Asbestos and colon cancer: a weight-of-the-evidence review.

What is the evidence that exposure to asbestos causes colon cancer? This weight-of-evidence review considers epidemiologic evidence from cohort studies of asbestos-exposed workers, case-control studies of colon cancer, animal bioassays, and other corroborative evidence. The major evidence for a causal association at high exposure is a combined colorectal standardized mortality ratio (SMR) of 1.5 for asbestos cohorts where the lung cancer SMR was greater than twofold. However, misdiagnosis may spuriously elevate the SMR. The strongest evidence against a causal association between colon cancer and asbestos exposure is the lack of an exposure-response gradient in asbestos cohorts where trends for lung cancer are observed. Population-based case-control studies of colon cancer do not show any consistent risk associated with asbestos exposure. Long-term ingestion studies show no evidence of an increased incidence of colon cancer in animals by this route of exposure and do not provide biological plausibility for a causal association between asbestos exposure and colon cancer.

PM2.5 and mortality in long-term prospective cohort studies: cause-effect or statistical associations?

Concentrations of ambient PM2.5 (particulate matter <2.5 microm in aerodynamic diameter) were associated with increased mortality in two prospective cohort studies. In this paper, I assess whether the weight of the evidence supports a causal association. I assumed the study population in each city to have the same exposure; therefore, these are ecologic studies because exposure is at the group level. Health outcome and confounding data are at the individual level. Ambient PM concentrations are inadequate surrogates for personal exposure because they are at the group level and comprise only a small proportion of personal exposure, they change over time, and they constitute only a small proportion of a life span. The strength of association and exposure-response relationships cannot be determined because the ecologic group-level risks of PM2.5 are overestimated 150- to 300-fold based on an analogy with individual-level exposure to inhaled cigarette smoke. Risk estimates may also be high because of confounding from factors such as physical activity and lung function. The evidence is not coherent because the stronger associations are expected to be with morbidity, but instead are with mortality. For example, PM2.5 was associated with mortality but not with measurable reductions in lung function. Biological plausibility is lacking because lifetime exposure of rats to combustion products at concentrations two to three orders of magnitude higher than air pollution levels cause lung overloading but no consistent reduction in survival. Criteria for quantitative risk assessment are not met so the data are not useful for setting air quality standards. The weight of evidence suggests there is no substantive basis for concluding that a cause-effect relationship exists between long-term ambient PM2.5 and increased mortality.

Health and respirable particulate (PM10) air pollution: a causal or statistical association?

Numerous studies have reported weak but statistically significant acute health effects of particulate air pollution. The associations are observed at levels below the current U.S. standard of 150 micrograms/m3 (24 hr). Health effects include acute increased mortality from cardiopulmonary conditions and acute morbidity such as hospital admissions for related diseases. We reviewed recent epidemiology studies to evaluate whether criteria for causality are met, and we conclude that they are not. The weak associations are as likely to be due to confounding by weather, copollutants, or exposure misclassification as by ambient particulate matter (PM). The results from the same metropolitan areas are inconsistent, and PM explains such a small amount of the variability in mortality/morbidity that the association has little practical significance. Finally, experimental chamber studies of susceptible individuals exposed to PM concentrations well above 150 micrograms/m3 provide no evidence to support the morbidity/mortality findings. None of the criteria for establishing causality of the PM/mortality hypothesis are clearly met at ambient concentrations common in many U.S. cities.

A nested case-control study of kidney cancer among refinery/petrochemical workers.

