Assessment of lifetime exposure to trihalomethanes through different routes.

OBJECTIVES: To evaluate lifetime exposure to trihalomethanes (THM) through ingestion, inhalation, and dermal absorption in a hospital based case-control study of bladder cancer conducted between 1998 and 2001 in five areas of Spain. The study base was comprised of subjects living in the catchment areas of the participating hospitals. METHODS: Individual information on water related habits was obtained from personal interviews of 1219 cases and 1271 controls: residential and occupational history, drinking water source at each residence and job, amount of water consumption, frequency and duration of showering, bathing, and swimming pool attendance. THM levels, water source history, and year when chlorination started in study areas were ascertained through measurements in drinking water samples and questionnaires to water companies and local authorities. Estimates of THM levels covered 79% of the subjects' person-years of exposure. RESULTS: Current and historical average THM levels in water were correlated. Control subjects reported that drinking water source in the last residence was municipal for 63%, bottled for 22%, private well for 2%, and other sources for 13%. For the time window between age 15 and the time of interview, average residential THM level was 32.2 mug/l. THM exposure through ingestion was 23.7 mug/day on average, and was correlated with the ingestion THM level in the workplace. Overall, 79% usually took showers, 16% usually took baths, and 13% had ever attended a swimming pool. Between 21% and 45% of controls unexposed to THM through ingestion were evaluated as moderately or highly exposed through showering or bathing, and 5-10% were exposed through swimming in pools. CONCLUSION: The importance of evaluating different routes is underscored by findings from experimental studies showing substantial differences in THM uptake and internal distribution by route.

Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study.

OBJECTIVES: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure-response data. We have conducted a pooled exposure-response analysis of 10 silica-exposed cohorts to investigate lung cancer. METHODS: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1,072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. RESULTS: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0. 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1-1.7%, above background risks of 3-6%. CONCLUSIONS: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies.

Excess incidence of squamous cell esophageal cancer among US Black men: role of social class and other risk factors.

Data from a population-based case-control study were used to evaluate the relation between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and low income contribute to the higher incidence among Black men than among White men in the United States. A total of 347 male cases (119 White, 228 Black) and 1,354 male controls (743 White, 611 Black) were selected from three US geographic areas (Atlanta, Georgia, Detroit, Michigan, and New Jersey). Cases were residents of the study areas aged 30-79 years who had been diagnosed with histologically confirmed esophageal cancer between 1986 and 1989. The adjusted odds ratios for subjects with annual incomes less than $10,000 versus incomes of $25,000 or more were 4.3 (95% confidence interval: 2.1, 8.7) for Whites and 8.0 (95% confidence interval: 4.3, 15.0) for Blacks. The combination of all four major risk factors-low income, moderate/heavy alcohol intake, tobacco use, and infrequent consumption of raw fruits and vegetables-accounted for almost all of the squamous cell esophageal cancers in Whites (98%) and Blacks (99%) and for 99% of the excess incidence among Black men. Thus, lifestyle modifications, especially a lowered intake of alcoholic beverages, would markedly decrease the incidence of squamous cell esophageal cancer in both racial groups and would narrow the racial disparity in risk. Further studies on the determinants of social class may help to identify a new set of exposures for this tumor that are amenable to intervention.

The excess incidence of squamous cell esophageal cancer among us black men. Role of social class and other risk factors.

PURPOSE: To investigate the relationship between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and social class contribute to the five-fold higher incidence among black than white men in the United States.METHODS: Interviews were conducted with 347 incident cases of squamous cell esophageal cancer (119 white males and 228 black males) and 1354 population-based controls (743 white males and 611 black males) from Atlanta, Detroit, and New Jersey. Risks were estimated using unconditional logistic regression controlling for potential confounders.RESULTS: Elevated risks of squamous cell esophageal cancer were associated with indicators of low social class, especially low annual income. The adjusted odds ratios (ORs) for subjects with incomes < $10,000 versus incomes of $25,000 or more were 4.3 (95% CI = 2.1-8.7) for whites and 8.0 (95% CI = 4.3-15.0) for blacks. The combination of all four major risk factors: annual income less than $25,000, moderate/heavy use of alcohol, use of tobacco for six months or longer, and consumption of less than 2.5 servings of raw fruits and vegetables per day accounted for almost all of the squamous cell esophageal cancers in whites (98%) and blacks (99%), and for 99% of the excess incidence among black men.CONCLUSIONS: Lifestyle modifications, especially a lower intake of alcoholic beverages, would markedly decrease the incidence of this cancer in both races and narrow the racial disparity in risk. Further studies into the determinants of social class may help identify a new set of exposures for this tumor that are amendable to intervention.

