Indoor radon exposure and risk of lung cancer: a nested case-control study in Finland

BACKGROUND: Inhaled radon has been shown to cause lung cancer among underground miners exposed to very high radon concentrations, but the results regarding the effects of residential radon have been conflicting. PURPOSE: Our aim was to assess the effect of indoor radon exposure on the risk of lung cancer. METHODS: To investigate this effect, a nested case-control study was conducted in Finland. The subjects of the study were the 1973 lung cancer case patients (excluding patients with cancers of the pleura) diagnosed from January 1, 1986, until March 31, 1992, within a cohort of Finns residing in the same one-family house from January 1, 1967, or earlier, until the end of 1985 and 2885 control subjects identified from the same cohort and matched by age and sex. In September 1992, a letter was sent to all study subjects or proxy respondents explaining the purpose and methods of the study. After giving informed consent, the study participants were asked to fill out a questionnaire on smoking habits, occupational exposures, and other determinants of lung cancer risk and radon exposure. The odds ratio (OR) of lung cancer was estimated from matched and unmatched logistic regression analyses relative to indoor radon concentration assessed by use of a 12-month measurement with a passive alpha track detector. RESULTS. Five hundred seventeen case-control pairs were used in the matched analysis, and 1055 case subjects and 1544 control subjects were used in the unmatched analysis. The OR of lung cancer for indoor radon exposure obtained from matched analysis was 1.01 (95% confidence interval [CI] = 0.94-1.08) per 2.7 pCi/L (100 Bq m-3) after adjustment for the cigarette smoking status, intensity, duration, and age at commencement of smoking by subjects. For indoor radon concentrations 1.4-2.6, 2.7-5.3, 5.4-10.7, and 10.8-34.5 pCi/L (50-99, 100-199, 200-399, and 400-1277 Bq m-3, respectively), the matched ORs were 1.03 (95% CI = 0.84-1.26), 1.00 (95% CI = 0.78-1.29), 0.91 (95% CI = 0.61-1.35), and 1.15 (95% CI = 0.69-1.93), respectively, relative to the concentration below 1.4 pCi/L (0-49 Bq m-3). The unmatched analysis yielded similar results with somewhat smaller CIs. In the analyses stratified by age, sex, smoking status, or histologic type of lung cancer, no statistically significant indications of increased risk of lung cancer related to indoor radon concentration were observed for any of the subgroups. CONCLUSIONS: Our results do not indicate increased risk of lung cancer from indoor radon exposure. IMPLICATION: Indoor radon exposure does not appear to be an important cause of lung cancer.     

Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.     

Mechanistic model predicts a U-shaped relation of radon exposure to lung cancer risk reflected in combined occupational and US residential data

A mechanistically based cytodynamic two-stage (CD2) cancer model was shown recently to predict both ecologic US county data and underground-miner data on lung-cancer mortality (LCM) vs radon concentration, indicating biological plausibility of the apparent negative dose-response relation exhibited by the ecologic data. To further investigate this hypothesis, the CD2 model was fitted to combine age-specific LCM data vs estimated radon-exposure in white females of age 40+ years in 2821 US counties during 1950-1954 using new estimates of county-specific mean residential radon exposure, and in five cohorts of underground nonsmoking miners. The negative association of radon levels and corresponding county-level LCM rates apparent in women dying in 1950-1954 (11% of whom never smoked) was also apparent in women of age 60+ years (5% of whom never smoked). The CD2 fit obtained to the combined residential and occupational data was found to predict the combined data using biologically plausible parameter values, and also to predict inverse dose-rate effects exhibited in nonsmoking miner data to which the CD2 model was not fit. These results are consistent with the hypothesis that residential radon exposure has a nonlinear U-shaped relation to LCM risk, and that current linear extrapolation models substantially overestimate such risk.     