A nested case-control study was designed to evaluate whether a nearly twofold excess of kidney cancer among workers at a refinery/petrochemical plant was associated with cumulative exposure to C2-C5 saturated, C2-C5 unsaturated, C6-C10 aliphatic saturated, C6-C10 aliphatic unsaturated, and C6-C10 aromatic process streams. Nonoccupational risk factors were body mass index (BMI), blood pressure (both measured at about age 28), and smoking. There was no significant association with cumulative exposure or tenure as estimated by conditional logistic regression and adjusted for nonoccupational risk factors. Categorical analysis showed increased odds ratios only in the second (low) and fourth (high) quartiles compared to the first quartile reference group of lowest exposed workers, and a three-quarter-fold increased odds ratio for > 32 years' tenure compared to the < 25-year reference group. The number of cases was small with wide confidence intervals around estimate of risk, so the possibility of an exposure-response trend cannot be ruled out. Multivariate analysis identified overweight (high BMI; p < 0.01) as the most important risk factor in this data set, followed by tenure and increased blood pressure. There was a weak association with current smoking, but not with pack-years smoked. The risk of kidney cancer for a nonsmoker with normal blood pressure but 25% overweight was increased about 2.6-fold (95% CI = 1.2-5.4). The risk of kidney cancer for a nonsmoker of normal weight with high blood pressure (e.g., 150/110), was increased about 4.5 (95% CI, 0.8-26).

Mortality among three refinery/petrochemical plant cohorts. I. 1970 to 1982 active/terminated workers.

This study updates mortality rates for 19,075 active and terminated workers at three refinery/petrochemical plants. Mortality rates of the workers were compared with both national and state rates. The results indicated deficits of deaths for all causes, all malignant neoplasms, and respiratory and prostate cancer. The noteworthy finding was a statistically significant increase in leukemia among Louisiana male subjects (standardized mortality ratio [SMR], 181; 95% confidence interval [CI], 122 to 259), which showed suggestive trends of increasing SMRs with increasing tenure. This excess was largely due to increased chronic lymphocytic leukemia (SMR, 351; 95% CI, 168 to 645). The rate of kidney cancer remained elevated among Louisiana male subjects, but this finding was no longer significant, and there were no patterns in SMRs by tenure and latency. Mesothelioma was increased at the Louisiana (SMR, 198; 95% CI, 72 to 430) and Texas (SMR, 246; 95% CI, 99 to 507) locations. The leukemia findings have prompted a study of leukemia incidence at the Louisiana location.

Mortality among three refinery/petrochemical plant cohorts. II. Retirees.

This study updates mortality data for 6238 retirees from three refinery/petrochemical plants. Almost 90% of the cohort was deceased. Deaths from all causes (standardized mortality ratio, 104; 95% confidence interval, 102 to 107) and all cancers (standardized mortality ratio, 109; 95% confidence interval, 102 to 116) were elevated. Increased deaths due to kidney cancer, mesothelioma, and the category of other lymphohemopoietic cancers also were observed. The rate of leukemia was not increased. There was little internal or external consistency to support an occupational relationship for kidney cancer, but findings for mesothelioma and other lymphohemopoietic cancers are consistent with reports for other petroleum cohorts. Analyses by age indicated significantly higher all-cause mortality rates among persons retiring before age 65. The results suggest that continued surveillance of mesothelioma and lymphohemopoietic cancer malignancies in younger workers with more contemporary exposures may be warranted. Furthermore, age at retirement should be considered when analyzing occupational cohorts.

Silica, silicosis, and lung cancer: a response to a recent working group report.

The relationship between crystalline silica and lung cancer has been the subject of many recent publications, conferences, and regulatory considerations. An influential, international body has determined that there was sufficient evidence to conclude that quartz and cristobalite are carcinogenic in humans. The present authors believe that the results of these studies are inconsistent and, when positive, only weakly positive. Other, methodologically strong, negative studies have not been considered, and several studies viewed as providing evidence supporting the carcinogenicity of silica have significant methodological weaknesses. Silica is not directly genotoxic and is a pulmonary carcinogen only in the rat, a species that seems to be inappropriate for assessing particulate carcinogenesis in humans. Data on humans demonstrate a lack of association between lung cancer and exposure to crystalline silica. Exposure-response relationships have generally not been found. Studies in which silicotic patients were not identified from compensation registries and in which enumeration was complete did not support a causal association between silicosis and lung cancer, which further argues against the carcinogenicity of crystalline silica.

