Incidence of non-lung solid cancers in Czech uranium miners: A case–cohort study

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Abstract

Objectives: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic.

Methods: A retrospective stratified case–cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996.

Results: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73–1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69–1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52–10.98, n=13), 0.79 for larynx cancer (95% CI 0.38–1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91–9.42, n=23), 0.84 for bladder cancer (95% CI 0.43–1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62–2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon.

Conclusions: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out.

Research highlights

► Uranium miners are chronically exposed to radon. ► We evaluate risk of non-lung solid cancers among uranium miners. ► No cancer type was significantly associated with radon exposure. ► Malignant melanoma and gallbladder cancer showed non-significant elevated risk.

Introduction

Uranium miners are chronically exposed to many external risk factors, most prominent among them being ionizing radiation whose carcinogenic effect is generally known. The first type of cancer that was found to be associated with ionizing radiation in uranium miners was bronchogenic lung cancer (Saccomanno et al., 1964, Řeřicha and Šnajberk, 1966). Consequently, lung cancer has been long acknowledged as an occupational disease in uranium miners (BEIR VI, 1999). A recent study (Řeřicha et al., 2006) reported a significant association of radon exposure with leukemia, especially chronic lymphocytic leukemia, a leukemia type that has been previously considered non-radiogenic.

Several studies have investigated mortality from other types of cancer in uranium miners and other workers exposed to radon (Tomášek et al., 1993, Darby et al., 1995, Vacquier et al., 2008, Tirmarche et al., 1993, Laurier et al., 2004, Checkoway et al., 1988, Kreuzer et al., 2008, Kreuzer et al., 2010). Some of them found increased mortality from various cancers of the digestive tract (Tomášek et al., 1993, Darby et al., 1995, Kreuzer et al., 2008) or renal and urinary tract cancers (Tomášek et al., 1993, Vacquier et al., 2008). One study reported excess mortality from larynx cancer (Tirmarche et al., 1993). A large German study (Kreuzer et al., 2010) has recently identified a positive association between radon and mortality from cancer of extrathoracic airways and trachea.

Nearly all reported positive findings were all based on standardized mortality ratios (SMR) comparing cancer mortality in the miners to that in the general population, with no clear association between radon exposure and mortality among the miners themselves. All previous miner studies share several of the following important design limitations: they investigated mortality instead of incidence and could have missed a number of cases, especially of less aggressive cancers; they included small number of cases because of insufficient cohort size or follow-up duration; the primary analysis made use of comparisons with the general population (SMR) rather than of trends with exposure to radon; and, last but not least, they did not account for smoking, an important risk factor for many of the cancers of interest (Kuper et al., 2002). Thus, despite the lack of consistent positive associations between working exposure and non-lung cancer mortality, it is yet unclear whether underground work in uranium mines, and in particular exposure to prolonged low levels of radon, can cause solid cancers other than lung cancer.

This paper reports the results of a case–cohort incidence study conducted in uranium miners working in Příbram region in the Czech Republic to evaluate and test associations of radon exposure with the incidence of various types of cancer. The study differs from the previous studies in that it investigated incidence rather than mortality and included a substantially larger number of cases. The case–cohort design allowed more detailed evaluation of work-related exposures and assessment of smoking status. Lymphoma, myeloma, and leukemia results from the case–cohort study were published earlier (Řeřicha et al., 2006). This report focuses on the incidence of non-lung solid cancers.

Section snippets

Location and study population

Most of the uranium produced in the former Czechoslovakia was mined near the town of Příbram. Uranium mines operated in that area from 1949 till 1991 and over that time employed a total of almost 50 thousand people. The employer, Uranium Industry, maintained a registry of all workers as well as special employment logs for those who were at risk for radiation exposures. The Uranium Industry registry was used to define a population for this study. First, we identified all 27,441 male workers who

Results

A total of 1020 cases of incident cancer at the sites of interest were identified among eligible miners who worked underground for 12 months or more. The most frequent diagnosis was rectal cancer (145 cases), followed by stomach cancer (138 cases), and colon cancer (109 cases). Other relatively common sites included bladder, kidney, prostate, mouth, larynx, and pancreas. Basic characteristics of the study population are summarized in Table 1. For comparison, the table also presents estimated

Discussion

The present study does not indicate unequivocally that uranium miners are at increased risk for non-lung solid cancers. The results do not rule out a positive association of radon with incidence of malignant melanoma and/or gallbladder cancer, but these cancer types are too rare to be evaluated with sufficient precision even in a study of this size. A link between radon and malignant melanoma is biologically plausible, though no previous human or animal studies have demonstrated an increased

Acknowledgments

We are greatly indebted to the Regional Hospital in Příbram (Czech Republic) and the Uranium Industry Concern for the long-term support of this project, providing exposure data and mediating access to government agencies.

This study was financed by research contracts and additional support from the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-049029) and by the Regional Hospital in Příbram.

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