Socioeconomic status and multiple myeloma among US blacks and whites.

OBJECTIVES: This study examined the relation between socioeconomic status (SES) and risk of multiple myeloma among Blacks and Whites in the United States. METHODS: This population-based case-control study included 573 cases (206 Blacks and 367 Whites) with new diagnoses of multiple myeloma identified between August 1, 1986, and April 30, 1989, and 2131 controls (967 Blacks and 1164 Whites) from 3 US geographic areas. Information on occupation, income, and education was obtained by personal interview. RESULTS: Inverse gradients in risk were associated with occupation-based SES, income, and education. Risks were significantly elevated for subjects in the lowest categories of occupation-based SES (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.16, 2.53), education (OR = 1.36, 95% CI = 1.06, 1.75), and income (OR = 1.43, 95% CI = 1.05, 1.93). Occupation-based low SES accounted for 37% of multiple myeloma in Blacks and 17% in Whites, as well as 49% of the excess incidence in Blacks. Low education and low income accounted for 17% and 28% of the excess incidence in Blacks, respectively. CONCLUSIONS: Our results indicate that the measured SES-related factors account for a substantial amount of the Black-White differential in multiple myeloma incidence.

Exposure assessment for a study of workers exposed to acrylonitrile.

Procedures used to develop estimates of exposure to acrylonitrile for a cohort study (>25000 workers in 8 monomer, fiber, and resin companies from 1952 to 1983) are presented. Visits to the companies were made, interviews of workers were conducted, historical records were made, and measurements were taken. On the basis of similar tasks, locations, other exposures, and a similar distribution of exposures to acrylonitrile, 3600 exposure groups were formed. Special procedures were used to reduce the misclassification of workers performing tasks that varied in time but that were inadequately reflected in the job title. A software program organized and retained all exposure information on each exposure group. Quantitative estimates of acrylonitrile exposure were developed using a hierarchical approach in a software program that documented the derivation of each estimate and facilitated data review. Two of the estimation methods were evaluated in a comparison with measurement data.

Occupational risk factors for cancer of the central nervous system: a case-control study on death certificates from 24 U.S. states.

The risk of cancer of the central nervous system (CNS) by industry and occupation was investigated with a case-control analysis of the death certificates of 28,416 cases and 113,664 controls, selected from over 4.5 million deaths in 24 U.S. states between 1984 and 1992. Industries showing consistent increases in risk by gender and race included textile mills, paper mills, printing and publishing industries, petroleum refining, motor vehicles manufacturing, telephone and electric utilities, department stores, health care services, elementary and secondary schools, and colleges and universities. CNS cancer risk was increased for administrators in education and related fields, secondary school teachers, and other education- and health-related occupations. The application of job-exposure matrices to the industry/occupation combinations revealed a modest increase in risk for potential contact with the public at work and exposure to solvents. Occupational exposure to electromagnetic fields (EMF) was not associated with CNS cancer, although an association was observed with a few EMF-related occupations and industries. Agricultural exposures were associated with significant risk increases among white women and white men. Further work is required to investigate in more detail specific occupational exposures or possible confounders responsible for the observed associations.

Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey.

Effects of tobacco smoking and alcohol use on risks of cancers of the larynx and lung have been evaluated extensively in industrialized countries. Few studies on the effect of these risk factors have been reported from developing countries. We conducted a case-control study to evaluate risks of laryngeal and lung cancers in men by subsite and cell type in relation to smoking and alcohol drinking in Turkey, a country where smoking and alcohol consumption patterns are different from those in industrialized countries. We identified 832 laryngeal and 1,210 lung cancer cases and 829 controls with information on smoking and alcohol use (amount and duration) and histologic cell type from an oncology treatment center of a Social Security Agency hospital in Istanbul, Turkey, admitted between 1979 and 1984. Both laryngeal and lung cancer showed significant associations with smoking and alcohol drinking, but no monotonic dose-response was obtained for alcohol drinking. Among smokers, the highest risks were observed in the supraglottis region of the larynx (odds ratio [OR] = 4.1) after adjustment for age and alcohol use. Among alcohol drinkers, the highest risks were observed in the glottis region of the larynx (OR = 1.7) after adjustment for age and smoking. In the analysis by the cell type of lung cancer among ever-smokers, small cell type showed the highest risk (OR = 5.4), while it showed no association with alcohol drinking. Cumulative cigarette use (pack-years) and number of cigarettes per day showed stronger associations than years smoked for both cancer sites. The relative risks of joint exposure to smoking and alcohol were 12.2 for laryngeal cancer and 14.1 for lung cancer among heavy smokers and heavy alcohol drinkers. This study provides epidemiologic evidence from Turkey that smoking and alcohol use are associated with risks of cancers of the larynx and lung.