Lung cancer, stomach cancer, and smoking status among coal miners. A preliminary test of a hypothesis.

This paper presents an empirical test of the hypothesis of Meyer et al, who propose inhaled carcinogens to be a risk for both stomach and lung cancer, stomach cancer occurring in persons with nonimpaired lungs and lung cancer occurring in persons with impaired lungs. Based upon a case-referent study comparing 46 white male coal miners who died from stomach cancer in the United States with age-matched miners who died from lung cancer and with reference miners who died from other cancers or from noncancer, nonaccident causes, the present study failed to confirm the Meyer hypothesis. The data suggest a reverse relationship than that postulated, namely, that airway obstruction may be a precondition for stomach cancer and normal pulmonary function a precondition for lung cancer. Different dust agents were found to be involved with cancers at the different sites. For coal miners with airway obstruction, greater years of coal mine dust exposure were found to pose a slightly elevated stomach cancer risk (odds ratio 3.64, not significant), while, for miners with normal ventilatory function, cigarette smoking posed a disproportionately elevated lung cancer risk (odds ratio 7.00, not significant).

Exposure-response of asphalt fumes with changes in pulmonary function and symptoms.

OBJECTIVES: This study examines possible associations between asphalt fumes and workshift changes in lung function and symptoms among 170 workers exposed to asphalt fumes. METHODS: The workers were from 5 segments of the asphalt industry, and most of them participated for 2 consecutive workdays. The primary response variables were changes in lung function (measured at the beginning and end of the shift) and incidence of symptoms (measured before, 3 times during, and at the end of the shift). Exposure was estimated from breathing-zone samples of total particulate (TP), respirable particulate (RP), the benzene-soluble fraction of the TP (BSF), volatile hydrocarbons collected on a charcoal tube (VHC), nitrogen dioxide, sulfur dioxide, formaldehyde, carbon monoxide, and hydrogen sulfide. Ozone and wet bulb/dry bulb temperature, as a measure of heat stress, were measured as area samples. In addition, daily cigarette smoking was determined by questionnaire. The exposure-response associations were assessed by both parametric and nonparametric statistical techniques. RESULTS: Overall, no consistent association was observed between an acute reduction in lung function or the incidence of symptoms and exposure to asphalt fumes. Concentrations in the neighborhood of the maximum levels constitute no-observed adverse effect levels: TP (<1.5 mg/m3 to maximum 6.2 mg/m3), RP (<0.6 mg/m3 to maximum 1.4 mg/m3), BSF (<0.6 mg/m3 to maximum 1.3 mg/m3), VHC (<8 mg/m3 to maximum 19.8 mg/m3). There were no exposure-response trends with ozone, heat stress, cigarettes smoked, or length of workday.

The role of the lung in stomach carcinogenesis: a revision of the Meyer hypothesis.

Meyer et al. present an hypothesis postulating an essential opposition between lung cancer and stomach cancer based upon the interaction between cigarette smoking, respiratory impairment, and exposure to airborne carcinogens. Their theory is that respiratory impairment serves as a gate to determine whether carcinogenic airborne particulate is retained in the lungs to produce lung cancer or is cleared and swallowed to produce stomach cancer. This paper examines the foundations of the Meyer hypothesis, identifies particle deposition patterns as a crucial Meyer omission, and presents a reformulated theory based upon both particle deposition and particle retention.

Comparison of ambient PM risk with risks estimated from PM components of smoking and occupational exposures.

