The exposure metric: does including time since exposure in the calculation of working lifetime exposure provide a better understanding of disease risk than the cumulative exposure?

BACKGROUND: When exposure measurements are available for occupational epidemiology studies, the cumulative exposure (the sum of the products of duration and exposure intensity at all jobs) is generally selected as the summary metric for chronic diseases. For silica exposures, a metric that weights each exposure by the number of years since it occurred has been suggested as more biologically relevant. Comparative reports of analyses using both metrics have not been found in the literature, however. METHODS: We calculated both metrics for silica exposure, and evaluated exposure-response relations for lung cancer and silicosis in two separate case-control studies. RESULTS: Generally the results were consistent, due to the high correlation between the two metrics and the fact that the rate of time away from work during the employment years was low. CONCLUSION: The significant relation between exposure and silicosis using the weighted metric provides additional point estimates of risk, adding to the understanding of exposure-response.

Occupation and bladder cancer in a hospital-based case-control study in Spain.

OBJECTIVES: We investigated the association between occupation and bladder cancer in a hospital-based case-control study conducted in Spain. METHODS: 1219 patients with transitional cell carcinoma of the urinary bladder and 1271 controls selected from 18 hospitals in Spain between June 1998 and September 2000 provided detailed information on life-time occupational history, smoking habits, medical history, and other factors. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for each occupation and industry, adjusting for age, hospital region, smoking duration, and employment in a high-risk occupation for bladder cancer. RESULTS: Statistically significant increased risks were observed among men employed as machine operators in the printing industry (OR 5.4; 95% CI 1.6 to 17.7), among men employed in the transportation equipment industry (OR 1.6; 95% CI 1.1 to 2.6) and among those who had worked for >/=10 years in the electrical/gas/sanitary services (OR 3.9; 95% CI 1.5 to 10.4) and in hotels and other lodgings (OR 3.1; 95% CI 1.3 to 7.3). Men who worked as miscellaneous mechanics and repairers (OR 2.0; 95% CI 1.1 to 3.6) and as supervisors in production occupations (OR 2.1; 95% CI 1.2 to 3.6) also had excess risks for bladder cancer. Male farmers and those who worked in crop and livestock production had decreased risks for bladder cancer. We found no significant associations between occupation or industry and bladder cancer risk among women. CONCLUSIONS: We did not observe excess bladder cancer risk for many of the occupations identified as being a priori at high risk. Examination of more detailed job exposure information should help clarify these associations.

Work in the textile industry in Spain and bladder cancer.

BACKGROUND/OBJECTIVE: Textile manufacturing is a complex industry that has frequently been associated with bladder cancer. However, results have not been consistent. This study investigated the risk of bladder cancer in Spanish textile workers. METHODS: We analysed data from a multicentre hospital-based case-control study carried out in Spain (1998-2001) including 1219 cases of bladder cancer and 1271 controls. Of those, 126 cases and 122 controls reported a history of employment in the textile industry. Lifetime occupational history was obtained using a computer-assisted personal interview. Occupations, locations and materials used in the textile industry were assessed using a detailed questionnaire and expert assessment. RESULTS: Overall, no increased risk of bladder cancer was found for textile workers, including duration of employment analysis. Increased risks were observed for weavers (OR = 1.82, 95% CI 0.95 to 3.47), for workers in winding/warping/sizing (OR 4.11, 95% CI 1.58 to 10.71) and for those exposed to synthetic materials (OR 1.89, 95% CI 1.00 to 3.56). Working for more than 10 years appeared to be associated with an increased risk for weavers (OR 2.27, 95% CI 0.97 to 5.34), for those who had ever worked in winding/warping/sizing (OR 11.03, 95% CI 1.37, 88.89), for workers in the weaving room (OR 2.94, 95% CI 1.24 to 7.01) and for those exposed to synthetic (OR 2.62, 95% CI 1.14 to 6.01) or cotton (OR 2.00, 95% CI 1.04 to 3.87) materials. Statistically significant higher risks were also found for specific combinations of occupations or locations with exposure to synthetics and cotton. CONCLUSIONS: There was no overall increased risk for textile workers, but increased risks were found for specific groups of workers. Our findings indicate that observed risks in previous studies may be better evaluated by analysis of materials used or section worked within the industry and occupation.