Avian exposure and risk of lung cancer in women in Missouri: population based case-control study

OBJECTIVE: To investigate the association, previously reported in three European studies, between ownership of pet birds and the risk of lung cancer. DESIGN: A population based case-control study with a structured questionnaire administered by telephone. SETTING: Missouri, a midwestern state in the United States with a population of about 5 million. SUBJECTS: All newly diagnosed cases of primary lung cancer in women aged 30-84 years in Missouri from 1 January 1993 to 31 January 1994 reported to the state cancer registry were invited to participate (n = 652); and 629 population based controls. MAIN OUTCOME MEASURES: Odds ratios were computed in relation to whether or not the study subject ever kept pet birds, the type of bird kept, and several measures of intensity or duration of exposure. Odds ratios were adjusted for smoking. RESULTS: The odds ratio (95% confidence interval) for the development of lung cancer associated with keeping pet birds was 0.84 (0.65 to 1.09). The results were similar for the type of pet bird kept, the number of birds kept, the location of the bird in the house, and the duration of ownership. CONCLUSION: The keeping of pet birds carries no excess risk for the development of lung cancer.     

Assessment of ecologic regression in the study of lung cancer and indoor radon

Ecologic regression studies conducted to assess the cancer risk of indoor radon to the general population are subject to methodological limitations, and they have given seemingly contradictory results. The authors use simulations to examine the effects of two major methodological problems that affect these studies: measurement error and misspecification of the risk model. In a simulation study of the effect of measurement error caused by the sampling process used to estimate radon exposure for a geographic unit, both the effect of radon and the standard error of the effect estimate were underestimated, with greater bias for smaller sample sizes. In another simulation study, which addressed the consequences of uncontrolled confounding by cigarette smoking, even small negative correlations between county geometric mean annual radon exposure and the proportion of smokers resulted in negative average estimates of the radon effect. A third study considered consequences of using simple linear ecologic models when the true underlying model relation between lung cancer and radon exposure is nonlinear. These examples quantify potential biases and demonstrate the limitations of estimating risks from ecologic studies of lung cancer and indoor radon.     

Occupational exposure of nonsmoking nightclub musicians to environmental tobacco smoke

This study assessed environmental tobacco smoke (ETS) exposures of nonsmoking musicians in nightclub environments using total suspended particulate (TSP), the ultraviolet absorbing fraction of TSP (UVPM), gaseous nicotine, saliva nicotine, saliva cotinine, and perceived smokiness as exposure/dose indicators. Measured exposures were as high or higher than those of other occupational groups studied. TSP ranged from 110 to 1714 micrograms/m3 (mean 502, SD 390 micrograms/m3). UVPM (mean 221, SD 95 micrograms/m3) was associated with gaseous and saliva nicotine concentrations. Paired-sample variation was much higher for TSP than for UVPM. Correlation of TSP with UVPM, gaseous nicotine, and saliva nicotine was poor. Paired-sample gaseous nicotine results were similar, with exposures of 28.0 to 50.0 micrograms/m3 (mean 37.1, SD 6.9 micrograms/m3), and were high compared with previous studies. These results suggested that nightclub musicians may be exposed to higher concentrations of ETS than some other occupational groups. Saliva nicotine results were consistent with those previously reported with regard to the range of values, large variation observed, and increase in saliva nicotine levels observable after only a few hours of exposure. Saliva nicotine results could not be correlated with other measures of exposure and did not appear to be a reliable biological indicator of absorbed dose. Saliva cotinine levels were comparable to other occupational groups studied, but were lower than previous findings for bartenders and waitresses. Levels ranged from 1.7 to 5.0 ng/mL (mean 3.4, SD 0.9 ng/mL), and increased with number of exposures during the workweek, but did not correlate with other ETS indicators.     

