Radon exposure of the skin: I. Biological effects.

Radon progeny can plate out on skin and give rise to exposure of the superficial epidermis from alpha emitters Po-218 (7.7 MeV, range approximately 66 microm) and Po-214 (6 MeV, range approximately 44 microm). Dose rates from beta/gamma emitters Pb-214 and Bi-214 are low and only predominate at depths in excess of the alpha range. This paper reviews the evidence for a causal link between exposure from radon and its progeny, and deterministic and stochastic biological effects in human skin.Radiation induced skin effects such as ulceration and dermal atrophy, which require irradiation of the dermis, are ruled out for alpha irradiation from radon progeny because the target cells are considerably deeper than the range of alpha particles. They have not been observed in man or animals. Effects such as erythema and acute epidermal necrosis have been observed in a few cases of very high dose alpha particle exposures in man and after acute high dose exposure in animals from low energy beta radiations with similar depth doses to radon progeny. The required skin surface absorbed doses are in excess of 100 Gy. Such effects would require extremely high levels of radon progeny. They would involve quite exceptional circumstances, way outside the normal range of radon exposures in man.There is no definitive identification of the target cells for skin cancer induction in animals or man. The stem cells in the basal layer which maintain the epidermis are the most plausible contenders for target cells. The majority of these cells are near the end of the range of radon progeny alpha particles, even on the thinnest body sites. The nominal depth of these cells, as recommended by the International Commission on Radiological Protection (ICRP), is 70 microm. There is evidence however that some irradiation of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is also necessary for skin cancer induction. Alpha irradiation of rodent skin that is restricted to the epidermis does not produce skin cancer. Accelerator generated high energy helium and heavy ions can produce skin cancer in rodents at high doses, but only if they penetrate deep into the dermis. The risk figures for radiation induced skin cancer in man recommended by the ICRP in 1990 are based largely on x and beta irradiated cohorts, but few data exist below absorbed doses of about 1 Gy. The only plausible finding of alpha-radiation induced skin cancer in man is restricted to one study in Czech uranium miners. There is no evidence in other uranium miners and the Czech study has a number of shortcomings.This review concludes that the overall balance of evidence is against causality of radon progeny exposure and skin cancer induction. Of particular relevance is the finding in animal studies that radiation exposure of cells which are deeper than the inter-follicular epidermis is necessary to elicit skin cancer. In spite of this conclusion, a follow-on paper evaluates the attributable risk of radon to skin cancer in the UK on the basis that target cells for skin cancer induction are the cells in the basal layer of the inter-follicular epidermis-since this is the conservative assumption made by international bodies such as the International Commission on Radiological Protection (ICRP) for general radiological protection purposes.     

Malignant mesothelioma: attributable risk of asbestos exposure.

OBJECTIVES--To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS--Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS--Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS--Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.     

Estimating the incidence of lung cancer attributable to occupational exposure in Iran

Objective  

The aim of this study was to estimate the fraction of lung cancer incidence in Iran attributed to occupational exposures to the well-established lung cancer carcinogens, including silica, cadmium, nickel, arsenic, chromium, diesel fumes, beryllium, and asbestos.     

Estimation of cancer incidence and mortality attributable to alcohol drinking in china

Background  

Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005.     

Radon progeny exposure and lung cancer risk among non-smoking uranium miners

Studies of miners provide the basis for public health efforts to reduce residential radon progeny exposure. Because the preponderance of households do not have members who smoke indoors, studies of non-smoking miners contribute essential data for risk assessments for residential radon progeny exposure. We studied a cohort of 2,209 never-smokers who were underground uranium miners employed in the western U.S. from 1956 to the early 1990's and who participated in a screening program for lung cancer conducted by Saccomanno and colleagues. After determining the vital status and cause of death in the cohort, we conducted a nested case-control study of 55 lung cancer deaths in males and 3 age-matched controls for each case. The relative risk of lung cancer was 29.2 (95% CI 5.1, 167.2) for miners with greater than 1,450 WLM compared with those exposed to less than 80 WLM. Temporal factors affected risk, including average dose rate, which was inversely associated with lung cancer risk, and the length of time since last exposure, which was directly associated with decreased risk. As in studies of non-smokers and smokers combined, the exposure response relationship in never-smokers was consistent with a decreased slope at higher WLM, which resulted, in part, from an inverse dose rate effect.     