Systemic autoimmune disease mortality and occupational exposures.

OBJECTIVE: To generate hypotheses regarding occupational exposures that may cause systemic autoimmune diseases. METHODS: Based on examination of US death certificates, we identified deaths in 26 states for which a cause was listed as rheumatoid arthritis (RA) (n = 36,178), systemic lupus erythematosus (SLE) (n = 7,241), systemic sclerosis (n = 5,642), or other systemic autoimmune disease (n = 4,270). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to estimate associations between occupation and death from any systemic autoimmune disease, and from RA, SLE, and systemic sclerosis, specifically. Additionally, we estimated risks associated with occupational exposures, which were assigned using job-exposure matrices. RESULTS: A broad array of occupations was associated with death from systemic autoimmune diseases, including several of a priori interest. Farming occupation was associated with death from any systemic autoimmune disease (OR 1.3 [95% CI 1.2-1.4]), and increased risk was also seen with occupational exposure to animals and pesticides. Several industrial occupations were associated with death from any systemic autoimmune disease, including mining machine operators (OR 1.3 [95% CI 1.1-1.5]), miscellaneous textile machine operators (OR 1.2 [95% CI 1.0-1.4]), and hand painting, coating, and decorating occupations (OR 1.8 [95% CI 1.0-2.9]). These occupations were also significantly associated with death from the specific autoimmune diseases examined. Certain occupations entailing exposure to the public, such as teachers, were associated with systemic autoimmune disease-related death, whereas others, such as waiters and waitresses, were not. CONCLUSION: Our results suggest that death from systemic autoimmune diseases may be associated with occupational exposures encountered in farming and industry. The hypotheses generated in this study provide leads for future research on determinants of these diseases.

Lung cancer among silica-exposed workers: the quest for truth between chance and necessity.

BACKGROUND: In 1997, IARC upgraded crystalline silica to a Group 1 human carcinogen. However, the IARC report itself acknowledged variations in risk depending on inherent characteristics of the crystalline silica or external factors affecting its biological activity or distribution of its polymorphs. METHODS: We reviewed silica physical and physico-chemical properties and how such properties may affect its interaction with the target cells. Studies of silica, silicosis and lung cancer published from 1997 onwards are then reviewed in the search of any new advances in knowledge about silica carcinogenicity. Finally, other possible confounding factors contributing to inconsistent findings on silica, silicosis, and lung cancer are reviewed. RESULTS: Host factors, physico-chemical characteristics of the surface of silica particles, exposure circumstances, and the mineral ore composition experimentally affect the ability of silica particles of inducing release of reactive oxygen species (ROS) and TNF-alpha by alveolar macrophages, possibly accounting for the great variation in lung cancer risk among dust exposed workers across the individual studies. Most recent epidemiological studies do not consider such complex pattern of modifying factors, and they keep replicating inconsistent findings. The hypothesis of a silicosis-mediated pathway, although more consistent from an epidemiological perspectives, and reassuring in terms of the effectiveness of current standards in preventing lung cancer risk among silica exposed workers, does not seem to explain elevated risks at low silica exposure levels. CONCLUSION: Future studies of lung cancer risk among workers exposed to silica-containing dust should consider measurement of ROS and TNF-alpha release by workplace dust samples as intermediate end-points predicting lung cancer risk better than silica concentration, allowing to more effectively address preventive action.

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.

Risk of lymphatic or haematopoietic cancer mortality with occupational exposure to animals or the public.