Microdosimetric approach to the problem of lung cancer induced by radon progeny

The increased risk of lung cancer arising from chronic exposure to radon progeny in Czech uranium mines was analyzed on the basis of specific energy distributions for basal and secretory cell nuclei. The distributions were calculated from published results of lung microdosimetry. Whereas classical concepts consider that cell nuclei are hit one or more times by alpha particle tracks, the microdosimetry is able to distinguish glancing (non-lethal, possibly carcinogenic) hits from alpha particle traversals near to nucleus center (which probably inactivate the cell). The simple microdosimetric model differentiates both cases by the quantity termed boundary specific energy. The importance of some confounding factors is examined. Particularly the continuous replacement of bronchial epithelium cells by the new ones is worth considering. Still, the lung cancer frequency seems to be related to the number of sensitive cells with glancing hits. This might be a relevant argument to the toxicity of radon progeny. The central idea of the model, the boundary specific energy, was tested on the basis of radiobiological experiments with isolated cell lines.     

Dietary fats and lung cancer risk among women: the Missouri Women's Health Study (United States)

In a population-based case-control study of women in Missouri (United States), most of whom were smokers, we obtained information on adult diet to evaluate the effects of dietary fats in relation to lung cancer risk. All newly diagnosed, primary lung cancer cases among women 35 to 84 years of age reported to the Missouri Cancer Registry from 1 January 1993 to 31 January 1994 were invited to participate, as were population-based controls. The analysis focused on interviews obtained from 624 controls and 587 cases. In-person interviews were obtained from 99.0 percent of controls and 60.6 percent of cases. Age and energy-adjusted relative risks suggested a direct relation between risk of lung cancer and intake of dietary fats (e.g., total fat, saturated fat) and frequency of meat consumption. After adjusting for confounders, dietary fats were no longer associated with risk, but the adverse effect of frequent consumption of meat persisted. Risk was elevated about 90 percent (95 percent confidence interval = 1.2-3.0) among women in the highest quintile of red meat intake compared with those in the lowest quintile. Risk estimates associated with red meat consumption, however, were dependent on interview status; the effect was restricted to cases whose dietary information was provided by proxy. In summary, after adjusting for potential confounders and removing data obtained from proxy respondents, dietary fats and consumption of red meat were not associated with lung cancer risk among women in Missouri.     

Geography of lung cancer incidence among women and men of Upper Silesia in the years 1986-1990

During a five period (1986-1990) in Katowice province (Upper Silesia) there were 6,140 cases of lung cancer in males and 1,039 females recorded. The standardized (according to age structure of the world population) incidence of lung cancer in both groups, in 93 administrative units (45 cities, 48 communities) significantly vary and are geographically unevenly distributed. The incidence in selected areas in males can be compared with values characterizing regions of the world with highest indices (> 95 per 100,000); whereas in females the incidence of lung cancer is much lower. The prognosis for lung cancer incidence in the Upper Silesia, according to the regression analysis is pessimistic.     

Surgical treatment of primary lung cancer in women

Among 1906 lung carcinoma cases treated in the clinic up to 1975 inclusive, there were 182 women (9.5%). The comparative study of 84 women and 927 men operated upon, proved the operability and resectability in women (46.1% +/- 3.7 and 34.1 +/- 3.5) to be lower than in men (53.8% +/- 1.2 and 46.3% +/- 1.2). Peripheral cancer was found in 28.6% +/- 3.3 of women and in 23.6% +/- 1.0 of men. The main histological form of the tumor in women was glandular carcinoma (45.2% +/- 6.3) and in men squamous cell carcinoma (62.2% +/- 1.7). The lobectomy was the most common of radical operations performed in women (58.1% +/- 6.2); in men it was the pneumectomy (65.1% +/- 1.7). In 6 of 26 women suffering from neoplasm of stage III the vast pneumectomy was carried out; in men this operation constituted 46.1% of all cases of total lung removal. The immediate results in women (complications--14.3% +/- 8.8 and mortality--2.4% +/- 1.7) are better than in men (24.1% +/- 1.4 and 9.3% +/- 1.0). The five-year follow-up showed the survival in women to be 39.1% +/- 10.6 and in men 28.3% +/- 3.0.     

