Investing in prospective cohorts for etiologic study of occupational exposures.

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis.

Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.

Differential effects of smoking on lung cancer mortality before and after household stove improvement in Xuanwei, China.

BACKGROUND: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China. METHODS: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement. RESULTS AND CONCLUSION: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000).

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

Lung cancer risk from residential radon: meta-analysis of eight epidemiologic studies.

BACKGROUND: Studies of underground miners exposed to radioactive radon and its decay products have found that exposure increases risk of lung cancer. Consequently, when radon was found to accumulate in houses, there was concern about the public health impact from exposure to a known carcinogen. Estimates on the basis of studies of underground miners suggest that indoor radon may account for 6000-36,000 lung cancer deaths each year in the United States. Because of differences between working in underground mines and living in houses, estimates are subject to major uncertainties. Numerous case-control studies were launched to assess directly the lung cancer risk from indoor radon. Some studies report positive or weakly positive findings, while others report no increased risk. Thus, the potential hazard from indoor radon remains answered only indirectly through miner studies, experimental animal studies, and cellular studies. PURPOSE: To provide more information on the risk of lung cancer from indoor radon, we conducted a meta-analysis of all case-control studies that included at least 200 case subjects each and that used long-term indoor radon measurements. METHODS: Eight studies were available and included a total of 4263 lung cancer case subjects and 6612 control subjects. From the published results of each study, confounder-adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for categories of radon concentration were obtained, and weighted linear regression analyses were performed. RESULTS: The combined trend in the RR was significantly different from zero (two-sided P = .03), and an estimated RR of 1.14 (95% CI = 1.0-1.3) at 150 Bq/m3 was found. An influence analysis indicated that no single study dominated the combined results. The exposure-response trend was similar to model-based extrapolations from miners and to RRs computed directly from miners with low cumulative exposures. However, there were significant differences in the study-specific estimates of the exposure response (two-sided P < .001), which were not explained by study differences in percent of the defined exposure interval covered by radon measurements, mean number of residences per subject, and other factors. CONCLUSIONS: Meta-analyses are valuable for identifying differences among studies and for summarizing results, but they should be interpreted cautiously when expected RRs are low as with indoor radon exposure, when there is study heterogeneity and where there is the potential for confounding and exposure misclassification. Nonetheless, the results of this meta-analysis suggest that the risk from indoor radon is not likely to be markedly greater than that predicted from miners and indicate that the negative exposure response reported in some ecologic studies is likely due to model misspecification or uncontrolled confounding and can be rejected. IMPLICATIONS: Until ongoing case-control studies of indoor radon are completed and the data are pooled and analyzed, the studies of underground miners remain the best source of data to use to assess risk from indoor radon. This meta-analysis provides support for their general validity.

Assessment of lung cancer risk factors by histologic category.

The patterns of risk by histologic type of lung cancer were analyzed with the use of data from a large hospital-based case-control study (7,804 cases and 15,207 controls) of lung cancer performed in Western Europe. Relative risks (RR) increased with duration of cigarette use for all histologic types, although the gradients of risk were greater for Kreyberg I cell types, particularly squamous cell carcinoma (SCC), than for adenocarcinoma (AC). Risks also declined more sharply with years since cessation of smoking for all Kreyberg I cell types, in particular for SCC, rather than for AC. After adjustment for duration of use, the RR associated with number of cigarettes smoked per day, frequency and depth of inhalation, and fraction of cigarette consumed were not consistently different by cell type, suggesting that intensity-related measures of cigarette exposure have less effect on cell type than duration-related factors. Among those who never smoked there were marked cell type differences by sex, with a greater proportion of AC compared to SCC for females (45 vs. 25%) than for males (35 vs. 33%). Review of limited work histories indicated that occupational associations also were more strongly related to Kreyberg I than to Kreyberg II tumors.

Lung cancer risk with cigar and pipe use.