BACKGROUND: Occupational exposure to animals or the public could result in exposure to infectious agents, which may play a role in the aetiology of lymphohaematopoietic (LH) cancers. AIMS: To conduct a population based, case-control study of death certificate data from 1984 to 1998 in 24 US states in order to evaluate the risk of mortality from LH neoplasms associated with occupational exposure to animals or the public. METHODS: Cases were selected as those with an underlying cause of death of non-Hodgkin's lymphoma (NHL, n = 72,589), Hodgkin's disease (HD, n = 5479), multiple myeloma (n = 35,857), or leukaemia (n = 68,598); 912 615 controls were randomly selected from all remaining deaths, frequency matched on age, sex, race, and geographic region. RESULTS: Occupational exposure to animals was associated with modest increased risks of mortality from all four LH cancers; these associations varied by region. Occupational exposure to the public was associated with only negligible increased risk with LH cancer outcomes. Occupations involving animal exposure were predominantly agricultural, and the risks associated with employment in the livestock industry exceeded the corresponding risks associated with the crop industry for all outcomes except HD. CONCLUSIONS: Increased risks of NHL, HD, multiple myeloma, and leukaemia were associated with occupations that involved animal exposure. Regional differences in risk imply that the risks may be associated with exposure to specific livestock or farming practices. However, these associations may be confounded by other farming related exposures, such as pesticides. Because the use of death certificates to classify occupation may result in misclassification during aetiologically relevant time periods, these hypotheses should be further explored in studies with detailed information on lifetime occupation.

Occupation and lung cancer risk in Leningrad Province, Russia.

To investigate the association between occupation and lung cancer risk in Leningrad Province, Russia, we identified 540 pathologically diagnosed lung cancer cases (474 males and 66 females) and 582 controls (453 males and 129 females) from the 1993-1998 autopsy records of the 88 state hospitals of the Province. Lifetime occupational histories were obtained from personal records coded according to the standard Russian occupational classification system. Lung cancer risk was increased in workers in the manufacturing industry, particularly in the food industry and wholesale/retail trade and in the miscellaneous manufacturing industry. An increased risk was also found in subjects employed in chemical and metal production for 10 years or more. When we considered the association between specific occupations and lung cancer, waste incineration operators and loaders exhibited an excess risk that increased with employment duration. The present study, which is the first to evaluate the risk of lung cancer by occupation in Russia, suggests the presence in Leningrad Province of exposure in the workplace to lung carcinogens that require further characterization to develop targeted and effective preventive measures.

Disease and injury among participants in the Agricultural Health Study.

The Agricultural Health Study (www.aghealth.org) is a cohort of 89,658 pesticide applicators and their spouses from Iowa and North Carolina assembled between 1993 and 1997 to evaluate riskfactorsfor disease in ruralfarm populations. This prospective study is just now reaching sufficient maturity for analysis of many disease endpoints. Nonetheless, several analyses have already provided interesting and important leads regarding disease patterns in agricultural populations and etiologic clues for the general population. Compared to the mortality experience of the general population in the two states (adjusted for race, gender, age and calendar time), the cohort experienced a very low mortality rate overall and for many specific causes and a low rate of overall cancer incidence. A few cancers, however, appear elevated, including multiple myeloma and cancers of the lip, gallbladder, ovary, prostate, and thyroid, but numbers are small for many cancers. A study of prostate cancer found associations with exposure to several pesticides, particularly among individuals with a family history of prostate cancer. Links to pesticides and other agricultural factors have been found for injuries, retinal degeneration, and respiratory wheeze. Methodological studies have determined that information collected by interview is unbiased and reliable. A third round of interviews scheduled to begin in 2005 will collect additional information on agricultural exposures and health outcomes. The study can provide data to address many health issues in the agricultural community. The study investigators welcome collaboration with interested scientists.

Occupation and risk of stomach cancer in Poland.

