Radiat Environ Biophys (2007) 46:291–296 DOI 10.1007/s00411-007-0108-1
S H O R T CO M MU N I C A T I O N
Coronary heart disease mortality and radon exposure in the Newfoundland Xuorspar miners’ cohort, 1950–2001 Paul J. Villeneuve · Rachel S. D. Lane · Howard I. Morrison
Received: 24 December 2006 / Accepted: 24 March 2007 / Published online: 24 April 2007 © Springer-Verlag 2007
Abstract 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 Xuorspar miners. Previous analyses in this cohort found elevated death rates from coronary heart disease among those with higher cumulative radon exposure. However, this Wnding was based on a relatively small number of deaths and was not statistically signiWcant. 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 Wnding 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 Wndings
P. J. Villeneuve (&) Biostatistics and Epidemiology Division, Health Canada, 269 Laurier Ave. W, 3rd Floor, 3-022 PL4903C, Ottawa, ON K1A 0K9, Canada e-mail:
[email protected] P. J. Villeneuve Department of Public Health Sciences, University of Toronto, Toronto, ON, Canada R. S. D. Lane Canadian Nuclear Safety Commission, Ottawa, ON, Canada H. I. Morrison Public Health Agency of Canada, Ottawa, ON, Canada
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.
Introduction It has been almost a decade since we reported an elevated, non-statistically signiWcant excess of coronary heart disease deaths among Newfoundland Xuorspar miners who had occupational radon exposures [1]. We advised that caution be exercised in the interpretation of these Wndings due to the relatively small numbers of coronary heart disease deaths and the inability to adjust for other risk factors for this condition. Most miner studies have not examined the relationship between exposure to radon and cardiovascular disease in great detail. Typically, studies have examined cardiovascular outcomes by comparing mortality patterns to those of the general population. Such analyses, however, are severely biased by the healthy worker eVect [2]. Analysis of Japanese atomic bomb survivors with a single acute exposure below 4 Sv found increased noncancer mortality rates for exposures at around 0.75 Sv. This association was determined to be approximately linear, and it was estimated that each additional Sv of radiation increased heart disease mortality by 0.17 (90% CI = 0.01 ¡ 0.26) [3]. Occupational studies have also found positive associations between those exposed to radiation and cardiovascular mortality [4, 5]. However, a systematic review of the literature by McGale and Darby [6] concluded that the epidemiologic data examined to date are subject to important biases and limitations, and that it remains unclear whether doses of ionizing radiation under 4 Sv increase the risk of circulatory disease.
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Recently, Kreuzer et al. [7] found no association between exposure to radiation and death from cardiovascular disease among German uranium miners. We have recently reported on the association between radon exposure and lung cancer in an extended follow-up of the Newfoundland Xuorspar cohort [8]. It is the analyses of Kreuzer and colleagues that motivated us to also report our Wndings for coronary heart disease (CHD) mortality. Since the last time CHD mortality was examined, the follow-up of Xuorspar cohort has been extended by a decade, which has provided increased statistical power [1]. A positive feature of the Xuorspar cohort is that, unlike uranium miners, the only source of radiation was from radon found in the ground water running through the mine. Therefore, eVects of gamma radiation, thoron and radioactive dust can be ruled out.
Radiat Environ Biophys (2007) 46:291–296
2001). The utility of using this database to ascertain vital status and underlying cause of death has been demonstrated [12, 13]. The coding of the underlying cause of death in the CMDB is fairly complete, and in this cohort, all mortality links from 1950 onwards contained this information. Deaths from coronary heart disease were determined using the underlying cause of death based on ICD-9 codes 410– 414, and 429.2. Deaths from circulatory diseases (ICD-9; 390–459), acute myocardial infarction (ICD-9; 410), and cerebrovascular diseases (ICD-9; 430–438) were also examined. As mentioned previously, the quality and completeness of death registrations before 1950 precluded their use. For those records available before 1950, the CMDB does not capture the underlying cause of death electronically. Our analyses are based on the follow-up period between 1950 and 2001. Assignment of radon exposures
Methods Study population The history of mining operations and the development of a cohort of miners who worked in the St Lawrence region of Newfoundland has been described in great detail elsewhere [9–11]. BrieXy, the cohort consisted of approximately two thousand workers employed at one of two companies between 1933 and 1978. Occupational histories were constructed from administrative records. Miners who lacked suYcient personal identifying information, mainly those employed short-term during World War II, were dropped from analyses. Miners who died before 1950 were excluded, as well as an additional 19 workers who were born before 1900 and for whom no death certiWcate could be found. While this exclusion would have had a negligible impact on the presented risk estimates and their standard errors, these individuals most likely died before 1950 when death registration for Newfoundland in the Canadian Mortality Data Base was incomplete. Newfoundland joined Canada as the tenth province on 31 March 1949. These analyses are based on 1,742 individuals who worked underground at some point during their employment at the mine, and 328 mill workers who worked exclusively on the surface.