Validation of benzene exposure assessment.

We conducted a methodologic study to validate a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work-unit/job-title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures occurred in the rubber industry (30.7 ppm), particularly for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning (hematotoxicity) and benzene exposure was evaluated (412 cases and 614,509 person-years) to validate the exposure-assessment method. Relative risks of benzene hematotoxicity increased very sharply with increasing estimated intensity of benzene exposure. Odds ratios were 2.2 (95% CI: 1.7-2.9), 4.7 (95% CI: 3.4-6.5), and 7.2 (95% CI: 5.3-9.8) for the intensity levels of less than 5 ppm, 5-19 ppm, 20-39 ppm, and 40 and more ppm, respectively. This sharp trend between benzene hematotoxicity and estimated exposure to benzene indicated that the exposure-estimation method used in this cancer epidemiology study is reliable.

Indirect validation of benzene exposure assessment by association with benzene poisoning.

We present a validation study of a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work unit/job title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures were observed for the rubber industry (30.7 ppm) and for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning and benzene exposure was evaluated to validate the assessment method that we used in the cohort study. Our confidence in the assessment method is supported by the observation of a strong positive trend between benzene poisoning and various measures, especially recent intensity of exposure to benzene.

Cohort study among workers exposed to benzene in China: II. Exposure assessment.

This report describes a retrospective exposure assessment method used in a follow-up mortality study of workers exposed to benzene. The approach quantified historical exposure to benzene in a multi-industry, multicenter cohort, involving 672 factories in 12 cities in China. Historical exposure data were collected to obtain exposure information related to 1,427 work units (departments) and 3,179 unique job titles from benzene-producing or -using factories in which written records and other data sources were evaluated. The basic unit for exposure assessment was a factory/work unit/job title combination which was considered separately during each of seven calendar-year time periods between 1949 and 1987 for a total of 18,435 exposure assignments. Historical information collected to estimate exposure included benzene monitoring data; lists of raw materials and factory products, and the percentage of benzene in each; the total amount and dates of use of benzene or benzene-containing materials; use of engineering controls and personal protective equipment; and other available exposure information. Overall, 38% (ranging from 3% for the earliest periods to 67% for the last period) of the estimates were based primarily on benzene monitoring data. In the absence of job-specific benzene monitoring data for a given calendar period, measurement results or exposure estimates for similar jobs and/or other calendar periods were used in conjunction with other exposure information to derive estimates. Estimated exposure levels are presented by industries and occupations. The highest average exposures during 1949-1987 were observed for the rubber and plastic industry (30.7 ppm), and for rubber glue applicators (52.6 ppm).

Indirect validation of a retrospective method of exposure assessment used in a nested case-control study of lung cancer and silica exposure.

Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed.

Occupational physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey.

A multiple-site case-control study of 15 cancers (stomach; colon; rectum; larynx; lung; melanoma; skin; female breast; male breast; cervix; ovary; uterus; prostate; testis; and bladder) was conducted to evaluate their association with occupational physical activity and socioeconomic status (SES). A hospital-based study population (3,486 male cases and 379 female cases, and 2,127 male and 244 female controls) was established in an oncological treatment center in Istanbul, Turkey, from 1979-84. Assessment of physical activity and SES was based on job titles held by the study subjects. Two measures of physical activity were developed based on energy expenditure and 'sitting time' during working hours. Observed risks were adjusted for age, smoking, and SES. Elevated risks were observed among workers who held sedentary jobs for cancers of the colon (odds ratio [OR] = 1.6), rectum (OR = 1.3), melanoma (OR = 1.9), male breast (OR = 1.4), prostate (OR = 5.0), and ovary (OR = 2.0). Cancers of the cervix and uterus showed significantly decreasing risks with decreased activity. Risks of cancers of the colon, rectum, larynx, ovary, and melanoma were enhanced after risks for physical activity indices were adjusted for SES, while the associations between physical activity and cancers of the prostate, cervix, and uterus were weakened after SES adjustment. Risks of melanoma rose significantly with both activity indices after SES adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Bias despite masked assessment of clinical outcomes when an outcome is defined as one of several component events.

Hypothetical examples are presented that show that bias can result from misclassification of clinical outcomes defined as one of several events, even though the assessment of each component event was masked. In one example, the effect of the overall misclassification is to make a treatment that reduces the risk appear to increase it; in another example, misclassification causes the overall treatment effect to appear stronger than it actually is. These anomalies are due to the fact that the misclassification of the overall outcome can be differential, even though the misclassification of the individual components is nondifferential.