BACKGROUND: In spite of the dramatic decline in the incidence of stomach cancer in the twentieth century, Poland has one of the highest rates in the world. AIMS: To evaluate the risk of stomach cancer by grouped occupations and industries, as well as by some specific occupational exposures. METHODS: Cases (n = 443) were newly diagnosed with stomach adenocarcinomas between 1994 and 1996. Controls (n = 479) were randomly selected from the general population in Warsaw. RESULTS: Only a few occupations and industries were associated with significantly increased risks of stomach cancer. The most suggestive finding was for work in the leather goods industry. Risk was also significantly increased among men working in fabricated metal production and among women ever employed as managers and governmental officials. Men ever employed as teaching professionals and women employed as technical and science professionals had significantly decreased risks of stomach cancer. Among men, a significant positive trend in risk with duration of employment was observed for work in the leather industry and special trade construction. No significantly increased risks were observed for specific exposures assessed by a job-exposure matrix or by self-reports. However among men there were non-significantly increased risks with 10 or more years exposure to asbestos, metal dust, and nitrosamines assessed by a job-exposure matrix. CONCLUSIONS: Employment in the leather goods industry, special trade construction, and metal fabrication was associated with an increased risk of stomach cancer among men. However, there were only weak associations with specific exposures. Occupational exposures do not contribute substantially to the high rates of stomach cancer in Poland.

Occupation and the risk of adult glioma in the United States.

OBJECTIVE: Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. METHODS: Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. RESULTS: Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. CONCLUSIONS: This is our first analysis of occupation and will guide future exposure-specific assessments.

Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer.

OBJECTIVE: To confirm the very high male:female ratios previously observed among Spanish bladder cancer patients and to assess gender differences in tumoral characteristics, diagnostic procedures, and treatment in a large series of consecutive bladder cancer patients. PATIENTS AND METHODS: All newly diagnosed bladder cancer patients (n=615) in 17 Spanish hospitals, between 1997-2000, were included. Information was collected both through personal interviews to patients and from medical records using a structured form. RESULTS: Seventy-six percent of tumours were superficial. The male:female ratio was 6.7 and it was similar for superficial and infiltrating tumours. Women were older than men at the diagnosis of bladder cancer (68.2+/-9.4 years versus 65.7+/-9.7 years, p=0.01). Ten percent of superficial tumours in women, versus 3% in men, were classified as "other histological types" (p=0.008). T1GIII tumours were more frequent among men (17% versus 7%, p=0.047). On the other hand, women were more likely to present with 0a-stage tumours (48.6% versus 35.5%, p=0.04), multiple tumours (50% versus 29%, trend test: 0.005), multi-centric tumours (54% versus 38%, p=0.019), and larger infiltrating masses (5.2 cm versus 3.8 cm, p=0.03) than men. Among 0a-stage tumours, only 23% of women compared to 54% of men received transurethral resection (TUR) alone (p=0.002). Women were almost five-fold more likely to receive additional therapies to TUR (p=0.004) after adjusting for age, geographical area, stage, tumoral size, nuclear grade, and multiplicity. CONCLUSION: The study confirms the very high male:female ratio of bladder cancer in Spain. We found substantial differences in the pathological characteristics of tumours from men and women. There was a tendency for women to receive more frequently non-standard, more aggressive, therapy than men.

Occupation and the risk of lung cancer by histologic types and morphologic distribution: a case control study in Turkey.

BACKGROUND: The lung cancer incidence rate in Turkey has been increasing since the early 1980's. Etiology of lung cancer could be affected by differences in lifestyle, working conditions, and occupational exposures. OBJECTIVES: A hospital based case-control study was conducted in Turkey to provide information on the role that occupation plays in lung cancer etiology and the relationship between occupations and histologic types and the morphologic distribution of lung cancer. METHODS: A total of 1,354 male cases and 1,519 controls were analysed. Basic information was obtained from patients from a standardised questionnaire. Occupational titles of the subjects were classified by standard occupational and industrial codes. Age- and smoking-adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Excess lung cancer occurred among fire-fighters (OR: 6.8, CI: 1.3-37.4), drivers (OR: 1.4, CI: 1.1-2.0), textile workers (OR: 1.7, CI: 1.1-2.7), water treatment plant workers (OR: 2.2, CI: 1.1-4.3) and highway construction workers (OR: 1.5, CI: 1.0-2.5). Workers in the textile and grain milling industries were shown to have a significant excess risk of squamous cell carcinoma. Textile workers, and those working at water treatment plants had excess risk of small cell carcinoma. Construction workers had excess risk of adenocarcinoma. Fire-fighters and workers at textile plants, grain mills, water treatment plants, and in steel production were exposed to a high risk of peripheral tumors while the risk of central tumors was excessive among drivers and highway construction workers. CONCLUSIONS: The risk of lung cancer was associated with several occupations and peripheral located tumors and squamous lung cancer was the most common type.

Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study.

OBJECTIVES: To explore whether mortality from female breast, ovarian, colon, and prostate cancer were negatively associated with exposure to sunlight. METHODS: A death certificate based case-control study of mortality was conducted into five cancers: female breast, ovarian, colon, prostate, and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from these cancers between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded deaths from cancer and certain neurological diseases. Multiple logistic regression was used in a model that included age, sex, race, residential exposure to sunlight (based on region), and socioeconomic status, occupational exposure to sunlight, and physical activity (the last three based on usual occupation). RESULTS: Residential exposure to sunlight was negatively and significantly associated with mortality from female breast, ovarian, prostate, and colon cancer. Only female breast and colon cancer, however, also showed significant negative associations with jobs with the highest occupational exposure to sunlight (odds ratio (OR) 0.82 (95% confidence interval (95% CI) 0.70 to 0.97) for female breast cancer; OR 0.90 (95% CI 0.86 to 0.94) for colon cancer). For both cancers, the negative association with occupational sunlight was greatest in the geographical region of highest exposure to sunlight and was independent of physical activity on the job. Non-melanoma skin cancer, as expected, was positively associated with both residential and occupational sunlight. CONCLUSIONS: In this exploratory study, unlike mortality from non-melanoma skin cancer, mortality from female breast cancer and colon cancer were negatively associated with both residential and occupational sunlight.

Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden.

We investigated effects of occupational physical activity on relative risk for prostate cancer. From Swedish nationwide censuses in 1960 and 1970, we defined two cohorts of men whose occupational titles allowed classification of physical activity levels at work in 1960 (n=1,348,971) and in 1970 (n=1,377,629). A third cohort included only men whose jobs required a similar level of physical activity in both 1960 and 1970 (n=673,443). The incidence of prostate cancer between 1971 and 1989 was ascertained through record linkage to the Swedish Cancer Register. A total of 43,836, 28,702, and 19,670 prostate cancers, respectively, occurred in the three cohorts. In all three cohorts, the relative risk for prostate cancer increased with decreasing level of occupational physical activity (P<0.001), using Poisson regression. Among men with the same physical activity levels in 1960 and 1970, the rate ratio was 1.11 for men with sedentary jobs as compared with those whose jobs had very high/high activity levels after adjustment for age at follow-up, calendar year of follow-up and place of residence (95% CI 1.05-1.17; P for trend <0.001). There was no association between occupational activity and prostate cancer mortality. Since we had no data on other potential risk factors the observed associations for both incidence and mortality might have been confounded. Further studies are needed to better understand the potential role of physical activity for prostate cancer.

Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma.

Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (>90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type 1 (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% CI = 1.0-3.0). Those exposed to wood dust for >10 years had an adjusted RR of 2.4 (95% CI = 1.1-5.0; p(trend) = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93-2.2). Those exposed to formaldehyde for >10 years had an adjusted RR of 1.6 (95% CI = 0.91-2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86-1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis.

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.

Proportionate mortality among US migrant and seasonal farmworkers in twenty-four states.

