云锡矿工肺癌病因学研究的概况

本文简要回顾了近３０年来云锡矿工肺癌病因学研究的概况，介绍了“氡砷复合，以氡为主”的病因学观点的现场研究与实验室研究的证据，提出矿工肺癌病因中氡／砷相对贡献的比值，提出利用该比值制定氡砷复合暴露时井下氡－砷空气浓度限值的办法及供肺癌矿工职业赔偿使用的计算病因概率的参数。作者认为由于存在一些技术上的问题，目前很难根据现有的流行病学研究资料计算云锡矿工的氡致肺癌危险系数。     

对Hazelton等提出的云锡矿工肺癌主要危险来自砷的商榷

Using two-stage clonal expansion model with data-base provided by Lubin, WD Hazehon et al indicated the high risk of arsenic, but not radon, in the etiology of Yunnan tin miner' s lung cancer. The author of this review iterated the problems in the data-base of Lubin,and considered that it may result in low estimate for the risk of radon in paper of Hazehon et al. Attributable risk was estimated by them with changing exposure patterns of each individual, but the efficacy of this two-stage model will be violated by the invariability of appointed radon/arsenic exposures. Risk comparison was used to distinguish the contribution from radon/arsenic, which was hampered by the high correlation between their joint exposures. As Lubin, Hazehon et al neglected the confounding from environmental arsenic pollution in early years. From all of above, their viewpoint is worth to be deliberated.     

室内氡与肺癌关系研究

目的 直接调查居室水平氡浓度对居民肺癌危险度的影响，并与由矿工受照结果推导的结论相比较。方法 在甘肃省平凉、庆阳两地区进行病例－对照研究。该地区居民稳定而室内氡水平较高。肺癌病例必须是在1994年1月至1998年4月期间诊断，年龄在30－75岁之间，居住在平凉和庆阳两地区的居民。根据人口调查资料随机选取对照，对照要在年龄、性别、地区方面与病例相匹配。在过去5－30年期间，凡住过两年以上的房间都布放了氡探测器。氡测量涵盖了77％的照射周期。结果 病例居室的平均氡浓度为230．4Bq/m^3(n=768)，对照为222．2Bq/m^3(n=1659)。居民肺癌危险度随室内氡水平的增高有所上升（P＜0．001）。根据线性模型，对全部研究个体而言，在100Bq/m^3情况下，附加比值比（EOR）为0.19(95% CI:0.05,0.47)。对测量涵盖了100％照射周期的个体，为0．31（95％CI：0．10，0．81）。在对照射的不确定度进行调整后，估算值可增加70％。结论 研究结果证明室内水平氡照射会增加肺癌危险度，增加值等于或超过从矿工数据外推的结果。     

Mortality from cancers of the extra-thoracic airways in relation to radon progeny in the Wismut cohort, 1946–2008

Abstract

Purpose: Inhalation of radon progeny can cause high lung and respiratory tract radiation doses. The aim of this paper was to examine the relationship between radon progeny and cancers of the extra-thoracic airways in the German uranium miner cohort for an extended follow-up through 2008.

Methods: The cohort included 58,690 workers employed between 1946 and 1989 at the Wismut company. Exposure to radon progeny in Working Level Months (WLM) was determined from a comprehensive job-exposure matrix. The mean (max) cumulative exposure to radon among exposed cohort members (86%) was 280 WLM (3,224 WLM). Internal Poisson regression models were applied to estimate the linear Excess Relative Risk (ERR) per unit of cumulative exposure to radon.

Results: A small increase in the mortality from all cancers of the extra-thoracic airways combined with increasing cumulative exposure to radon was found (ERR/100 WLM = 0.036, p = 0.12), based on 234 deaths. The estimated ERR per 100 WLM for relevant cancer sub-groups were: 0.017 (p > 0.5) larynx (n = 94); 0.077 (p = 0.20) pharynx (n = 74); and 0.030 (p > 0.5) tongue and mouth (n = 55).

