Updated Analysis of Radon Exposure and Lung Cancer Mortality in the Cohort of Newfoundland Fluorspar Miners (1950-2016).

The commercial mining of fluorspar in St. Lawrence Newfoundland began in 1933. Miners who worked underground were exposed to high levels of radon progeny, especially before ventilation was introduced into the mines in 1960. The mean cumulative radon exposure for underground miners in this cohort was 380.9 working level months (WLM). A series of studies of this cohort have characterized the increased risks of lung cancer mortality due to radon. We have extended the follow-up of this cohort an additional 15 years to provide additional insights on the risks of low levels of radon exposure, and the modifying effects of time since exposure, age at first exposure, attained age, duration of exposure, and cigarette smoking. The cohort consisted of 1,735 underground and 315 male surface miners who, combined, accrued 81,650 person-years of follow-up. The mortality experience of the cohort was determined from 1950-2016 through record linkage to Canadian national death data. Individual-level estimates of exposure to radon progeny, in WLMs, were determined for each year of employment. We compared the mortality experience of the underground miners to Newfoundland men using the standardized mortality ratio (SMR). Poisson regression models were fit to estimate excess relative risks (ERR) per 100 WLM. There were 236 lung cancer deaths identified, and of these, 221 occurred among underground workers. The SMR for lung cancer among underground miners compared to Newfoundland men was 2.67 (95% CI: 2.33, 3.04). The ERR per 100 WLM for lung cancer mortality, assuming a 5-year exposure lag, was 0.41 (95% CI: 0.23, 0.59). Attained age and time since exposure were important modifiers to the radon-lung cancer relationship. The joint relationship between smoking and radon on lung cancer risk was sub-additive, however, the smoking data were limited and available for only half of the cohort.

Circulatory system disease mortality and occupational exposure to radon progeny in the cohort of Newfoundland Fluorspar Miners between 1950 and 2016.

OBJECTIVES: Exposure to ionizing radiation may increase the risk of circulatory diseases, including heart disease. A limited number of cohort studies of underground miners have investigated these associations. We previously reported a positive but non-statistically significant association between radon progeny and heart disease in a cohort of Newfoundland fluorspar miners. In this study, we report updated findings that incorporate 15 additional years of follow-up. METHODS: The cohort included 2050 miners who worked in the fluorspar mines from 1933 to 1978. Statistics Canada linked the personal identifying data of the miners to Canadian mortality data to identify deaths from 1950 to 2016. We used previously derived individual-level estimates of annual radon progeny exposure in working-level months. Cumulative exposure was categorized into quantiles. We estimated relative risks and their 95% confidence intervals using Poisson regression for deaths from circulatory, ischemic heart disease and acute myocardial infarction. Relative risks were adjusted for attained age, calendar year, and the average number of cigarettes smoked daily. RESULTS: Relative to the Newfoundland male population, the standardized mortality ratio for circulatory disease in this cohort was 0.82 (95% CI 0.74-0.91). Those in the highest quantile of cumulative radon progeny exposure had a relative risk of circulatory disease mortality of 1.03 (95% CI 0.76-1.40) compared to those in the lowest quantile. The corresponding estimates for ischemic disease and acute myocardial infarction were 0.99 (95% CI 0.66-1.48), and 1.39 (95% CI 0.84-2.30), respectively. CONCLUSIONS: Our findings do not support the hypothesis that occupational exposure to radon progeny increases the risk of circulatory disease.

Determinants of delays in treatment initiation in children and adolescents diagnosed with leukemia or lymphoma in Canada.

Minimizing delays that may occur along the cancer care pathway requires an understanding of their determinants. Few studies on childhood cancers have been published on the factors that influence the time it takes for patients to get a first medical consultation (patient delay) and treatment (health care system [HCS] delay) once cancer symptoms have been recognized. Our objective was to assess factors related to disease, patient and HCS on patient and HCS delay for children and adolescents with leukemias and lymphomas in Canada. A prospective cohort study was conducted on subjects enrolled in the Treatment and Outcomes Surveillance program of the Canadian Childhood Cancer Surveillance and Control Program, a national surveillance program. We studied 963 leukemia and 397 lymphoma patients who were less than 19-years old at diagnosis in 1995-2000. Logistic regression models were used to measure the associations between candidate predictive factors and delays. Age was positively associated with patient delay for both leukemia and lymphoma patients, but not with HCS delay. Patients first seen in a hospital emergency room had a lower risk of HCS delay than patients first seen by a general practitioner. Cancer subtype was associated with patient delay for leukemia patients, and HCS delay for lymphoma patients. Longer patient delay was associated with a lower risk of long HCS delay for both cancers. Factors related to the patients, their disease and the HCS may exert different influences on varying segments of the care pathway of leukemia and lymphoma patients.

