Answer to Question #1254 Submitted to "Ask the Experts"

Q

A very rigorous study appeared in Science, 1980. (People’s Republic of China High Background Radiation Research Group, 1980, Health survey in high background radiation areas in China: Science, v. 209, pp. 877-880). It convincingly showed that long-term effects of elevated background radiation (at common low levels) do not lead to increased health problems. Two groups of 70,000 each were selected in rural Guangdong Province. One of these groups lived in valley terrain, and their background radiation was about 100 mrem/yr (about equivalent to 2 to 4 pCi/L). The other group lived on a plateau where the rocks brought background radiation to 250-300 mrem/yr (about equivalent to 5 to 12 pCi/L). These individuals were not transient, and they could easily trace their ancestry back at least four or five generations. The two separate groups wore dosimeters for five years (1974-1979), after which time the devices were collected and measured. The results were studied for two years. The health effects—short term and long term—between the two groups were identical within the limits of the uncertainties involved. The data base for this single study contains none of the meta-analyses problems associated with combined data and is more than double the total data base obtained by combining the data of all individual studies of miners. Further, it confirms from the field what Miller predicted would be found in 1999 (Miller, R. C., and others, 1999, “The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei”: Proc. National Academy of Sciences, v. 96, pp. 19-22.) My question is, was the Chinese study bunk? It seems like a critical paper to cite, but it is never cited by the U.S. Environmental Protection Agency, etc., on discussions of radon. I cite it often in my classes, but I worry that for some reason this paper was found flawed and I don't know about the flaw—same with Miller's paper.

A

Cancer and other health conditions have been investigated in areas in southern China (near Yangjiang in Guangdong province) with especially high levels of natural background radiation for nearly 30 years (Wei 1980; Wei 2000). The increased radiation levels arise in part from monazite sands which contain thorium and are washed down year after year from nearby mountains. Natural radioactive nuclides in building materials is the primary source of population exposure. About 80,000 residents have lived in these areas for more than two generations. The annual effective dose is estimated to be 6.4 mSv (640 mrem) which is about three times the world’s average of 2.4 mSv (240 mrem) and three times that of the nearby control areas in Enping county (Wei 2000; UNSCEAR 2000). Cytogenic studies of blood lymphocytes have indicated higher levels of chromosomal aberrations among persons living in the high background areas, confirming the physical dosimetry of a difference in population exposure (Wang 1990; Wei 2000). Recent mortality analyses have been conducted in collaboration with Japanese scientists and include deaths from 1979 to 1995 (Table below) (Wei 2000). Practically all studies have failed to reveal any significant health effects that could be attributed to living in these areas of high natural background radiation.

Table. Effective doses for single x-ray films

*All values taken from Wei (2000) except radon WLM which were from Hofmann (1986). Slight differences in numbers occur in the various articles found in Wei (2000).

**Relative risk of death among persons living in the high-background-radiation areas compared to persons living in the control areas.

 

The China High Background Radiation Study is well designed, carefully conducted, and carefully analyzed (Wei 2000). It is an ecologic study since radiation doses to individuals are not known but have to be estimated indirectly from environmental samples and applied to groups living in hamlets with assumed occupancy factors. Variations in dose depended on village location, type of dwelling, ventilation, occupancy and other factors.

In general, such ecologic studies are not considered as informative as epidemiologic case-control studies (such as of indoor radon) or cohort studies (such as of underground miners) where attempts are made to estimate doses to individuals and to obtain risk factor information (such as cigarette smoking) at the individual level. The study results have been considered in both the recent National Academy of Sciences BEIR VI report (NAS 1999) and the United Nations’ UNSCEAR report (UNSCEAR 2000). The doses in the China high background areas (6.4 mSv y^-1), however, appear too small and the dose distribution too narrow to provide convincing evidence on the presence or absence of radiation effects.

At such low doses, even 80,000 subjects can be considered insufficient to detect an excess risk, given that one existed, that is, the study has low statistical power. For example, a typical individual in the high background area might by age 50 years have received a dose that was about 200 mSv (20,000 mrem) greater than someone living in the lower dose control areas. Based on estimates from the study of atomic bomb survivors (ERR=1.0 Sv^-1), acute doses of this magnitude might be expected to result in a relative risk (RR) of lung cancer of the order of 1.20 (UNSCEAR 2000). Relative risks of this magnitude are difficult, if not impossible, to detect epidemiologically, so even if the observations of persons living in these areas are extended over a lifetime it will be difficult to obtain a definitive result.

This exemplifies the difficulties in directly studying the possible effects of low doses of radiation. Even if you don’t find an increased risk, your study may not be powerful enough to reject the possibility of a low risk predicted from higher dose studies. The authors acknowledge the limitations of their study that are related to the small number of cancer cases and the relatively low doses experienced, especially for site-specific analyses (Wei 2000). For example, during the years 1979-95 the total number of lung cancer deaths in the high background and control areas were only 62 and 32, respectively. In comparison, the studies of indoor radon and of underground miners include many thousands of lung cancer cases. The risk of lung cancer was lower in the high background area compared to the control area (RR=0.81; 95% = 0.53-1.24) but not significantly so.

A more sophisticated analysis (Wei 2000) estimated the ERR per Sv for lung cancer to be -0.68 (95% CI = -1.58 to 1.66), again not statistically significant and thus consistent with a protective effect (the negative value), no difference (the 95% CI includes 0.00), and an effect greater than seen among atomic bomb survivors (1.66 is greater than the A-bomb ERR per Sv estimate of 1.00). In other words, the play of chance (random variation) is still too great for the China study to provide convincing results. Nonetheless, this study does make a useful contribution to our understanding of radiation-induced cancers because it can provide an upper limit to the possible risk.

