Brain cancer and occupational exposure to lead

A recent report in the literature suggested a link between occupational exposure to lead and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992. Brain cancer risk increased by probability of exposure to lead among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lead (odds ratio = 2.1; 95% confidence interval, 1.1-4.0). Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined). Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis.     

A novel approach to data collection in a case-control study of cancer and occupational exposures

BACKGROUND: In community and hospital-based case-control studies, the occupational data collected in interviews are usually limited to responses to general questions asked of all study subjects. A procedure is described in which more detailed information can be collected in an efficient, standardized and systematic way. METHODS: A generic work history is initially collected from all subjects using a computer-assisted interview. The work history includes job title, type of business, job activities, materials and chemicals, and tools and equipment used. After responses are entered into the computer by the interviewer, the computer searches a synonym file to identify possible job-specific modules relevant to the reported job. The modules are detailed questionnaires that address specific jobs administered after obtaining the generic work history. The modules are used to ask questions about the work environment; sources of exposure; factors affecting the movement of the agent from the source to the subject, such as local exhaust ventilation; and individual and job characteristics. After the interview is completed, the work history and responses to the modules are sent electronically to an industrial hygienist who reviews the information using a custom-designed software package. Where ambiguities or contradictions occur in information reported by the respondent, or for jobs for which no module had been developed, the industrial hygienist generates up to 10 additional questions per job. These questions are sent back to the interviewer for administration of a short, second interview. CONCLUSIONS: These procedures, which are being successfully implemented in an on-going case-control study of brain tumours, should improve disease risk estimates over those derived from more traditional approaches to exposure assessment.     

Anthropometric and other risk factors for ovarian cancer in a case-control study

Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case-control study was conducted to assess some environmental and other risk factors for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P = 0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P < 0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P < 0.01) and the number of live births (P < 0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.     

Associations between several sites of cancer and occupational exposure to benzene, toluene, xylene, and styrene: results of a case-control study in Montreal

Since the first issue in 1977. Disasters has been one of the pre-eminent refereed journals on the study and reporting of disasters. This article reviews 703 articles and reports in the journal through 1996 to provide a snapshot of the nature of the journal throughout 20 years of publication. The results indicate the most common contributions: first, were research articles by authors from the North Atlantic; second, most often dealt with natural disaster relief or impact; and third, most frequently focused on Africa. These generalisations, however, do not reflect attention paid to food-related and political disasters and greatly understate the broad diversity of material presented in the journal. To improve the topical and geographic coverage of Disasters probably requires a proactive effort to close gaps in the journal's coverage of disasters.     

Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden

BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.     

Renal cell cancer correlated with occupational exposure to trichloroethene

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).     

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.     

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.     

Is testicular cancer an occupational disease? A case-control study of Royal Naval personnel

Testicular cancer is the commonest malignancy arising in men actively serving in the Royal Navy. This study, which includes a literature review of the aetiology of the disease, is designed to determine the relative risk of developing testicular cancer in various occupational groups within the Service by means of a Case-Control study. All cases of testicular cancer occurring in serving personnel between 1976 and June 1994, inclusive, were identified. One hundred and ten cases were found. Four randomly selected controls were matched on the basis of date of birth and length of service to each case. Results reveal statistically significant increased Odds Ratios for members of the Fleet Air Arm (OR = 1.90 95% CI: 1.04-3.48). Air Engineers (OR = 2.32 95% CI: 1.20-4.48) and the Aircraft Handling sub-specialty (OR = 7.31 95% CI: 1.81-29.53). It is speculated that exposure to glycol ethers in aviation fuel may be the causative mechanism. No associations were found in relation to ionising radiation exposures or length of time served in nuclear submarines.     

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.     

Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark

To explore prenatal risk factors that are common to testicular cancer and cryptorchidism, two parallel case-control studies were conducted in Denmark. Information about characteristics of the mother, the pregnancy, and the birth were obtained from the mothers of cases and controls, using a mailed self-administered questionnaire. A maternal age above 30 years was associated with odds ratios (OR) of 1.9 (95 percent confidence interval [CI] = 1.2-3.0) for cryptorchidism and 2.0 (CI = 1.2-3.6) for testicular seminoma; the latter effect was particularly high when the boy was the first child of the mother (OR = 4.1, CI = 1.1-14.6). Birthweights below 3,000 g or above 4,000 g were associated with increased risks of testicular cancer, with ORs up to 2.6 (CI = 1.1-5.9) for birthweight below 2,500 g. For cryptorchidism, there was a monotonous trend in the OR from 0.4 in birthweights above 4,500 g to 2.3 in birthweights below 2,500 g. The association between cryptorchidism and testicular cancer was not attenuated by adjustment for maternal age and birthweight, indicating that all three variables are independent risk factors for testicular cancer. With the exception of high maternal age, which consistently is associated more strongly with seminoma than with non-seminoma, it remains most likely that seminoma and non-seminoma have similar causes.     

Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany

The association between childhood leukaemia and exposure to pesticides was examined in a population-based case-control study conducted in Lower Saxony, Northern Germany. Between July 1988 and June 1992, 219 newly diagnosed cases were identified, of whom 173 participated in the study. Two sex- and age-matched control groups were recruited: local controls from the same communities as the newly diagnosed cases of leukaemia and state controls from other randomly selected communities in Lower Saxony. An additional study group consisted of 175 cases of solid tumours. When the leukaemia cases were compared with the local controls, positive associations with parental occupational exposure, particularly agriculture-related exposure, were observed, which were statistically non-significant. A significant association was found for pesticide use in gardens (odds ratio = 2.52, 95% confidence interval: 1.0-6.1). No positive associations were seen when the leukaemia cases were compared to the state controls, but this finding could be explained by a higher proportion of state controls living in rural areas. In communities with a significantly elevated standardised incidence ratio of childhood leukaemia over the last decade (1984-1993), the prevalence of pesticide use in the garden was 21%, compared with the 10% in other communities. None of the examined risk factors were more common among cases of solid tumours. Our findings add some evidence to the hypothesis that pesticides are a risk factor for childhood leukaemia, and there are good reasons to consider abundant pesticide use in rural areas as a possible cause for clustering of childhood leukaemia.     

A case-control study of prostate cancer

We present tyndallometry as a method for investigation of subclinical changes in anterior-chamber flare in patients with risk factors regarding anterior-segment ischemia after squint surgery. The cases of six adult patients who underwent surgery on the vertical recti and who had additional risk either because of dysthyroid orbitopathy or because of transpositions carried out on the recti are presented. In one case a transient subclinical increase in the flare value was observed. This noninvasive method seems suitable for the provision of further information on the pathophysiology of anterior-segment ischemia and for monitoring of patients at special risk postoperatively such that early treatment can be started if necessary. Additionally, early detection of nonischemic intraocular inflammation in the postoperative course is rendered possible by this examination.     

Pulmonary fibrosis and occupational exposure to aluminum

Many reports of respiratory disease attributable to aluminum exposure have appeared in the European medical literature during the last 50 years. Great Britain and Germany are two major industrialized nations that acknowledge a causal relationship between occupational exposure to aluminum and respiratory impairment. For factory workers in these countries, pulmonary disease attributed to respirable aluminum particulates is compensated as a workplace disability. In North America, however, there is a lack of consensus regarding the pathogenicity of aluminum fumes and dust to the worker. This view may be based on a difference in the types of industrial usage, the updated methods of aluminum processing in this country, or the benefits of a modern workplace. It has also been proposed that the development of aluminum-induced pulmonary disease may depend on a particular host factor that has not yet been identified. We describe a patient whom we believe developed severe respiratory compromise and irreversible pulmonary fibrosis from a lifetime of industrial aluminum exposure.     

Differential exposure misclassification in case-control studies of environmental tobacco smoke and lung cancer

We review some of the literature on the effects of exposure misclassification on the statistical analysis of case-control studies. In particular, we focus on evidence for exposure misclassification which may be different for cases and controls in studies of environmental tobacco smoke (ETS). For example, such misclassification could induce relative risk estimates below unity for low exposure which appears to be the case in U.S. lung cancer and ETS studies. We describe procedures for systematically examining the sensitivity of dose-response statistics on exposure misclassification. The procedures demonstrate how p-values for the null hypothesis of no dose-response trend could be adjusted to account for exposure misclassification. The adjustment procedures were applied to an example based on a recently published large study of ETS and lung cancer in which a p-value for trend was reported as 0.03. In this example it is seen that modest differential exposure misclassification can induce substantial increases in the actual p-value, changing what appears to be statistically significant to decidedly nonsignificant.     

Brain stem evoked potentials and visual evoked potentials in relation to the length of occupational exposure to low levels of toluene

In 49 printing-press workers occupationally exposed to toluene for approximately 21.6 years, the values of BEAP and VEP parameters were examined in relation to the length of exposure. With the exception of P2 wave, there was a significant increase in the latencies of all the BEAP waves examined as well as in the interpeak latency (IPL) P3-P4, whereas IPL P4-P5 decreased significantly with the length of exposure. The amplitude of all the VEP examined decreased significantly with the length of exposure. Toluene exposure was evaluated by measuring the concentration of toluene in peripheral blood and of hippuric acid in urine on Wednesday morning prior to the workshift, and of hippuric acid in urine after the workshift on the same day. According to the average concentration of hippuric acid in urine after the workshift, the levels of toluene exposure were estimated to range from 40-60 ppm. Evoked potentials were determined on Mondays 10-12 hours after a nonworking weekend.     

A case-control study of fatty liver disease and organic solvent exposure

BACKGROUND: Clinical experience of cases of fatty liver disease (FLD) with exposure to organic solvents suggested a possible risk. METHODS: Thirty male cases of FLD, ages 20-59 years, with biopsy records at departments of pathology in southeast Sweden were compared to 120 male controls randomly drawn from the study area population. Questionnaire information was obtained about job titles and specific occupational exposures; exposure level categories were then assessed blindly for both cases and controls. Medical records for cases were scrutinized to elucidate possible confounding and/or interacting effects from alcohol, the use of drugs, and other diseases. RESULTS: Moderately intense and mixed solvent exposure for more than 1 year within the last 15 years prior to diagnosis resulted in an age-adjusted Mantel-Haenszel odds ratio of 4.3 (95% confidence interval (CI), 1.2-15); for intense exposure, the odds ratio was 7.7 (95% CI 1.7-48). Confounding from alcohol, use of drugs, other diseases, and overweight could be ruled out with reasonable confidence. CONCLUSIONS: This study indicates that occupational exposure to organic solvents may play a role in the development of FLD, as indicated earlier in case reports and in one small case-control study.