Air pollution studies are based on individual-level health response data and group-level exposure data. Therefore, exposure misclassification occurs, and the results may be biased to an unknown magnitude and direction. Testing the validity of such associations requires a study design using individual-level data for both exposure and response. One can test the plausibility of group-level PM risk estimates by comparing them to individual-level estimates of risk from constituents of ambient air. The twofold purpose of this review is to consider the internal consistency of risks estimated from the three major PM cohort studies and to determine individual-level mortality risks associated with ambient concentrations of tobacco smoke and occupational exposures and compare them with risks associated with ambient PM. The paper demonstrates the risks are not consistent within and between the PM cohort studies. Higher ambient concentration risks (ACRs) from the ambient PM cohort studies are not coherent with ACRs derived from individual-level smoking and occupational risks for total, cardiopulmonary, and lung cancer mortality. Individual-level studies suggest increased risk of mortality cannot be measured with reliability at concentrations found in ambient air.

Asbestos, asbestosis, and lung cancer: a critical assessment of the epidemiological evidence.

The question of whether lung cancer can be attributed to asbestos exposure in the absence of asbestosis remains controversial. Nine key epidemiological papers are reviewed in a point/counterpoint format, giving the main strengths and limitations of the evidence presented. Of the nine papers, two concluded that asbestosis was necessary and seven that it was not. However, the study design, nature and circumstances of exposure and method of analysis of the studies differed considerably, and none was considered definitive. It is concluded that, because of the relative insensitivity of chest radiography and the uncertain specificity of findings from histological examinations or computed tomography, it is unlikely that epidemiology alone can put either the strict scientific or practical medicolegal questions beyond doubt. It is probable that the issue may depend critically on asbestos fibre type, an aspect not so far addressed.

Low-level hydrocarbon solvent exposure and neurobehavioural effects.

Studies of workers exposed to hydrocarbon solvents are reviewed in order to address the question, 'Does long-term human exposure to hydrocarbon solvents at concentrations around occupational exposure limits result in clinically important neurobehavioural effects?' Studies selected evaluated exposure-response (E-R) trends with some control of potential confounders. Tests of neurobehavioural performance were classified into specific functional categories, within those of cognitive, psychomotor and sensory functions to increase specificity and power to detect patterns of effect. The weight-of-evidence was evaluated with respect to criteria for determining causality. The temporality criterion was met as latency was adequate for the occurrence of chronic effects. There were few significant associations, and when present, were consistently weak even in the most-exposed workers. Exposure response showed no consistent or significant pattern for any tests of functional mortality. The weight of evidence suggests that exposure to hydrocarbon solvents at current limits does not appear to cause adverse neurobehavioural effects.

A nested case control study of lung cancer among New York talc workers.

This nested case control study assessed the relationship of lung cancer and time exposed to talc, while controlling for smoking, other talc exposures, and nontalc exposures. There were 22 lung cancer cases (91% smokers and 9% former smokers) and 66 controls (27% nonsmokers, 9% former smokers, and 64% smokers). Smokers were at sixfold increased risk compared to nonsmokers and ex-smokers. When stratified by smoking status, risk of lung cancer decreased with talc tenure and remained negative when excluding cases with < 20 years' latency and short-term workers. These data suggest that nontalc exposures are not confounding risk factors while smoking is, and that temporal and exposure-response relationships are consistent with a smoking etiology but not an occupational etiology for lung cancer.

Respiratory effects of diesel exhaust in salt miners.

The respiratory health of 259 white males working at 5 salt (NaCl) mines was assessed by questionnaire, chest radiographs, and air and He-O2 spirometry. Response variables were symptoms, pneumoconiosis, and spirometry. Predictor variables included age, height, smoking, mine, and tenure in diesel-exposed jobs. The purpose was to assess the association of response measures of respiratory health with exposure to diesel exhaust. There were only 2 cases of Grade 1 pneumoconiosis, so no further analysis was done. Comparisons within the study population showed a statistically significant dose-related association of phlegm and diesel exposure. There was a nonsignificant trend for cough and dyspnea, and no association with spirometry. Age- and smoking-adjusted rates of cough, phlegm, and dyspnea were 145, 159, and 93% of an external comparison population. Percent predicted flow rates showed statistically significant reductions, but the reductions were small and there were no dose-response relations. Percent predicted FEV1 and FVC were about 96% of predicted.