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Purpose Several dusts and fibers have been classified by the International Agency for Research on Cancer (IARC) as carcinogens to humans. Others have been indicated as risk factors for lung cancer, but with no conclusive demonstration. We conducted an autopsy-based case–control study in Leningrad Province, Russia, to investigate the association of lung cancer risk with the exposure to 58 different dusts and fibers. Methods We identified 540 pathologically diagnosed lung cancer cases (474 males, 66 females) and 582 controls (453 males, 129 females) among subjects who had died in hospitals of Leningrad Province between 1993 and 1998. We retrieved subject-specific quantitative measurements of 15 organic, 15 synthetic and 28 natural inorganic dusts and fibers performed since 1950 in each work facility of the study area. We used unconditional logistic regression to compute sex-specific odds ratios (OR) and 95% confidence intervals (CI) for lung cancer adjusted for age, smoking, and residence. Results Nearly 90% of the study subjects had been exposed to one or more of the 58 dusts and fibers evaluated. Exposure above the specific maximum allowable concentrations (MACs) was frequent in this population, with average exposure intensity higher than MACs for 16% of the subjects. In males, lung cancer risk was increased among workers exposed to linen dust (OR = 3.68, 95% CI = 1.00–13.6) or unspecified dusts and fibers (OR = 1.44, 95% CI = 1.07–1.94). A nonsignificant increased risk, correlated with exposure intensity, was observed in males exposed to synthetic vitreous fibers (OR = 1.82, 95% CI = 0.88–3.75). Male subjects exposed to quartz dust had OR = 1.27 (95% CI = 0.83–1.93). In female subjects, a nonsignificant excess risk, which tended to increase with cumulative exposure, was observed for paper dust (OR = 1.77, 95% CI = 0.74–4.20) and for unspecified dusts and fibers (OR = 1.52, 95% CI = 0.77–3.03). Conclusion Most study subjects were exposed to dusts and fibers, often above the maximum allowable concentrations. We observed increased lung cancer risks for specific categories of dusts and fibers.

Purpose We evaluated the incidence of cancer in relation to pendimethalin exposure among pesticide applicators in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Pendimethalin is a widely used herbicide, intended for the control of most annual grasses and certain broadleaf weeds in most crops. Methods This study includes 9089 pendimethalin-exposed and 26,836 nonexposed pesticide applicators. At the time of enrollment (1993–1997), detailed information on pesticide exposure and potential confounders was obtained from a self-administered questionnaire. Poisson regression analysis was used to evaluate the effect of pendimethalin exposure, categorized into tertiles, on cancer incidence, controlling for the effects of potential confounding factors. Results Significant increased relative risks (RRs) for rectum cancer among subjects with the highest life-time pendimethalin exposure days were observed compared with both non-pendimethalin-exposed (RR = 3.5, 95% CI = 1.3–9.2) and low-pendimethalin-exposed (RR = 9.2, 95% CI = 1.1–81.1) applicators. We also observed an increased RR for rectum cancer when we used intensity-weighted lifetime pendimethalin exposure days as the exposure metric, using non-pendimethalin-exposed applicators as the referent group (RR = 3.5, 95% CI = 1.3–9.2, P trend = 0.04). Relative risk for lung cancer was also increased among subjects in the upper half of the highest tertile of life-time pendimethalin exposure days (RR = 5.2, 95% CI = 1.6–17.3, P trend = 0.03), compared with low-pendimethalin-exposed applicators. The association was more pronounced for adenocarcinoma of both rectum and lung. Conclusion Our findings suggest a possible association between pendimethalin exposure and incidence of rectum and lung cancers among pesticide applicators in the U.S.-based Agricultural Health Study.

PURPOSE: To examine the relationship between occupation, farm history, pesticide exposure and myeloma risk among blacks and whites in the U.S. METHODS: The study included 206 black and 367 white cases, newly diagnosed with myeloma between 1986 and 1989, and 967 black and 1,164 white controls from three U.S. areas. Information was obtained on socio-demographic factors, occupational and farm history, dietary factors, smoking, and medical history. Usual occupation and industry were coded according to standardized classification systems. A job/industry exposure matrix (JEM) was developed to estimate the level of occupational exposure to pesticides. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression. RESULTS: Farmers and farm workers had ORs of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An OR of 1.7 (95% CI 1.0-2.7) was observed among those who lived or worked on a farm where sheep were raised, whereas no increased risks were found for those who lived or worked on a farm where cattle, beef, pigs, or chickens were raised. We observed a modestly increased risk for pesticides overall (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were also observed among pharmacists, dietitians and therapists (OR 6.1, 95% CI 1.7-22.5), roofers (OR 3.3, 95% CI 1.1-9.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8) and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSION: Our study suggests a modest increased risk myeloma for exposure to pesticides. The observed increased risk among subjects who lived or worked on a farm where sheep were raised suggests that certain animal viruses may be involved in myeloma risk.