Delays in diagnosis and treatment among children and adolescents with cancer in Canada.

BACKGROUND: Few studies have investigated delays in diagnosis and treatment among children and adolescents with cancer, especially from the perspective of an entire country. Detailed understanding of delays along the continuum of cancer patient care is important in order to establish appropriate benchmarks for timely oncological care. Our objective was to characterise the different components of delay in 2,896 Canadian children and adolescents (aged 0-19 years) with cancer that were enrolled in the Treatment and Outcome Surveillance component of the Canadian Childhood Cancer Surveillance and Control Program from 1995 to 2000. PROCEDURE: We examined median and standardised means concerning the distribution of delay times across categories of pertinent variables and over time. The word "delay" was used simply to represent a time interval, measured in days, without implying whether this interval exceeded a particular threshold of clinical acceptability. RESULTS: The median times (and inter-quartile ranges) for patient, diagnosis and healthcare system delays for all cancers were 9 (1-31), 30 (13-69) and 12 (4-35) days, respectively. The median total delay was 34 (16-76) days. CONCLUSIONS: Patient and referral delays were the longest time segments influencing timely diagnosis. Differences in delays were observed across age groups, cancer types and geographical regions. There was a significant trend for decreasing delays to diagnosis and treatment.

Coronary heart disease mortality and radon exposure in the Newfoundland fluorspar miners' cohort, 1950-2001.

Kreuzer and coworkers recently reported no association between cumulative exposure to radiation and death from cardiovascular disease in a cohort of German uranium miners. Here, we report on the relationship between cumulative exposure to radon progeny and coronary heart disease among Newfoundland fluorspar miners. Previous analyses in this cohort found elevated death rates from coronary heart disease among those with higher cumulative radon exposure. However, this finding was based on a relatively small number of deaths and was not statistically significant. Since then, the follow-up of this cohort has been extended by 10 years until the end of 2001. Among the 2,070 miners in our study, 267 died from coronary heart disease. There was no trend evident between cumulative exposure to radon and the relative risk of death from coronary heart disease (P = 0.63). This finding was unchanged after adjusting for the lifetime smoking status that was available for approximately 54% of the cohort. Similarly, the cumulative radon exposure was found to be unrelated to deaths of the circulatory system, acute myocardial infarction, and cerebrovascular disease. These findings are consistent with those recently reported by Kreuzer and colleagues. We share their view that uncontrolled confounding for other coronary heart disease risk factors hinders the interpretation of the risk estimates.

Radon and lung cancer risk: an extension of the mortality follow-up of the Newfoundland fluorspar cohort.

Radon is a well-recognized cause of lung cancer, and studies of underground miners have provided invaluable insights on the mechanisms of radon carcinogenesis. Given the dramatic decreases in occupational exposures and the latent interval between the time of exposure and the development of lung cancer, continued follow-up of these cohorts is needed to address uncertainties in risk estimates. Here, we report on the relationship between radon and lung cancer mortality in a cohort of 1,742 Newfoundland fluorspar miners between 1950 and 2001; follow-up has been extended 11 y from previous analyses. The standardized mortality ratio (SMR) was used to compare the mortality experience of the cohort to similarly aged Newfoundland males. Poisson regression methods were used to characterize the radon-lung cancer relationship with respect to: age at first exposure, attained age, time since last exposure, interactions with cigarette smoking, and exposure rate. In total, 191 lung cancers were observed among underground miners (SMR = 3.09; 95% CI = 2.66, 3.56). ERR/WLMs decreased with attained age and time since last exposure. An inverse dose-rate effect was observed, while age at first exposure was not associated with lung cancer risk. An important strength of this study is that the effects of gamma radiation, thoron, and radioactive dust, common exposures in other miner studies, can be ruled out because the source of radon was from water running through the mine. However, the results should be interpreted cautiously due to uncertainties associated with the estimation of radon exposure levels before ventilation was introduced into the mine, and the relatively small number of lung cancer deaths that precluded joint modeling of multiple risk factors.

Health-related quality of life among child and adolescent survivors of childhood cancer.

