correlated with well water use and positively correlated with industrial releases of sulfuric acid and with the quantity of acid precipitation (p < 0.0001). To our knowledge, this is the first report of an association between PD and acid rain. Because acid rain is known to leach metals from soils and pipes into drinking water, acid rain's association with PD prevalence adds support for a role for metals in the etiology of PD.

Radon Knowledge and Practices Among Family Physicians in a High Radon State.

BACKGROUND: Exposure to radon at home is the largest cause of lung cancer after smoking, and the combination of smoking and radon increases lung cancer risk several-fold. North Dakota has some of the highest residential radon levels in the United States. Although family physicians in North Dakota commonly counsel patients about smoking cessation, little is known about their knowledge and practices concerning radon. METHODS: We mailed a questionnaire to 350 North Dakota family physicians regarding radon knowledge, beliefs, their own radon testing, and radon counseling of patients. The responses were analyzed by descriptive statistics, analysis of variance, and logistic regression. RESULTS: Sixty-one percent of the surveys were completed. Seventy percent of family physicians correctly identified radon as radioactive; 67% reported that they do not inform patients about radon; and 80% reported never discussing the combined hazards of radon and smoking. Conversely, 35% of family physicians reported that they tested their own homes for radon. DISCUSSION: Most North Dakota family physicians are knowledgeable about radon, and more than one third have tested their own homes. However, only a minority transmit this knowledge to their patients. Future efforts should educate physicians about communicating radon risks, especially in conjunction with smoking.

Brain cancer incidence rates and the presence of nuclear reactors in US states: a hypothesis-generating study.

BACKGROUND: The etiology of brain cancer is poorly understood. The only confirmed environmental risk factor is exposure to ionizing radiation. Because nuclear reactors emit ionizing radiation, we examined brain cancer incidence rates in the USA in relation to the presence of nuclear reactors per state. METHODS: Data on brain cancer incidence rates per state for Whites by sex for three age groups (all ages, 50 and older, and under 50) were obtained from cancer registries. The location, number, and type of nuclear reactor, i.e., power or research reactor, was obtained from public sources. We examined the association between these variables using multivariate linear regression and ANOVA. RESULTS: Brain cancer incidence rates were not associated with the number of nuclear power reactors. Conversely, incidence rates per state increased with the number of nuclear research reactors. This was significant for both sexes combined and for males in the 'all ages' category (ß = 0.08, p = 0.0319 and ß = 0.12, p = 0.0277, respectively), and for both sexes combined in the'50 and older' category (ß = 0.18, p = 0.0163). Brain cancer incidence rates for counties with research reactors were significantly higher than the corresponding rates for their states overall (p = 0.0140). These findings were not explicable by known confounders. CONCLUSIONS: Brain cancer incidence rates are positively associated with the number of nuclear research reactors per state. These findings merit further exploration and suggest new opportunities for research in brain cancer epidemiology.

Women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin. A longitudinal study in the Janus Serum Bank Cohort.

BACKGROUND: Ovarian cancer is associated with high serum calcium and low serum albumin in clinical and epidemiologic studies. Whether high calcium and low albumin predispose to ovarian cancer or reflect existing cancer is unclear. OBJECTIVE: Test the hypothesis that serum calcium increases and serum albumin decreases in women who develop ovarian cancer. METHODS: Two hundred and four women donated sera to the Janus Serum Bank in Norway pre- and post-diagnosis of ovarian cancer, donations separated by approximately 14 years. We measured calcium and albumin in these sera and calculated the albumin-corrected calcium. Sera were adjusted for patient age and storage time. RESULTS: Post-diagnosis, mean age- and storage-adjusted calcium increased, from 2.53 to 2.68 mmol/L (p < .001). Mean age- and storage-adjusted, albumin-corrected calcium increased from 2.3 to 2.7 mmol/L (p < .001). Conversely, mean age- and storage-adjusted albumin decreased, from a mean of 51.3 to 40.9 g/L (p < .001). Significant changes were observed in women with early stage and metastatic cancer. CONCLUSIONS: These data support the hypothesis that calcium and albumin are serum biomarkers of extant ovarian cancer. Longitudinal changes in calcium and albumin may be useful in ovarian cancer early detection.

Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020.

PURPOSE: This ecological analysis investigates the spatial patterns of the COVID-19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID-19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state-level measure of the percent of the population that has been tested for COVID-19 was used to control for the impact of testing. FINDINGS: The impact of COVID-19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID-19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID-19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to "shelter-in-place" should continue to stem the spread of COVID-19.

Communicating radon risk via a smartphone app: a pilot intervention study.