Estimation of attributable risk for case-control studies with multiple matching

Kuritz and Landis considered case-control studies with multiple matching and proposed an asymptotic interval estimator of the attributable risk based on Wald's statistic. Using Monte Carlo simulation, Kuritz and Landis demonstrated that their interval estimator could perform well when the number of matched sets was large (>or=100). However, the number of matched sets may often be moderate or small in practice. In this paper, we evaluate the performance of Kuritz and Landis' interval estimator in small or moderate number of matched sets and compare it with four other interval estimators. We note that the coverage probability of Kuritz and Landis' interval estimator tends to be less than the desired confidence level when the probability of exposure among cases is large. In these cases, the interval estimator using the logarithmic transformation and the two interval estimators derived from the quadratic equations developed here can generally improve the coverage probability of Kuritz and Landis' interval estimator, especially for the case of a small number of matched sets. Furthermore, we find that an interval estimator derived from a quadratic equation is consistently more efficient than Kuritz and Landis' interval estimator. The interval estimator using the logit transformation, although which performs poorly when the underlying odds ratio (OR) is close to 1, can be useful when both the probability of exposure among cases and the underlying OR are moderate or large.     

Population attributable risk for occupational cancer in Italy

Population studies estimating the proportion of cancer attributable to occupation (PAR) in different geographical areas in Italy are reviewed. Studies using lists of industrial activities and occupations which are known or suspected to entail exposure to lung carcinogens gave lung cancer PARs between 5% and 36%. Those using job-exposure matrices estimated PARs of 3%-53%, with most of the values ranging between 17 and 33%. For bladder cancer, PARs ranged between 4% and 24%. The uses and limitations of calculating population attribultable risk are discussed.     

Case-control study of thyroid cancer in Northern Italy: attributable risk.

BACKGROUND: The percentage of thyroid cancer cases attributable to specific risk factors can be calculated to focus preventive strategies. The per cent population attributable risks (PAR) for thyroid cancer were estimated in relation to history of benign thyroid diseases, history of radiotherapy, residence in endemic goitre areas and selected indicators of a poor diet, using data from a case-control study conducted between 1986 and 1992 in Northern Italy. METHODS: Cases were 399 histologically confirmed incident thyroid cancers and controls were 617 patients, admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. The PAR were computed on the basis of multivariate odds ratios (OR) and on the distribution of risk exposure among cases, assuming they are representative of the general population of cases. RESULTS: A history of benign thyroid disease accounted for 18.9% of cases, radiotherapy for 1.2%, residence for > or =20 years in endemic goitre areas for 2.4% of cases, and their combination for 21.7% of thyroid cancer cases; selected indicators of a poor diet accounted for 40.9% of thyroid cancer cases in this population. The combination of all factors considered explained over 57% of thyroid cancer cases in both sexes. The estimates for thyroid-related conditions were higher in women than men, whereas the opposite was true for dietary indicators. The overall PAR were somewhat higher in people aged > or =45 years (63.8%) than in younger subjects, and for follicular (69.1%) rather than papillary (53.7%) cancers. CONCLUSIONS: Exposure to a few simply identified and potentially modifiable risk factors or indicators (benign thyroid disease, residence in endemic goitre area and a poor diet) explained about 60% of thyroid cancer cases in this Italian population, indicating the theoretical scope for prevention.     