Although a small risk cannot be excluded, radiation risks are unlikely to be much larger than currently assumed for the purposes of radiation protection. While the strengths of this study include the relatively large population, the careful environmental dosimetry program, a comparison population, low migration, and genetic homogeneity, there are limitations. The weaknesses include the uncertainties in dose estimates actually received by individuals, the low and narrow range of cumulative doses, and the possibility that important demographic and lifestyle factors might differ between the high background and control populations.

While attempts to evaluate potential confounding factors revealed no significant differences, there were indications that the control population had slightly higher rates of cigarette smoking, slightly higher access to medical care, and slightly higher rates of viral infections. These factors would result in slightly higher rates of reported cancers in the control population (which were seen) and, accordingly, slightly lower relative risks in the exposed population. The relative risk of lung cancer due to cigarette smoking in China is 5 to 10 and a small difference in smoking prevalence could easily overshadow a possible relative risk of 1.2 due to radiation.

Better access to medical care could mean slightly better and more frequent diagnoses of lung cancer; for example, a lung neoplasm would be less likely to be mistaken for tuberculosis or other prevalent lung disease. It is of interest that 45% of all cancer deaths were due to liver cancer and nasopharyngeal cancer, and both of these cancers have strong viral etiologies. If these cancers are excluded from the overall analyses of total cancers, the ERR per Sv goes from a nonsignificant negative (-0.11; 95% CI = -0.67 to 0.69) to a nonsignificant positive (0.24; 95% CI = -0.53 to 1.49) value. For comparison, the ERR per Sv for A-bomb survivors (1950-1990) is 0.53 (95% CI = 0.43 to 0.64), a value statistically consistent with either of these estimates from the China background study.

Again, these examples point to the fragile nature of the radiation risk estimates derived from the China study and point to caution in interpretation. Analyses restricted solely to low doses are thus complicated by the limitations of statistical precision, the potential for misleading findings owing to any small, undetected biases, and any confounding influences such as smoking tobacco which are not accounted for. Slight biases and confounding influences take on much more importance when the signal to detect is so low compared to the background noise. When the RR gets below 1.3 or 1.4 the uncertainties in the data become so great that results can be suspect.

The inability to detect increases at very low doses using epidemiological methods does not mean that the underlying cancer risks are not elevated, but rather that epidemiology alone will not be able to resolve the issue of whether there are dose thresholds in risk (UNSCEAR 2000). The Miller et al (1999) cell transformation study is interesting and potentially important. They found that the oncogenic potential of a single alpha particle, with an energy similar to that of radon decay progeny, was significantly less than that from a Poisson distributed mean of one alpha particle. This finding suggests a nonlinear response at low doses of high-LET, that is, that the risk of radon-induced cancers would be lower than predicted based on high-dose extrapolation. These results, however, have not been replicated, and their applicability to human exposure and low-dose risk assessment is yet to be determined.

Other than the forthcoming meta-analyses of indoor radon studies, is there any new information on the horizon concerning radon and lung cancer? There is one interesting study, soon to be published, on the risk of lung cancer among persons in China who lived in underground dwellings for most of their lives. The radon levels were especially high, cumulative exposure levels were estimated for individuals, and information on smoking histories and other factors potentially associated with lung cancer risk were obtained (Wang 1996; Lubin in press). So stay tuned.

References

• Hofmann W, Katz R, Zhang CX. Lung cancer risk at low doses of alpha particles. Health Phys 51:457-68; 1986.
   
• Lubin JH, Wang ZY, Kleinerman RA, Boice JD Jr, Metayer C, Cui H, Brenner A, Conrath S, Chen K, Wang Long De. Residential radon and lung cancer in a high exposure area with underground dwellings in Gansu Province, China. Am J Epidemiol (In Press).
   
• Miller RC, Randers-Pehrson G, Geard CR, Hall EJ, Brenner DJ. The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei. Proc Natl Acad Sci USA. 96:19-22; 1999.
   
• National Academy of Sciences. Committee on Health Risks of Exposure to Radon. (BEIR VI). Washington, DC: National Academy Press; 1998.
   
• UNSCEAR: United National Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000 Report to General Assembly, with Scientific Annexes, Sources and Effects of Ionizing Radiation. New York: United Nations; 2000.
   
• Wang Z-Y, Lubin JH, Wang LD, Conrath S, Zhang SZ, Kleinerman R, Gao SX, Gao PY, Lei SW, Boice JD Jr. Radon measurements in underground dwellings from two prefectures in China. Health Phys 70:192-198; 1996.
   
• Wang Z, Boice JD Jr, Wei L, Beebe GW, Zha Y, Kaplan MM, Tao Z, Maxon HR III, Zhang S, Schneider AB, Tan B, Wesseler TA, Chen D, Ershow AG, Kleinerman RA, Littlefield LG, Preston D. Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China. J Natl Cancer Inst 82:478-485; 1990.
   
• Wei L. Health survey in high background radiation areas in China. Science 209:877-880; 1980.
   
• Wei LX, Sugahara T, eds. High background radiation area in China. J Radiat Res 41 (Suppl):1-76; 2000.
  
  
  

 John D. Boice, Jr., ScD