Conclusion: Results indicated a small but not statistically significant increase in mortality from cancers of the extra-thoracic airways in relation to radon. Low statistical power and uncontrolled confounding were limitations of this study.     

Comparisons of lung tumour mortality risk in the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: support for the ICRP lung model

PURPOSES: To estimate the ratio of risks for exposure to radon progeny relative to low-LET radiation based on human lung cancer data, taking account of possible time and age variations in radiation-induced lung cancer risk. MATERIALS AND METHODS: Fitting two sorts of time- and age-adjusted relative risk models to a case-control dataset nested within the Colorado Plateau uranium miner cohort and to the Japanese atomic (A)-bomb survivor mortality data. RESULTS: If all A-bomb survivors are compared with the Colorado data, there are statistically significant (two-sided p < 0.05) differences between the two datasets in the pattern of the variation of relative risk with time after exposure, age at exposure and attained age. The excess relative risk decreases much faster with time, age at exposure and attained age in the Colorado uranium miners than in the Japanese A-bomb survivors. If only male A-bomb survivors are compared with the Colorado data, there are no longer statistically significant differences between the two datasets in the pattern of variation of relative risk with time after exposure, age at exposure or attained age. There are no statistically significant differences between the male and female A-bomb survivors in the speed of reduction of relative risk with time after exposure, age at exposure or attained age, although there are indications of rather faster reduction of relative risk with time and age among male survivors than among female survivors. The implicit risk conversion factor for exposure to radon progeny relative to the A-bomb radiation in the male survivors is 1.8 x 10(-2) Sv WLM(-1) (95% CI 6.1 x10(-3), 1.1 x 10(-1)) using a model with exponential adjustments for the effects of radiation for time since exposure and age at exposure, and 1.9 x 10(-2) Sv WLM(-1) (95% CI 6.2 x 10(-3), 1.6 x 10(-1)) using a model with adjustments for the effects of radiation proportional to powers of time since exposure and attained age. Estimates of the risk conversion factor calculated using variant assumptions as to the definition of lung cancer in the Colorado data, or by excluding miners for whom exposure estimates may be less reliable, are very similar. The absence of information on cigarette smoking in the Japanese A-bomb survivors, and the possibility that this may confound the time trends in radiation-induced lung cancer risk in that cohort, imply that these findings should be interpreted with caution. CONCLUSIONS: There are no statistically significant differences between the male A-bomb survivors data and the Colorado miner data in the pattern of variation of relative risk with time after exposure and age at exposure. The risk conversion factor is very close to the value suggested by the latest ICRP lung model, albeit with substantial uncertainties.     

用差异显示法研究云锡矿工肺癌组织相关基因

目的为探讨矿工肺癌发生的机理,作者研究了与云锡矿工肺癌组织相关的基因。方法以云南锡矿工肺癌切除术的癌组织和正常肺组织为样品,用差异显示法比较两种组织差异表达基因,并将其克隆测序。结果在肺癌组织和同例正常肺组织中发现有３０个表达差异的基因片段。其中,１６个片段仅在肺癌组织中表达而不在正常组织中表达;１４个片段仅在正常组织中表达而不在肺癌组织中表达;测定了６个片段的序列。ＣＧ２、ＣＧ７、ＣＧ８、ＣＡ５和ＣＣ６５个序列在Ｇｅｎｂａｎｋ中未查到有７５％同源的序列,被认为是新序列并在Ｇｅｎｂａｎｋ中登录。ＣＧ３与人核糖体蛋白Ｌ２７ａ有９５％同源性。结论在矿工肺癌组织和同例正常肺组织中有已知和未知的表达差异基因存在。     

应用mRNA差异显示法初步研究肺癌相关基因

目的：研究高氡暴露地区居民肺癌组织中相关未知基因，探讨肺癌发生的机理。方法：应用mRNA差异显示方法从同一例肺癌和正常肺组织中选出有表达差异的基因片段，经反向Northern Blot杂交，将肺癌组织表达呈阳性的片段而正常肺组织呈阴性的片段进行克隆测序。结果：7条差异片段经克隆测序后发现，其中NA7与Genbank EST中的A1208667序列同源性达95％以上，NG2与5条基因序列同源性高达98％，而CA1可能是一个新的差异基因片段，结论：从高氡暴露地区居民肺癌和正常组织中获得3条可能与肿瘤相关的基因片段。     