Lung cancer attributable to indoor radon exposure in france: impact of the risk models and uncertainty analysis

OBJECTIVE: The inhalation of radon, a well-established human carcinogen, is the principal-and omnipresent-source of radioactivity exposure for the general population of most countries. Scientists have thus sought to assess the lung cancer risk associated with indoor radon. Our aim here is to assess this risk in France, using all available epidemiologic results and performing an uncertainty analysis. METHODS: We examined the exposure-response relations derived from cohorts of miners and from joint analyses of residential case-control studies and considered the interaction between radon and tobacco. The exposure data come from measurement campaigns conducted since the beginning of the 1980s by the Institute for Radiation Protection and Nuclear Safety and the Directorate-General of Health in France. We quantified the uncertainties associated with risk coefficients and exposures and calculated their impact on risk estimates. RESULTS: The estimated number of lung cancer deaths attributable to indoor radon exposure ranges from 543 [90% uncertainty interval (UI) , 75-1,097] to 3,108 (90% UI, 2,996-3,221) , depending on the model considered. This calculation suggests that from 2.2% (90% UI, 0.3-4.4) to 12.4% (90% UI, 11.9-12.8) of these deaths in France may be attributable to indoor radon. DISCUSSION: In this original work we used different exposure-response relations from several epidemiologic studies and found that regardless of the relation chosen, the number of lung cancer deaths attributable to indoor radon appears relatively stable. Smokers can reduce their risk not only by reducing their indoor radon concentration but also by giving up smoking.     

Radon progeny exposure and lung cancer risk in New Mexico U miners: a case-control study

A case-control study was conducted to describe lung cancer risk in a cohort of New Mexico underground U miners. The subjects included 65 cases and 230 age-matched controls, most with exposures below 3.50 J h m-3 (1000 WLM). The risk for lung cancer was increased for all cumulative exposures to Rn progeny of 0.35 J h m-3 (100 WLM) or greater. The odds ratios were unchanged with control for cigarette smoking. With exclusion of subjects with exposures above 3.50 J h m-3 (1000 WLM), the estimated excess relative risk was 0.3% per mJ h m-3 (1.1% per WLM). The risk was greater for younger subjects and the data were consistent with a multiplicative interaction between cigarette smoking and exposure to Rn progeny.     

Estimation of cancer incidence and mortality attributable to overweight, obesity, and physical inactivity in China

The objective was to provide an evidence-based, systematic assessment of the burden of cancer due to overweight/obesity and physical inactivity in China. This study evaluated the proportion of cancers of colon, rectum, pancreas, breast (postmenopausal), endometrium, and kidney attributable to overweight [30 kg/m(2) > body mass index (BMI) ≥ 25 kg/m(2))/obesity (BMI ≥ 30 kg/m(2)) and physical inactivity in China in 2005. Data of prevalence of overweight/obesity and lack of physical activity were derived from cross-sectional surveys among representative samples of Chinese population, and data of relative risks on cancers were derived from meta-analyses or large-scale studies from China and East Asian populations. The attributable fractions were calculated by combining both data of prevalence and relative risks. In China in 2005, 0.32% of cancer deaths and 0.65% of cancer cases were attributable to overweight and obesity combined. Lack of physical activity was responsible for 0.27% of cancer deaths and 0.39% of cancer cases. Future projections indicate that the contribution of overweight and obesity to the overall cancer burden will increase in the next decades. The largest increased attributable fractions will be for endometrial cancer. The increase in attributable fractions would be greater in men and in rural populations. Although the current burden of cancer associated with overweight/obesity and physical inactivity is still relatively small in China, it is expected to increase in the future.     

Radon exposure and the risk of leukemia: a review of epidemiological studies

Since the 1990's, several authors estimated that radon inhalation may deliver a small amount of irradiation to the red bone marrow, and consequently may increase the risk of leukemia in humans. The objective of this review is to conduct a critical analysis of epidemiologic results currently available concerning the relationship between radon exposure and the risk of leukemia. Nineteen ecological studies, six miner cohort studies, and eight case-control studies published between 1987 and 2000 are included in this review. The limitations associated with each of these studies are discussed. The results of the ecological studies are relatively concordant and suggest an association between radon concentrations and the risk of leukemia at a geographic level. But these ecological studies present important limitations, and some are only crude analyses. Moreover, the results of the cohort and case-control studies, based on individual data, do not show any significant association between radon exposure and leukemia risk. Our conclusion is that the overall epidemiologic results currently available do not provide evidence for an association between radon exposure and leukemia.     