PURPOSE: The main objective was to compare parent-reported health-related quality of life (HRQL) of child and adolescent survivors of childhood cancer to that of controls who had no history of cancer. METHODS: We assessed HRQL of 800 child and adolescent survivors younger than 16 years and 923 randomly selected, age- and sex-matched controls from the general population in a national multicenter retrospective cohort study using the Child Health Questionnaire parent report. Participation was 69% among survivors and 57% among controls. RESULTS: Survivors had means that were consistently lower than controls on the HRQL physical summary (PH; 49.9 v 55.3; P <.005), psychosocial summary (PS; 49.4 v 52.6; P < .005), and all but one of the eight subscale scores. Clinically important survivor-control differences in means on PH were found for survivors of CNS tumors, bone tumors, lymphoma, leukemia, soft tissue sarcoma and Wilms' tumor (differences: -8.7, -7.0, -6.3, -5.4, -4.4, -3.8/100, respectively); on PS, survivors of CNS tumors were most compromised (-6.1/100). Survivor-control differences in both PH and PS were also large for survivors treated with radiation only (-5.8 and -11.9/100, respectively), or radiation combined with surgery (-6.6 and -5.9/100, respectively), or radiation combined with both surgery and chemotherapy (-7.8 and -5.1/100, respectively). Cranial radiation was associated with the most compromised HRQL. CONCLUSION: According to parents, HRQL for survivors was somewhat poorer, overall, than for controls. Survivors of CNS tumors, lymphoma, and leukemia and those patients treated with cranial radiation were reported to have poorest HRQL. These findings support development of guidelines for levels of follow-up care for particular groups of survivors.

Use of medication during pregnancy and risk of childhood leukemia (Canada).

OBJECTIVE: To examine risk of childhood acute lymphoblastic leukemia (ALL) associated with maternal use of medications during pregnancy; in particular medications known or suspected to be teratogenic. METHODS: Seven hundred and eighty nine children (< 15 years old) diagnosed with ALL in the province of Quebec between 1980 and 2000 were recruited for study. A similar number of population based controls matched to cases (1:1) by sex and age were chosen from family allowance or health insurance files. Information was gathered via telephone interview with the subjects' parents. Data were analyzed using conditional logistic regression. RESULTS: Risk of childhood ALL was significantly increased in the offspring of mothers who reported using any medication (adjusted odds ratio (OR(adj)) = 1.3, 95% CI = 1.0-1.6) or any teratogenic medication (OR(adj) = 1.4, 95% CI = 1.1-1.9) during pregnancy. Among specific medication categories, only central nervous system depressants were associated with a significantly increased risk, although elevated odd ratios were found for anti-epileptics, immunosuppressants, oral contraceptives, and illicit drugs. Risk associated with use of teratogenic medications was higher with increased dose and in children diagnosed before two years of age. CONCLUSION: A modest increase in risk of ALL was found among children of mothers who used medication during pregnancy.

The late effects study: design and subject representativeness of a Canadian, multi-centre study of late effects of childhood cancer.

The Late Effects Study of the Canadian Childhood Cancer Surveillance and Control Program was designed to assess psychosocial and physical health outcomes among survivors of childhood cancer compared to general population controls. The objectives of this paper are to describe the design and methodology of the multi-centre, retrospective cohort study, present clinical characteristics of the survivor population, and evaluate the representativeness of study controls. Response rates were 63% for surivors (n = 2,152) and 49% for controls (n = 2,432). Survivors with germ cell turmours and carcinomas were slightly under-represented among participants as were those who received more intense or multiple series of therapy. Study controls were similar to Census individuals based on marital and work status but did have a slightly higher level of education and income. Otherwise, no large or systematic differences were found. Thus, these long-term survivors and population controls can be validly studied to evaluate whether and to what extent survivors experience an excess of psychosocial or physical health problems compared to similarly aged Canadians who have never had cancer.

Environmental tobacco smoke and deaths from coronary heart disease in Canada.

A series of recent meta-analyses have concluded that non-smokers who live with smokers face an elevated risk of coronary heart disease (CHD). In this study, we estimated the number of CHD deaths among non-smokers attributable to environmental tobacco smoke (ETS) exposure in their homes. Population-attributable risk estimates suggest that in 1997 over 800 Canadians died of CHD caused by passive exposure to ETS. This figure is likely an underestimation of the total number of CHD deaths attributable to ETS, since our study did not estimate the number of deaths among non-smokers caused by ETS exposure in the workplace. However, this partial picture can still help to highlight the burden of disease resulting from this pervasive involuntary environmental exposure.