Doses and lung cancer risks from exposure to radon and plutonium

Abstract

Purpose: Epidemiological studies of the French uranium miners and the plutonium workers at the Mayak nuclear facility have provided excess relative risk (ERR) estimates per unit absorbed lung dose from alpha radiation. The aim of this paper was to review these two studies and to derive values of the relative biological effectiveness (RBE) of alpha particles for the induction of lung cancer.

Materials and methods: We examined and compared the dosimetry assumptions and methodology used in the epidemiological studies of uranium miners and the plutonium workers. Values of RBE were obtained by comparing risk coefficients including comparison of lifetime risks for a given population. To do this, preliminary calculations of lifetime risks following inhalation of plutonium were carried out.

Results and conclusions: Published values of risk per unit dose following inhalation of radon progeny and plutonium were in agreement despite the very different dose distributions within the lungs and the different ways the doses were calculated. Values of RBE around 10–20 were obtained by comparing ERR values, but with wide uncertainty ranges. Comparing lifetime risks gave similar values (10, 19 and 21). This supports the use of a radiation weighting factor of 20 for alpha particles for radiation protection purposes.     

基于EPA/BEIR-VI模型的我国居室内氡致肺癌风险估计

目的:估计我国居室内氡导致的居民肺癌归因份额。方法:利用较为权威且适用的EPA/BEIR-VI风险模型,基于我国2015年肺癌死亡率、全死因死亡率以及有代表性的吸烟率和居室内氡平均浓度,预测我国居室内氡浓度水平致肺癌死亡风险。结果:非吸烟男性人群居室内氡致肺癌死亡超额相对危险(ERR)高于吸烟人群,且达到年龄为50岁时...     

湖南A铀矿氡和氡子体及矿工肺癌

本文分析了湖南A铀矿井下氡子体对矿工的危害。早年井下氡和氡子体浓度超过限值20多倍.自建矿至1985年底, 主要工种的氡子体累积暴露量平均200WLM。观察2149名1971年前下井老工人, 1970～1985(15年)肺癌死亡11例, 肺癌粗死亡率35.14×10^-5, 特异死亡率24.07×10^-5, SMR=3.17。肺癌平均井下工龄18.5年。肺癌绝对危险系数5.58×lO^-6人年·wLM^-3, 特异相对危险系数5.03×l0^-2WLM^-1。剂量效应分析表明, 肺癌危硷随氡子体累积暴露量增加而增高。     

Radon: is it a problem?

Radon gas is a major source of radiation exposure to the general public. Radon-222 is a product of uranium-238, present in varying concentrations in all soils. Radon enters buildings from soil, water, natural gas, and building materials. Its short-lived breakdown products, termed "radon daughters," include alpha-emitting solids that can deposit in the lungs. Firm evidence links lung cancer risk in miners with high exposure to radon daughters. The amount of risk associated with the much lower but chronic doses received in buildings is difficult to establish. By some extrapolations, radon daughters may be responsible for a significant number of lung cancer deaths. The existence or extent of synergism with smoking is unresolved. Local conditions can cause high levels of radon in some buildings, and measures that reduce indoor radon are of potential value.     

Health effects of radon: A review of the literature

Purpose:?Radon is natural radioactive noble gas that can be found in soil, water, outdoor and indoor air. Exposure to radon accounts for more that 50% of the annual effective dose of natural radioactivity. The purpose of the current review is to summarize recent literature and evaluate the weight of evidence on the adverse health effects of radon.