BACKGROUND: Residential radon is a major preventable cause of lung cancer. However, prevention requires radon testing and it has proven very challenging to motivate individuals to test their homes for hazards like radon that are invisible and whose health effects occur after a long latency following exposure. Novel approaches to radon communication are urgently needed. METHODS: We created a novel radon-education app for smartphones and examined its effectiveness in increasing radon knowledge and radon testing. We studied radon knowledge and attitudes and behavior relevant to radon testing before and after app use. RESULTS: Ninety-seven undergraduates installed the app on their smartphones and used it for a month. App use resulted in higher scores in the domains of radon knowledge (p < .001); self-efficacy (p < .001), and response efficacy (p < .001). Twenty-three participants (24%) used the app to obtain a free radon test kit. Self-efficacy (p < .05) and response efficacy (p < .01) were positive predictors of ordering a test kit. The test process completion rate (the fraction of participants who ordered test kits, used them to test their houses and sent the kits to the lab) was 9%. CONCLUSIONS: A smartphone app is a promising venue for communicating radon risk and for stimulating radon testing. Future interventions designed to increase actual test kit use are required to maximize the benefit of the app.

Thyroid Cancer Incidence Rates in North Dakota are Associated with Land and Water Use.

Objective: The increasing rate of thyroid cancer diagnoses in the U.S. reflects the increasing use of ultrasonography and of specialist medical care. North Dakota is a rural state with limited access to specialist care, yet its incidence of thyroid cancer is significantly greater than that of the U.S. overall. We sought to identify factors responsible for the high incidence of thyroid cancer in North Dakota. Methods: We examined county-specific incidence rates for thyroid cancer in North Dakota in relation to demographic and geographic factors, including median household income, percent of land fertilized, cattle density per capita, and source of drinking water (city or well water), using structural equation modeling. We included county level data on residential radon levels and estimates of radioactive iodine in milk following nuclear weapons testing in the 1950s. Results: Thyroid cancer incidence rates were significantly associated with median income (p < 0.05); percent of land fertilized (p < 0.05); the use of city water (p < 0.01), and cattle density per capita (p < 0.001). Conclusions: The risk of thyroid cancer in North Dakota is positively associated with income and with factors related to land and water use. Our finding that thyroid cancer incidence rates are associated with the use of city water was unexpected and merits examination in other locations with a mix of city and well water use.

Serum 25-hydroxyvitamin D levels predict cancer survival: a prospective cohort with measurements prior to and at the time of cancer diagnosis.

PURPOSE: Circulating 25-hydroxyvitamin D (25-OHD) levels have been inversely associated with cancer death, but the nature of this relationship is unclear. We investigated this association using repeated measurements of serum 25-OHD. PATIENTS AND METHODS: Pre-diagnostic serum samples were collected in population health surveys in Norway (1973-2004). Participants who subsequently developed cancer (1984-2004) provided a second serum sample at the time of cancer diagnosis. Samples were stored in the Janus Serum Bank. Repeated samples existed from 202 breast cancers, 193 lung cancers, 124 lymphomas, and 37 colon cancers. Serum 25-OHD was measured via competitive radioimmunoassay. Cox regression models assessed associations between 25-OHD and cancer-specific death (case fatality) through 2012, given as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The median time between pre-diagnostic and diagnostic samples was 14.4 years. The median 25-OHD levels were 63.3 and 62.5 nmol/L, respectively. During follow-up, 313 cancer deaths occurred. Compared to low pre-diagnostic 25-OHD levels (<46 nmol/L), higher levels (≥46 nmol/L) had significantly lower HRs (39-54%) of case fatality. This result was also seen for the diagnostic samples. Donors who had both samples at high (≥62 nmol/L) levels had 59% lower HR of case fatality, compared to those for whom both samples were at low levels (<46 nmol/L). Furthermore, versus a decline in serum 25-OHD (median -22.4 nmol/L) from pre-diagnostic to diagnostic samples, a rise (median 22.3 nmol/L) was associated with lower case fatality (HR 0.57, 95% CI 0.43-0.75). CONCLUSION: Our findings suggest a causal relationship between vitamin D and cancer case fatality.

An exploration of colorectal cancer incidence rates in North Dakota, USA, via structural equation modeling.

PURPOSE: The state of North Dakota has one of the highest incidence rates for colorectal cancer in the USA. Its high incidence rate, coupled with a large variation in incidence rates among counties within the state, makes North Dakota a "natural laboratory" in which to investigate environmental clues to colorectal cancer. We conducted a hypothesis-generating study to explore potential determinants of colorectal cancer in North Dakota. METHODS: We obtained county-specific incidence rates for North Dakota's 53 counties from the statewide cancer registry and corresponding data on county demographic, agricultural, and geophysical features from population-based sources. Candidate demographic/agricultural variables included median household income, population density, colorectal cancer screening rates, average farm size (in acres), and the percent of county fertilized. Geophysical variables included the uranium content of soil, residential radon levels, and source of drinking water (municipal or well water). Statistical analyses were performed via multivariate regression and structural equation modeling. RESULTS: Colorectal cancer incidence rates across North Dakota counties varied 3-fold. The structural equation model identified a significant role for well water use (p < 0.05). This finding is consistent with studies that implicate well water in colorectal cancer. CONCLUSIONS: Well water contains several agents, e.g., bacteria, disinfection by-products, and nitrates that are potent colorectal carcinogens. Studies of well water use and colorectal cancer risk at the individual level in North Dakota are warranted.