Data from a large study of lung cancer (6,920 cases and 13,460 controls) conducted in Western Europe were analyzed to evaluate risks associated with cigar and pipe use among males. Relative to risks among nonsmokers, risks of lung cancer for cigar-only [relative risk (RR) = 2.9] and pipe-only (RR = 2.5) smokers were significantly elevated, but at levels below mixed cigarette and cigar (RR = 6.9) or pipe (RR = 8.1) users and cigarette-only (RR = 9.0) smokers. There were significant trends of increased risk of lung cancer with years of cigar and pipe use and with number of cigars and pipes smoked per day. The increases were seen most clearly among exclusive cigar or exclusive pipe users. Among cigar-only smokers risks increased with greater frequency and depth of inhalation and decreased with years since cessation of use, whereas among pipe-only and mixed smokers trends in risks were not seen with these variables. The histology of the lung cancers among cigar-only and pipe-only smokers closely paralleled the cell type distribution of cases smoking cigarettes only; about 75% were squamous or oat (small) cell carcinomas and less than 10% were adenocarcinomas, in contrast to the findings in nonsmokers, in whom 41% were classified as squamous or oat (small) cell carcinoma versus 37% adenocarcinoma. These results clearly demonstrate a link between cigar and/or pipe use and risk of lung cancer and suggest that differences in risk levels between cigar-only, pipe-only, mixed, and cigarette-only smokers are strongly related to inhalation practices.

Dark tobacco and lung cancer in Cuba.

A retrospective epidemiologic study of 826 cytologically and/or histologically confirmed lung cancer cases (219 females and 607 males), 979 hospital controls, and 539 neighborhood controls was undertaken in Havana, Cuba, to investigate whether the high lung cancer mortality rates in this country could be explained by the cigarette and cigar consumption habits, including the smoking of dark-tobacco cigarettes. Relative risk(s)(RR) of lung cancer among cigarette smokers were 7.3 in women and 14.1 in men and increased consistently with various measures of exposure to smoke. The findings suggested that duration of smoking, daily number of cigarettes consumed, and inhalation practices have independent effects. Most Cubans smoked dark tobacco. RR were higher for dark-tobacco users than for light-tobacco users (RR = 8.6 vs. 4.6 for women and 14.3 vs. 11.3 for men), but the differences were reduced after adjustment for amount smoked. Cigarette smoking was associated with all histologic types of lung cancer, although the risk for adenocarcinoma was lower than that for the other types. Men who smoked exclusively cigars had a fourfold risk of lung cancer. Mixed smokers (i.e., cigar and cigarette smoker) had a greater RR than cigarette-only smokers (15.0 vs. 14.1), which was perhaps related to the unusually deep and frequent inhalation of cigar smoke. The data support the hypothesis that smoking patterns account for the higher lung cancer mortality in Cuba than in other Latin American countries.

Lung cancer and other causes of death among licensed pesticide applicators.

The mortality experience of a cohort of 3,827 white men licensed to apply pesticides in Florida was evaluated to investigate health effects associated with chronic exposure to pesticides. Although the overall standardized mortality ratio (SMR) for these structural pest control workers was not significantly elevated (SMR = 103), excess deaths were observed for leukemia, particularly acute myeloid leukemia (3 observed vs. 0.9 expected), and cancers of the brain (SMR = 200) and lung (SMR = 135). The risk of lung cancer rose with the number of years licensed with SMR of 101, 155, and 289 among those licensed for less than 10 years, for 10-19 years, and for 20 years or more, respectively. Ratios of directly adjusted rates showed similar patterns with observed-to-expected ratios of 100, 175, and 186 for the length of licensure categories. Mortality from lung cancer was greater among persons first licensed before age 40 (SMR = 234) than among those first licensed after age 40 (SMR = 115). Although information on tobacco use was not available, the increasing risk of lung cancer with number of years licensed and the capacity of certain pesticides to produce neoplasms in laboratory animals suggested that some pesticides may be carcinogenic in humans.

Cancer trends in a population at risk of acquired immunodeficiency syndrome.