Conclusions:?Radon is an established human lung carcinogen based on human epidemiological data supported by experimental evidence of mutagenesis studies in cell culture and laboratory animals. Extrapolation from cohort studies on miners suggested that radon is the second leading cause of lung cancer death after tobacco smoke. The majority of studies on the relationship between radon and other types of cancers showed weak or no association. Low levels of radon can be found in drinking water; however, radon released during water usage adds small quantities to indoor radon concentration. Studies showed that the risk of stomach cancer and other gastrointestinal malignancies from radon in drinking water is small. Studies of the genetic and cytogenetic effects of indoor radon yielded equivocal results; while radon exposure in miners induces gene mutations and chromosomal aberrations. Numerous in vitro cytogenetic studies demonstrated that radon induces different types of genetic and cytogenetic damage that is likely to play a role in radon lung carcinogenesis.     

Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation

PURPOSE: To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated. MATERIALS AND METHODS: Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies. RESULTS: For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow. CONCLUSIONS: The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.     

Lung cancer epidemiology, risk factors, and prevention

The greatest risk by far for developing lung cancer is cigarette smoking, but age, radon exposure, environmental pollution, occupational exposures, gender, race, and pre-existing lung disease also are important contributors. However, not all people with these risk factors develop lung cancer, and some without any known risk factor do, indicating the importance of genetic influences. Future advances in understanding and treating lung cancer will be based on genetic analysis. The most effective preventive measure is to never start or to stop cigarette smoking.     

Transformation of lung cells from inhalation of radon daughters in dwellings: a preliminary study

There is now world-wide concern for the quantification of lung cancer risk due to indoor radon, but the recent estimates are based on epidemiological studies of miners alone. The present attempt is a preliminary study of the alteration of lung stem cells irradiated by alpha particles emitted by radon daughters. Local energy deposited has been calculated for alpha particles, emitted from radon daughters lining the mucous layer in the respiratory tracts. This calculation has then been followed by dose evaluation and estimation of transformation of lung cells as a function of age. Mean life span of the stem cells was varied between 5 and 45 years to simulate living conditions in different environments. The cumulative fraction of transformed cells after 40 and 70 years has been calculated for radon concentration in the range 23-230 Bq/m3. Increase of the fraction of transformed cells with radon concentration was exponential. It has been assumed that causes other than radiation increase the rate of cell death of mature and stem lung cells, and hence the turnover of stem cells to replace them. It is concluded that the rate of transformation of cells is small for low radon concentration even late in age for non-polluted environments. For radon concentrations of 50 and 100 Bq/m3 the fractions of transformed cells are 0.2 and 6 per cent, respectively for an exposure time of 70 years.     

The influence of uncertainties of radon exposure on the results of case-control epidemiological study

Abstract

Purpose: Simulation of large-scale epidemiological study to identify the influence of uncertainties of radon exposure assessment on the excess relative risk of lung cancer.

Materials and methods: Analysis of sources of uncertainties arising during radon epidemiologic case-control studies. Assessment of the uncertainties due to influence of long-term variations of radon concentration, exposure to radon in other places of human presence, except dwellings, quality of radon concentration measurements etc. Simulation by Monte Carlo technique of radon epidemiologic study, comparable to the pooled European radon case-control study, and assessment of uncertainties, which affect the evaluation of dose-effect dependence.

Results: The uncertainties of personal exposure to radon are generally caused by the combined effect of long-term variations of radon concentration and the differences in the levels of radon concentration in homes and other places of human presence. The logarithmic standard deviation of this uncertainty is from 0.70 to 0.90. This value is ～2 times higher than the uncertainty, applied for correction of the results in the pooled European radon case-control study. It is shown that for σ_err?<?1.0 regression calibration technique allows to make full correction of the uncertainty. The error in assessment of uncertainties of the exposure to radon concentration in the pooled European radon case-control study has led to an underestimation of excess relative risk of lung cancer incidence at least by 1.5 times.

Conclusion: The error in an assessment of uncertainties of radon exposure in the pooled European radon case-control study has led to an underestimation of relative risk of lung cancer incidence at least by 1.5 times.     