Corkill and Dory [14] carried out a retrospective study for the assignment of exposures for epidemiological studies. Exposures were assigned on an individual basis after taking into account the mine worked in, the calendar year, and job duties. There was no monitoring of radon levels until 1960, and the assignment of exposures before this time was based on a variety of sources that included mine architecture, reports by inspectors, Commission hearings, workers’ recollection, as well as 80 radon-progeny samples taken in 1960 before the introduction of mechanical ventilation. Some attempt was also made to take into account changes in the entry of water, the source of radon, into the mines. Radon levels in 1960 were highly variable and ranged from 0.4 to 193 WL in unventilated areas, and from below the level of detection to 12 WL in ventilated areas of the mines. In 1960, mechanical ventilation was introduced at 50 diVerent underground locations in the principal mine then in operation. Between 1961 and 1967, the average radon exposures were less than 0.3 WL, and of the 700 samples taken annually, only about 3% of readings were in excess of 1 WL. Daily radon exposures for each worker were estimated based on levels measured in the place worked in a given day from 1968 to 1978. Over this period, the mean exposure was 0.17 WL. Cigarette smoking
Ascertainment of vital status As with previous analyses of this cohort, the vital status of the cohort members was determined by linking personal identifying information from occupational Wles to the Canadian Mortality Data Base (CMDB). Given the completeness of the CMDB, when no links were found, miners were assumed to be alive at the end of follow-up (31 December
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Smoking surveys were administered to miners in 1966, 1970, 1978, 1993 and 2003. These individuals were identiWed using personal identifying information obtained from the occupational Wles. These data allowed individuals to be categorized according to their lifetime smoking status, and number of cigarettes smoked daily. Data collected from the surveys allowed us to classify approximately 54% of the
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cohort according to their smoking status. For individuals who participated in more than one survey, smoking status was determined based on responses from the earliest survey. This was done as it was felt that the responses to the earlier survey would be more likely to be free of recall bias, and false statements due to sensitivity related to any possible compensation claims. Statistical methods An internal cohort analysis was used to estimate the risk of death from coronary heart disease in relation to cumulative exposure to radon. The method of indirect standardization to compare the mortality experience of the cohort to the general population was not used, as this comparison would be biased by the healthy worker eVect, particularly for coronary heart disease. However, for interested readers, standardized mortality analyses for several causes of death using the updated follow-up of the cohort are presented elsewhere [8]. For each miner, the cumulative exposure to radon and the number of person-years of follow-up was calculated from the date of Wrst employment until the earliest of date of death, or 31 December 2001. Consistent with previous analyses of this cohort [1, 8], and elsewhere [7], cumulative WLM exposures were lagged by 5 years. As mentioned previously, deaths that occurred before 1950 were excluded, and therefore, our risk estimates are based only on person-years accrued from 1950 onwards. Data were cross-classiWed by age-group (1,600
2,476.36
2,942
17
1.19
0.70–2.03
1.18
0.67–2.08
Linear test for trend
P = 0.54
P = 0.63
a
Reference category WLM = Working level months. A lag interval of 5 years was incorporated into the calculation of cumulative exposure and person-years of follow-up c The mean WLM was calculated across the person-years within the cumulative exposure category d Relative risks were adjusted for age, and calendar period e Relative risks were adjusted for age, calendar period, and lifetime cigarette smoking status (never, ever, unknown) b