Recent case reports have suggested that the acquired immunodeficiency syndrome (AIDS) may be associated with cancers other than Kaposi's sarcoma (KS). We have used the population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program to examine these relationships on a statistical basis by comparing the morbidity odds ratio (OR) and 95% confidence interval (CI) for specific cancer sites in pre- and post-AIDS time periods. Among never-married 20- to 49-year-old men, a surrogate group representing homosexual men, significant increases in the morbidity OR's for KS between 1973-80 and 1981-82 were apparent in the San Francisco standard metropolitan statistical area (OR: 51.8; CI: 18.6-143.6) and in other areas covered by the SEER Program (OR: 18.6; CI: 2.2-154.5). Furthermore, a significant increase was found in the morbidity OR for Burkitt-like lymphoma in the San Francisco metropolitan area (OR: 9.1; CI: 1.8-45.6). In San Francisco County (which includes the City of San Francisco), there was a 2,043-fold increase in the morbidity OR for KS and a fivefold increase for Burkitt-like lymphomas, but there were no significant changes for other cancers between 1973-79 and 1982. Similarly, no significant changes in morbidity OR's were observed for other cancers in the remaining SEER registries. These findings provided statistical support for the excess risk of Burkitt-like lymphoma in a group at risk of AIDS.

Residential radon exposure and lung cancer among nonsmoking women.

BACKGROUND: Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. PURPOSE: Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. METHODS: A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 non-smoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. RESULTS: Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L-1]). Radon levels greater than 4 pCi L-1 were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. CONCLUSIONS: The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. IMPLICATIONS: The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low.

Cancer following radiotherapy for peptic ulcer.

BACKGROUND: Radiotherapy for peptic ulcer was used between 1937 and 1965 to control excessive gastric acid secretions (mean dose, 14.8 Gy). Patients with this benign condition live many years after treatment and are at risk for late effects. PURPOSE: Our purpose was to investigate the risk of death from cancer following radiotherapy for peptic ulcer. METHODS: A mortality study was conducted of 3609 patients with peptic ulcer; 1831 were treated with radiation and 1778 were treated by other means. Extensive methods were used to trace patients. Radiation doses to specific organs were reconstructed from the original radiotherapy records. RESULTS: Nearly 70% of patients were found to have died. The average period of observation was 21.5 years (maximum 51 years). Compared with the general population, patients treated with or without radiation were at significantly increased risk of dying of cancer and non-malignant diseases of the digestive system. Risk of death due to heart disease was slightly higher following radiotherapy. Cancers of the stomach, pancreas, lung, and prostate were increased in both irradiated and nonirradiated patients. Radiotherapy was linked to significantly high relative risks (RRs) for all cancers combined (RR = 1.53; 95% confidence interval [CI] = 1.3-1.8), for cancers of the stomach (RR = 2.77; 95% CI = 1.6-4.8), pancreas (RR = 1.87; 95% CI = 1.0-3.4), and lung (RR = 1.70; 95% CI = 1.2-2.4), and for leukemia (RR = 3.28; 95% CI = 1.0-10.6). Radiation combined with surgery, or given to treat gastric ulcer, appeared to increase the risk of stomach cancer 10-fold, which was greater than the sum of individual effects. Patients with gastric ulcers were at higher risk for stomach cancer than patients with duodenal ulcers. CONCLUSIONS: Patients with peptic ulcer are at increased risk of dying of cancer, related in part to lifestyle factors and treatment. Radiotherapy and surgery together appear to induce carcinogenic processes that greatly enhance the development of stomach cancer. The risk of radiation-induced stomach cancer was 0.25 extra deaths per 10,000 persons per year per Gy, somewhat lower than reported in other studies. High-dose radiation may have increased the risk of pancreatic cancer, a condition rarely found elevated in irradiated populations, but misclassified death notices may have contributed to the excess. Cancer mortality remained high for up to 50 years, indicating that radiation damage may persist to the end of life.