BACKGROUND: US migrant and seasonal farmworkers may be exposed to potentially carcinogenic pesticides and other agents. Little epidemiologic research has been conducted on this population. METHODS: We examined the proportionate mortality of 26,148 subjects (14,631 white men (WM), 7,299 nonwhite men (NM), 1,081 white women (WW), and 3,137 nonwhite women (NW)) who were identified as farmworkers on death certificates from 24 US states during 1984-1993. RESULTS: Farmworkers had significantly elevated proportionate mortality from injuries, tuberculosis, mental disorders, cerebrovascular disease, respiratory diseases, ulcers, hypertension (NW), and cirrhosis (NW). There was significantly reduced mortality from infectious diseases (other than tuberculosis), endocrine disorders, nervous system diseases, pneumoconioses, arteriosclerotic heart disease (WM), and all cancers combined. Proportionate cancer mortality analyses found excess cancers of the buccal cavity, larynx, esophagus, stomach, skin (NW), and cervix, and deficits for cancers of the colon, breast, kidney, pancreas (NW), and lymphohematopoietic system. CONCLUSIONS: The excess deaths from injuries, respiratory disease, and stomach cancer, and the deficits of colon cancer and arteriosclerotic heart disease among farmworkers, are consistent with typical mortality patterns previously observed among farm owner/operators. The excess buccal, laryngeal, esophageal, and cervical cancers, and the deficits of breast cancer and lymphohematopoietic cancers have not generally been observed in studies of farm owner/operators.

Occupation and the risk of laryngeal cancer in Turkey.

OBJECTIVES: A hospital-based case-referent study was conducted in Turkey to provide further information on occupational risk factors and laryngeal cancer. METHODS: Among 7631 cancer cases seen at an oncology treatment center between 1979 and 1984, 958 laryngeal cancer cases were identified among men. Occupational history, tobacco and alcohol use, and demographic data were obtained from patients with a standardized questionnaire. Special 7-digit standard occupational and industrial codes were created to classify the job and industrial titles of the subjects. After exclusions, 940 laryngeal cancer cases and 1519 referents were available for study. Age-, smoking- and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: Excess laryngeal cancer occurred among guards (OR 1.5, 95% CI 1.1-2.1), production supervisors (OR 1.8, 95% CI 1.1-3.1), textile workers (OR 1.9, 95% CI 1.2-3.3), drivers (OR 1.7, 95% CI 1.1-2.4), construction workers (OR 1.7, 95% Cl 1.2-2.6), and workers in grain mills (OR 3.1, 95% CI: 1.3-7.6), trade unions (OR 3.6, 95% CI: 1.1-11.7) and local government services (OR 4.7, 95% CI 1.7-12.5). Supraglottic cancer was excessive among the textile workers, construction workers, and local government laborers, all with potential dust exposure. The risks of the general managers, electricians, and workers from industries such as pharmaceutical production, industrial machinery production, electric utilities, and retail services were lower than expected. CONCLUSIONS: The risk of laryngeal cancer was associated with several occupations, and supraglottic larynx cancer appears to be more common among workers in dusty occupations and industries.

Benzene and lymphohematopoietic malignancies in humans.

BACKGROUND: Quantitative evaluations of benzene-associated risk for cancer have relied primarily on findings from a cohort study of highly exposed U.S. rubber workers. An epidemiologic investigation in China (NCI/CAPM study) extended quantitative evaluations of cancer risk to a broader range of benzene exposures, particularly at lower levels. METHODS: We review the evidence implicating benzene in the etiology of hematopoietic disorders, clarify methodologic aspects of the NCI/CAPM study, and examine the study in the context of the broader literature on health effects associated with occupational benzene exposure. RESULTS: Quantitative relationships for cancer risk from China and the U.S. show a relatively smooth increase in risk for acute myeloid leukemia and related conditions over a broad dose range of benzene exposure (below 200 ppm-years mostly from the China study and above 200 ppm-years mostly from the U.S. study). CONCLUSIONS: Risks of acute myeloid leukemia and other malignant and nonmalignant hematopoietic disorders associated with benzene exposure in China are consistent with other information about benzene exposure, hematotoxicity, and cancer risk, extending evidence for hematopoietic cancer risks to levels substantially lower than had previously been established. Published 2001 Wiley-Liss, Inc.