Table 4 The relative risk (RR) of circulatory disease, cerebrovascular, and acute myocardial infarction mortality in relation to cumulative exposure to radon progeny (in WLM), Newfoundland Xuorspar cohort, 1950–2001 Cumulative exposure to radon (in WLM)
Person-years
All circulatory deaths (ICD-9; 390–459) Deaths
RRb
95% CI
1.0a
Acute myocardial infarction (ICD-9; 410) Deaths
RRb
40
1.0a
95% CI
Cerebrovascular disease (ICD-9; 430–438) Deaths
RRb
20
1.0a
95% CI
0
17,056
99
>0–100
32,421
124
0.99
0.75–1.31
54
1.00
0.65–1.53
13
0.63
0.30–1.32
>100–400
10,538
80
1.20
0.88–1.62
38
1.30
0.82–2.06
9
0.73
0.32–1.66
>400–800
4,707
41
1.47
1.01–2.16
21
1.68
0.96–2.92
6
>800–1,600
3,230
21
1.10
0.68–1.80
10
1.15
0.56–2.37
0.49
0.18–1.34
>1,600
2,942
24
1.18
0.74–1.89
13
1.39
0.71–2.69
Linear test for trend a b
P = 0.40
P = 0.31
p = 0.55
Reference category The relative risk was adjusted for age, calendar period, and lifetime cigarette smoking status (never, ever, unknown)
The interpretation of Wndings for coronary heart disease mortality, as aptly pointed out by Kreuzer et al. [7], is made diYcult as there are a large number of risk factors for this health condition. These include, among others, high blood pressure, cigarette smoking, hypercholesterolaemia and diabetes. Other lifestyle factors such as diet, alcohol use, stress and smoking, physical activity and other occupational agents have also been shown to play a role. While our Wndings suggest that high occupational radon levels are unrelated to death from coronary heart disease, our risk estimates may be biased by our inability to control for some of these other risk factors. The standardized mortality ratios (SMR) for coronary heart disease over the period between 1950 and 2001 among those who worked underground in the Xuorspar mines was 0.86 (95% CI = 0.74 ¡ 0.89) [8]. The seemingly reduced death rate for coronary heart disease in this group is a reXection of the health worker eVect [2]. Discrepant
Wndings between the internal cohort analyses presented in this short communication and the reduced SMR underscore the need to conduct within cohort comparisons when exposure data are available. The radon exposure levels in this cohort were quite high, as approximately one quarter of the miners had average annual exposures that exceed 60 WLM/year, or a cumulative exposure in excess of 250 WLM. The mean cumulative exposure in the Xuorspar cohort was slightly higher (348 WLM) than that observed among German uranium miners (241 WLM) [7]. Comparisons of exposure levels between these two cohorts and the atomic bomb survivors are not straightforward as exposures among miners were received over a longer time interval. Perhaps more importantly, comparisons are made diYcult because miners were exposed to radon progeny, which is alpha radiation and not the gamma radiation received by the a-bomb survivors and radiotherapy patients. Gamma radiation can directly penetrate
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the skin. The miners breathed the radon gas into their lungs then the decay products which have very short half-lives, gave oV their radioactive energy in the lungs thus damaging sensitives lungs tissue. In contrast, dosimetry estimates for inhaled radon progeny indicated that doses to the blood however, dosimetry estimates for inhaled radon progeny indicate that doses to the blood and arteries are less than 1% of that received by the lung [18]. It is commonly assumed that 1 WLM is equal to a lung dose of 5 mSv [19]. As a result, the dose delivered to the heart may be too small to detect eVects relative to other study populations, such as the atomic bomb survivors, where cardiovascular eVects have been noted. In summary, the data presented indicate that cumulative exposure to radon progeny does not increase the risk of death from coronary heart disease, circulatory diseases, cerebrovascular disease, or acute myocardial infarction. These Wndings should be interpreted in light of the limitations of this study design. Acknowledgments We thank the Occupational and Environmental Health Division at Statistics Canada, in particular Lana Marjama and Dores Zuccarini, for their assistance in linking the Newfoundland Xuorspar cohort to the Canadian Mortality Data Base. The Canadian Nuclear Safety Commission provided funding support for this project.
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