典型非铀矿山工人氡危险认知研究

目的 调查非铀矿山工人对氡所致健康危害的认知水平及影响因素。方法 采用当面填写调查表或询问方式调查了9个省区24个矿山的2836名矿工。结果 13.3%的矿工知晓氡,其中,29.0%的人知道氡的来源,8.5%的矿工对氡危害有一定认识,仅有1.8%的矿工对氡致健康危害有正确认知。在影响非铀矿山工人对氡致健康危害正确认知水平的因素中,受教育程度与氡认知水平正相关;正式职工对氡的认知水平优于临时雇用工人;性别、年龄、从事现工作的工龄等因素对氡认知水平没有明显影响;不同省区及矿山的氡认知水平不同。结论 我国非铀矿山矿工对氡危险认知水平较低,应进一步落实并规范《职业病防治法》规定的职业危害告知义务。     

空气质量指数与室外氡子体浓度的相关性研究

目的 研究不同空气质量指数(air quality index,AQI)下氡子体的分布特征,评价雾霾天气暴露人群的健康风险。方法 利用EQF3120测量仪监测放射性核素氡及其子体浓度,空气质量指标数据由苏州工业园区环境监测站提供。运用SPSS 16.0对氡及其子体与空气质量指标等数据进行统计描述、主成分分析及简单相关分析。运用氡剂量计算公式估算环境氡暴露致肺部区域有效剂量。结果 苏州市工业园区冬季雾霾天气结合态氡子体与NO₂、SO₂、O₃、PM10和PM2.5均存在相关关系,²¹⁴Bi与其相关系数分别为0.741、0.681、-0.431、0.597和0.675;且结合态氡子体与PM2.5的相关系数>与PM10的相关系数;当AQI>200,居民在室外接收氡及其短寿命子体的有效剂量为0.63 mSv/年。结论 随着AQI的增大,结合态氡子体浓度增大,未结合态氡子体浓度变化不大;雾霾天气增加了暴露人群吸入氡的辐射风险。     

非铀矿山氡致肺癌危险相关参数的调查

目的 调查非铀矿山从业人员职业氡暴露致肺癌危险估计所需参数。方法 对选自9省区13类24座矿山的2836名矿工,采用当面填写调查表或询问方式,调查了职业氡暴露致肺癌危险估计所需要的基本参数,包括平均工龄、开始暴露年龄、吸烟情况等。采用描述性统计方法进行分析。结果 非铀矿山在职职工年龄为17~72岁,平均年龄为(36.9±8.0)岁。非铀矿工受教育程度低,3%为文盲,58%接受了小学或初中教育,受过大专及以上教育的人仅7%。非铀矿工中75%为农民工,少数民族矿工的比例为16%。临时工开始职业氡暴露的年龄为(29.6±8.0)岁。到调查时,在矿山工作的工龄为(6.7±6.8)年,工龄中位数为4.1年,工龄≥5 年工人占46.7%。3.4%的在职职工在18岁以前开始矿山工作。有17.5%的工人报告每日工作时间大于8 h。被调查者中,58.0%(43.0%~83.0%)男性矿工为当前吸烟者,平均从20岁开始吸烟,吸烟量中位数为16支。 当前吸烟率与年龄有关,15~19岁矿工的吸烟率最高,达69.2%。煤矿工当前吸烟率为49.0%,非煤矿山工人为62.5%,两者差异具有统计学意义(χ²=59.1,P<0.01)。不同省区男性矿工吸烟率明显不同(χ²=1200,P<0.01)。煤矿工报告使用机械通风情况明显优于非煤矿山矿工(χ²=80.7,P<0.01)。结论 非铀矿山一线工人中75%为农民工。矿工约在30岁开始井下职业高氡暴露,但有3%的矿工在18岁以前开始从业,接近一半矿山工人工龄为5年及以上,男性矿工当前吸烟率无异于一般男性人群。     

The radon issue: Considerations on regulatory approaches and exposure evaluations on the basis of recent epidemiological results.

Recent epidemiological results have shown consistent statistically significant increases of lung cancer risk due to exposure to radon in dwellings at moderate levels of exposure, and a strong synergism with cigarette smoking. These results are summarized and discussed in relation to their possible implications for the regulatory control of radon and for future policies for the control of radon risk.