Risk and incidence of asthma attributable to occupational exposure among HMO members

Occupational asthma may account for a significant proportion of adult-onset asthma, but incidence estimates from surveillance of physician reports and workers' compensation data (0.9 to 15/100,000) are lower than expected from community-based cross-sectional studies of asthma patients. We conducted a prospective cohort study of 79,204 health maintenance organization members between the ages of 15 and 55 at risk for asthma. Computerized files, medical records, and telephone interviews were used to identify and characterize asthma cases. Evidence for asthma attributable to occupational exposure was determined from work-related symptoms and workplace exposure. The annual incidence of clinically significant, new-onset asthma was 1.3/1,000, and increased to 3.7/1,000 when cases with reactivation of previously quiescent asthma were included. Criteria for onset of clinically significant asthma attributable to occupational exposure were met by 21% (95% CI 12–32%) of cases giving an incidence of 71/100,000 (95% CI 43–111). Physicians documented asking about work-related symptoms in 15% of charts, and recorded suggestive symptoms in three cases, but did not obtain occupational medicine consultation, diagnose occupational asthma, report to the state surveillance program, or bill workers' compensation for any of them. These data suggest that the incidence of asthma attributable to occupational exposures is significantly higher than previously reported, and accounts for a sizable proportion of adult-onset asthma. Am. J. Ind. Med. 33:1–10, 1998. © 1998 Wiley-Liss, Inc.     

胃癌的环境与遗传危险因素及归因危险度分析

目的分析胃癌的环境与遗传危险因素并进行归因危险度评价。方法采用病例对照研究方法．对南京地区121例原发性胃癌病例进行环境危险因素调查，并对相关酶系基因多态性进行分析．综合评价环境危险因素及遗传危险性在胃癌发生中的归因危险度。结果在南京地区人群中，吸烟、食用腌制食品等两种环境危险因素与遗传危险因子细胞色素氧化酶P4502E1(CYP2E1)和N-乙酰化酶(NAT2)的基因型的人群综合归因危险度达69．7％。胃癌的发生主要是环境危险因素与内在遗传持点共同作用的结果。结论对胃癌的干预应同时考虑环境危险因素和遗传危险性，在了解个体遗传易感性的基础上，对其相应的环境危险因素进行干预，以达到Ⅰ级预防的目的。     

Radon and lung cancer risk: taking stock at the millenium

Radon is a well-established human carcinogen for which extensive data are available, extending into the range of exposures experienced by the general population. Mounting epidemiologic evidence on radon and lung cancer risk, now available from more than 20 different studies of underground miners and complementary laboratory findings, indicates that risks are linear in exposure without threshold. Radon is also a ubiquitous indoor air pollutant in homes, and risk projections imply that radon is the second leading cause of lung cancer after smoking. Recommended control strategies in the United States and other countries, which include testing of most homes and mitigation of those exceeding guideline levels, have been controversial. Further research is needed, drawing on molecular and cellular approaches and continuing the follow-up of the underground miner cohorts, and scientists should work toward constructing mechanistically based models that combine epidemiologic and experimental data to yield risk estimates with enhanced certainty.     

Interval estimation of the attributable risk for multiple exposure levels in case-control studies with confounders

The attributable risk (AR) is one of the most important and commonly-used epidemiological indices to assess the public health importance of an association between a risk factor and a disease. When the underlying risk factor has multiple exposure levels in the presence of confounders, we consider the case-control studies using random sampling to collect the cases and controls here. We develop four asymptotic interval estimators for AR, including the interval estimator using Wald's statistic, the interval estimator using the logarithmic transformation, the interval estimator using the logit transformation, and the interval estimator derived from a quadratic equation. We apply Monte Carlo simulation to evaluate the finite-sample performance of these interval estimators in a variety of situations. We demonstrate that given an adequately large sample size, all the estimators developed here can actually perform reasonably well. We note that the interval estimator using the logit transformation may be of limited use when the number of studied subjects is not large. We also note that the interval estimator using the logarithmic transformation can lose efficiency compared to the interval estimator using Wald's statistic or the interval estimator derived from a quadratic equation developed in this paper. Finally, we use the data taken from a case control study of the oral contraceptive use in myocardial infarction patients with various smoking levels to illustrate he practical usefulness of these estimators.