Ovarian Cancer Incidence in the U.S. and Toxic Emissions from Pulp and Paper Plants: A Geospatial Analysis.

Ovarian cancer is the fifth leading cause of female cancer mortality in the U.S. and accounts for five percent of all cancer deaths among women. No environmental risk factors for ovarian cancer have been confirmed. We previously reported that ovarian cancer incidence rates at the state level were significantly correlated with the extent of pulp and paper manufacturing. We evaluated that association using county-level data and advanced geospatial methods. Specifically, we investigated the relationship of spatial patterns of ovarian cancer incidence rates with toxic emissions from pulp and paper facilities using data from the Environmental Protection Agency's Toxic Release Inventory (TRI). Geospatial analysis identified clusters of counties with high ovarian cancer incidence rates in south-central Iowa, Wisconsin, New York, Pennsylvania, Alabama, and Georgia. A bivariate local indicator of spatial autocorrelation (LISA) analysis confirmed that counties with high ovarian cancer rates were associated with counties with large numbers of pulp and paper mills. Regression analysis of state level data indicated a positive correlation between ovarian cancer and water pollutant emissions. A similar relationship was identified from the analysis of county-level data. These data support a possible role of water-borne pollutants from pulp and paper mills in the etiology of ovarian cancer.

Radon and lung cancer: What does the public really know?

Radon causes approximately 21,000 deaths annually from lung cancer, making it the second most important cause of lung cancer after smoking. However, the extent of public knowledge about radon is unclear. We systematically reviewed the epidemiologic literature in order to assay the public's understanding about radon and specifically, whether radon is known to cause lung cancer. Radon knowledge has most often been gauged via telephone and in-person responses to the question, "Have you heard about radon?" Our review of 20 such studies reveals that although many individuals have "heard about" radon, many segments of the population, particularly individuals younger than thirty and those with less education, do not know what radon is. Of those who have heard about radon, the majority of respondents in many studies did not know that radon causes lung cancer. Conversely, misinformation about radon is common; approximately 50% of respondents in many studies reported the erroneous belief that radon causes headaches. This suggests that the public has confused the effects of radon with those of carbon monoxide. Rates of radon testing and mitigation are correpondingly low and appear to reflect cognitive defense mechanisms by which individuals believe that their risks from radon are lower than the risks faced by others. Our review suggests that public information materials about radon require revision. Specifically, these should emphasize that radon causes lung cancer and that household carbon monoxide detectors do not detect it. Radon education provided by realtors at the time of residential home sales may be a promising venue to increase radon testing and remediation.

County level incidence rates of chronic lymphocytic leukemia are associated with residential radon levels.

AIM: We previously reported that incidence rates for chronic lymphocytic leukemia (CLL) among US states are significantly correlated with levels of residential radon (RR). Because these correlations could be influenced by confounding and/or misclassification among large geographic units, we reinvestigated them using smaller geographic units that better reflect exposure and disease at the individual level. METHODS: We examined the relationships between CLL and RR per county in 478 counties with publicly-available data. RESULTS: After adjustment for ultraviolet radiation, a possible risk factor for CLL, county rates for CLL and RR were significantly correlated among males and females both together and separately (p < 0.0001). CONCLUSION: CLL is significantly associated with RR at the county level.

Prediagnostic serum calcium and albumin and ovarian cancer: A nested case-control study in the Norwegian Janus Serum Bank Cohort.

BACKGROUND: Women with higher serum calcium may be more likely to be diagnosed and die of ovarian cancer. We evaluated that finding in a large, prospective cohort. METHODS: We conducted a nested case-control study using a population-based biobank from Norway. We compared 202 ovarian cancer cases and 202 controls, matched for age, date at blood draw, and county of residence, with respect to serum calcium and albumin, adjusted for anthropometric variables. We evaluated risks using the entire follow-up period as well as 2-15 years and 16-25 years ("early" and "late", respectively). RESULTS: For the entire follow-up, risk was significantly increased in the highest tertile of albumin and for high albumin and calcium jointly. Risks for ovarian cancer differed markedly by follow-up time. In early follow-up, women in the highest tertile of serum calcium had a 2.5-fold increased risk, adjusted for height and body mass index (OR=2.47, 95% C.I. 1.12-5.45) with a significant dose-response (p=0.024). Risk was not elevated in late follow-up (OR=0.62, 95% C.I. 0.27-1.36). Similarly, in early follow-up, women in the highest tertile of serum albumin had an increased risk (OR=2.55, 95% C.I.1.22-5.49) with a significant dose-response (p=0.009). Conversely, risk was not increased in late follow-up (OR=1.36, 95% C.I. 0.65-2.83). CONCLUSIONS: These data confirm a prospective association between higher serum calcium and ovarian cancer. An association in early, but not late, follow-up suggests that the higher calcium reflects the presence of existing cancer. A positive association with serum albumin is novel and should be interpreted cautiously.