Social support and survival among women with breast cancer

BACKGROUND: Two recently reported randomized trials, one among patients with advanced breast cancer and the other among patients with early stage melanoma, suggested that social support may affect survival favorably. This study assesses relationships of social support indicators with 7-year survival among women diagnosed with localized or regional stage breast cancer. METHODS: All newly diagnosed patients with surgically treated localized or regional disease in seven Quebec City hospitals in 1984 were considered for this analysis. Among 235 eligible patients, 224 (95%) participated in a home interview 3 months after surgery. This interview provided information on the use of confidants in the 3 months after surgery. Data on disease and treatment characteristics were abstracted from patients' medical records. RESULTS: Compared with women who used no confidant in the 3 months after surgery, the hazard ratio for the 7-year period was 0.61 (95% confidence interval [CI], 0.33-1.12) among those who had used at least one confidant, 0.54 (95% CI, 0.28-1.06) in women who used two or more types of confidant, and 0.51 (95% CI, 0.22-1.18) among those whose confidants included either physician or nurse. These results were adjusted for age, presence of invaded axillary lymph nodes, adjuvant radiotherapy, and adjuvant systemic therapy (hormone or chemotherapy). CONCLUSION: These results support the view that social support may be associated with longer survival among women with localized or regional stage breast cancer.     

Breast cancer screening and related attitudes among Filipino-American women

This study assessed mammography screening rates and related attitudes and intervention preferences in Filipino-American women, a group that has been neglected in cancer control research. Face-to-face interviews were conducted in English and Tagalog with a convenience sample of 218 Filipino women 50 years and older residing in Los Angeles. Sixty-six % had ever had a screening mammogram, 42% had had one in the past 12 months, and 54% in the past 2 years. These rates are about 20% lower than those found among African-American and white women in the 1994 California Behavioral Risk Factor Survey. Women who had received a doctor's recommendation to obtain a mammogram, women stating that they were very likely to obtain a mammogram if a physician recommended it, and women who felt very comfortable requesting a mammogram from a physician were more likely to have been screened. Women who had friends and relatives who had obtained mammograms those stating that their friends and relatives would be very supportive of their getting a mammogram, and those who felt that it was very worthwhile to obtain a mammogram were also more likely to have been screened. The following variables were negatively related to the outcome: concern over cost, the attitude that mammograms are only needed in the presence of symptoms, perceived inconvenience of taking the time and difficulties getting to the mammography facility, and embarrassment. Implications for interventions to increase breast cancer screening are discussed.     

Breastfeeding experience and breast cancer risk among postmenopausal women

A method of automated detection of onset and termination of rhythmic muscle activity in electromyograms (EMGs) is presented. A threshold level in the EMG is computed, such that amplitudes in the EMG signal exceeding this level indicate muscle activity. The threshold level is determined using a statistical criterion based on the amplitude distribution of the entire EMG signal. The working of the method is illustrated with EMG signals recorded from chewing muscles. EMG signals with a good as well as a worse signal-to-noise ratio are presented. The method can be used for any EMG signal containing cyclic bursts of activity and thus may be applied in studies on rhythmic movements, such as chewing, walking and breathing. An automated method of EMG burst detection has the advantage that large amounts of EMG data can be easily and objectively processed.     

Breast cancer among women exposed to polybrominated biphenyls

We conducted a nested case-control study with 1,925 women enrolled in a polybrominated biphenyl (PBB) registry to examine the association between breast cancer and serum PBBs. Twenty women who developed breast cancer were matched to 290 control subjects on sex, race, and age. Women with serum PBB levels of 2.0-3.0 parts per billion (ppb) [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 0.9-13] or 4.0 ppb or greater (OR = 3.1; 95% CI = 0.8-12) had a higher estimated risk for breast cancer than women with less than 2.0 ppb. The odds ratios were unchanged when available breast cancer risk factors were included in the analysis.