Radon and cancers other than lung cancer in underground miners: a collaborative analysis of 11 studies.

BACKGROUND: Exposure to the radioactive gas radon and its progeny (222Rn and its radioactive decay products) has recently been linked to a variety of cancers other than lung cancer in geographic correlation studies of domestic radon exposure and in individual cohorts of occupationally exposed miners. PURPOSE: This study was designed to characterize further the risks for cancers other than lung cancer (i.e., non-lung cancers) from atmospheric radon. METHODS: Mortality from non-lung cancer was examined in a collaborative analysis of data from 11 cohorts of underground miners in which radon-related excesses of lung cancer had been established. The study included 64,209 men who were employed in the mines for 6.4 years on average, received average cumulative exposures of 155 working-level months (WLM), and were followed for 16.9 years on average. RESULTS: For all non-lung cancers combined, mortality was close to that expected from mortality rates in the areas surrounding the mines (ratio of observed to expected deaths [O/E] = 1.01; 95% confidence interval [CI] = 0.95-1.07, based on 1179 deaths), and mortality did not increase with increasing cumulative exposure. Among 28 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (O/E = 1.33; 95% CI = 1.16-1.52) and liver (O/E = 1.73; 95% CI = 1.29-2.28) and statistically significant decreases for cancers of the tongue and mouth (O/E = 0.52; 95% CI = 0.26-0.93), pharynx (O/E = 0.35; 95% CI = 0.16-0.66), and colon (O/E = 0.77; 95% CI = 0.63-0.95) were observed. For leukemia, mortality was increased in the period less than 10 years since starting work (O/E = 1.93; 95% CI = 1.19-2.95) but not subsequently. For none of these diseases was mortality significantly related to cumulative exposure. Among the remaining individual categories of non-lung cancer, mortality was related to cumulative exposure only for cancer of the pancreas (excess relative risk per WLM = 0.07%; 95% CI = 0.01-0.12) and, in the period less than 10 years since the start of employment, for other and unspecified cancers (excess relative risk per WLM = 0.22%; 95% CI = 0.08-0.37). CONCLUSIONS: The increases in mortality from stomach and liver cancers and leukemia are unlikely to have been caused by radon, since they are unrelated to cumulative exposure. The association between cumulative exposure and pancreatic cancer seems likely to be a chance finding, while the association between cumulative exposure and other and unspecified cancers was caused by deaths certified as due to carcinomatosis (widespread disseminated cancer throughout the body) that were likely to have been due to lung cancers. This study, therefore, provides considerable evidence that high concentrations of radon in air do not cause a material risk of mortality from cancers other than lung cancer. IMPLICATIONS: Protection standards for radon should continue to be based on consideration of the lung cancer risk alone.

Risk factors for breast cancer in women in northern Alberta, Canada, as related to age at diagnosis.

A population-based case-control study involving interviews with 577 female breast cancer patients and 826 controls in northern Alberta. Canada, revealed that some determinants of breast cancer varied according to age. Among women under age 45, risk factors included a younger age at menarche, late age at last birth, high parity, and recent use of oral contraceptives. At older ages risk was related to natural as opposed to surgical menopause, late age at first birth, low parity, late age at natural menopause, and tonsillectomy. At all ages there was an increased risk of breast cancer associated with difficulty in conceiving, benign breast disease, not having breast fed, and a history of breast cancer among mothers or sisters. For some variables the age differences were pronounced; the combination of low parity and late age at first birth was associated with a sevenfold increase in breast cancer risk at risk at ages 55-80 but a slight decrease at ages under 45. The effect of tonsillectomy steadily increased with age and represents a new lead, but certain features of the data suggest that the link to oral contraceptives among among younger women and the inverse relation to breast feeding at all ages may not be causal. Even though design limitations (cases interviewed in a different setting from controls) appeared not to influence conclusions, the results may have been subjected to interview bias and thus should be interpreted cautiously.

Lung cancer in radon-exposed miners and estimation of risk from indoor exposure.

BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners.

Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure.

BACKGROUND: Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. METHODS: Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. RESULTS: Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. CONCLUSIONS: In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL.

Quantitative evaluation of the radon and lung cancer association in a case control study of Chinese tin miners.

Studies of underground miners have consistently shown an increased risk of lung cancer with cumulative exposure to radon-222 and its decay products. Although the deleterious effects of high radon exposure are clear, questions regarding the shape of the exposure-response relationship, and the effects of time factors such as attained age, time since exposure and early age at first exposure, the effect of exposure rate, and the joint association of radon exposure and tobacco use have not yet been fully clarified. This report considers these questions by fitting various models for the relative odds of disease to 74 male lung cancer cases who were diagnosed between 1981 and 1984 and were alive in 1985 and an equal number of controls. All subjects are current or past employees of the Yunnan Tin Corporation, Gejiu City, China, who reside in the local area. Workers were interviewed to obtain information on work history, from which radon exposure in cumulative working level months and arsenic exposure were estimated, and on tobacco use. Results indicate that excess relative risk increases by 1.7% per cumulative working level month [95% confidence interval (0.5, 5.4)]. The linear exposure response relationship significantly declines with year since last radon exposure (P = 0.02). The risk trend also declines with increasing exposure rate (P = 0.001), indicating that long duration of exposure at a low rate may be more deleterious than short duration of exposure at a high rate. A unique aspect of this study population is the very early ages at first radon exposure for many of the workers, about 37% of the radon-exposed workers were first exposed under the age of 13 years. The analysis shows no modification of the radon lung cancer relationship with age at first exposure. These patterns of risk with radon exposure are generally consistent with those reported in the recent National Academy of Sciences' Biological Effects of Ionizing Radiations IV report. The primary method of tobacco consumption in this area of China is by waterpipe. Lung cancer risk increases with pipe-years of use. The joint analysis of tobacco use and radon exposure supports the Biological Effects of Ionizing Radiations IV conclusion that the most likely model is between additive and multiplicative. The variations of the radon lung cancer relationship by years since last exposure and exposure rate are not affected by adjustment for arsenic exposure.

Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group.

We estimated the risk of thyroid cancer among 9170 patients who had survived 2 or more years after the diagnosis of a cancer in childhood. As compared with the general population, patients had a 53-fold increased risk (95% confidence interval, 34-80). Risk increased significantly with time since treatment for the initial cancer (P = 0.03). Detailed treatment data were obtained for 23 cases and 89 matched controls from the childhood cancer cohort. Sixty-eight % of the thyroid cancers arose within the field of radiation. Radiation doses to the thyroid of greater than 200 cGy were associated with a 13-fold increased risk (95% confidence interval, 1.7-104). The risk of thyroid cancer rose with increasing dose (P less than 0.001), but this was derived almost entirely from the increase from less than 200 to greater than 200 cGy. The risk of thyroid cancer did not decrease, however, at radiation doses as high as 6000 cGy.

Adjusting lung cancer risks for temporal and spatial variations in radon concentration in dwellings in Gansu Province, China.

Our recent study in Gansu Province, China reported an increasing risk of lung cancer with increasing residential radon concentration that was consistent with previous pooled analyses and with meta-analyses of other residential studies (Wang et al., Am. J. Epidemiol. 155, 554-564, 2002). Dosimetry used current radon measurements (1-year track-etch detectors) in homes to characterize concentrations for the previous 30 years, resulting in uncertainties in exposure and possibly reduced estimates of disease risk. We conducted a 3-year substudy in 55 houses to model the temporal and spatial variability in radon levels and to adjust estimates of radon risk. Temporal variation represented the single largest source of uncertainty, suggesting the usefulness of multi-year measurements to assess this variation; however, substantial residual variation remained unexplained. The uncertainty adjustment increased estimates of the excess odds ratio by 50-100%, suggesting that residential radon studies using similar dosimetry may also underestimate radon effects. These results have important implications for risk assessment.