Objectives We evaluated the cancer incidence among over 49,000 pesticide applicators with exposure to either alachlor or atrazine in the Agricultural Health Study (AHS), a prospective cohort study of over 89,000 restricted use pesticide applicators and spouses of farmer applicators in Iowa and North Carolina, USA. Methods Comprehensive questionnaire data concerning lifestyle, occupations, personal and family medical history and use of 50 important agricultural pesticides, were collected prior to cancer incidence. Standardized incidence ratios (SIR) were estimated for those exposed and those not exposed to alachlor and for those exposed and those not exposed to atrazine, two important agricultural herbicides. Comparing the cancer experience of pesticide applicators from each state with that expected based on state specific incidence rates. Poisson regression was used to controlling for the effects of potential confounders (including age, sex, smoking, alcohol, education, state of residence, enrollment year, family history of cancer and the 5 [in the case of alachlor] or [10 in the case of atrazine] other pesticides most correlated with either alachlor or atrazine). Results A total of 1,466 incident malignant neoplasms occurred during the study period, 1993–2000. The SIR analysis showed a moderate deficit for all malignant neoplasm combined among both users and non-users of these herbicides. In Poisson regression analysis of alachlor, we found a significant increasing trend for the incidence of all lymphohematopoietic cancer and cumulative alachlor exposure (p for trend = 0.02). Incidence of leukemia and multiple myeloma was markedly increased among applicators in the highest exposure category. Similar analyses for other cancers did not suggest any association. For atrazine, no significant exposure-response trends were observed for any cancers or for all cancers combined, but non-significant positive trends were observed for cumulative atrazine exposures cancers of the rectum, bladder, and testicles. Conclusion Our findings suggests an association between alachlor exposure and increased incidence of lymphohematopoietic cancer in the Agricultural Health Study. Findings for atrazine are inconclusive at this time. Although the statistical power of the AHS is still low for some cancer evaluations after only 5.3 years of cohort follow-up, the comprehensive prospectively collected data, especially concerning pesticide exposures is an important strength of the study. Further details of the study are provided at our website: www.aghealth.org. Words = 415

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 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.

We conducted a population-based case-control study of bladder cancer in Iowa in 1986-1989 to evaluate the risk posed by tapwater containing chlorination byproducts. We combined information about residential history, drinking water source, beverage intake, and other factors with historical data from water utilities and measured contaminant levels to create indices of past exposure to chlorination byproducts. The study comprised 1,123 cases and 1,983 controls who had data relating to at least 70% of their lifetime drinking water source. After we adjusted for potential confounders, we calculated odds ratios for duration of chlorinated surface water of 1.0 (referent), 1.0, 1.1, 1.2, and 1.5 for 0, 1-19, 20-39, 40-59, and > or =60 years of use. We also found associations with total and average lifetime byproduct intake, as represented by trihalomethane estimates. Positive findings were restricted to men and to ever-smokers. Among men, odds ratios were 1.0 (referent), 1.1, 1.3, 1.5, and 1.9, and among ever-smokers, 1.0, 1.1, 1.3, 1.8, and 2.2, after adjustment for intensity and timing of smoking. Among nonsmoking men and women, regardless of smoking habit, there was no association. Among men, smoking and exposure to chlorinated surface water mutually enhanced the risk of bladder cancer. The overall association of bladder cancer risk with duration of chlorinated surface water use that we found is consistent with the findings of other investigations, but the differences in risk between men and women, and between smokers and nonsmokers, have not been widely observed.

Objective:To determine whether non-Hodgkin9s lymphoma mortality is associated with sunlight exposure. Design:Three case-control studies based on death certificates of non-Hodgkin9s lymphoma, melanoma, and skin cancer mortality examining associations with potential sunlight exposure from residence and occupation. Setting:24 states in the United States. Subjects:All cases were deaths from non-Hodgkin9s lymphoma, melanoma, and non-melanotic skin cancer between 1984 and 1991. Two age, sex, and race frequency matched controls per case were selected from non-cancer deaths. Main outcome measures:Odds ratios for non-Hodgkin9s lymphoma, melanoma, and skin cancer from residential and occupational sunlight exposure adjusted for age, sex, race, socioeconomic status, and farming occupation. Results:Non-Hodgkin9s lymphoma mortality was not positively associated with sunlight exposure based on residence. Both melanoma and skin cancer were positively associated with residential sunlight exposure. Adjusted odds ratios for residing in states with the highest sunlight exposure were 0.83 (95% confidence interval 0.81 to 0.86) for non-Hodgkin9s lymphoma, 1.12 (1.06 to 1.19) for melanoma, and 1.30 (1.18 to 1.43) for skin cancer. In addition, non-Hodgkin9s lymphoma mortality was not positively associated with occupational sunlight exposure (odds ratio 0.88; 0.81 to 0.96). Skin cancer was slightly positively associated with occupational sunlight exposure (1.14; 0.96 to 1.36). Conclusions:Unlike skin cancer and to some extent melanoma, non-Hodgkin9s lymphoma mortality was not positively associated with exposure to sunlight. The findings do not therefore support the hypothesis that sunlight exposure contributes to the rising rates of non-Hodgkin9s lymphoma. Key messages The incidence of non-Hodgkin9s lymphoma has risen rapidly in recent decades throughout much of the world Several investigators have hypothesised that increased exposure to sunlight may contribute to this rising incidence A study in the United States found that sunlight exposure based on residence and occupation was not positively associated with non-Hodgkin9s lymphoma The study found no evidence to support the hypothesis that sunlight contributes to the rising rates of non-Hodgkin9s lymphoma

An expanded cohort study of 74,828 benzene-exposed and 35,805 unexposed workers were followed during 1972 to 1987, based on a previous study in 12 cities in China. A small increase was observed in total cancer mortality among benzene-exposed compared with unexposed Workers (relative risk [RR] = 1-2). Statistically significant excesses were noted for leukemia (RR = 2.3), malignant lymphoma (RR = 4.5), and lung cancer (RR = 1.4). When risks were evaluated by leukemia subtype, only acute myelogenous leukemia was significantly elevated (RR = 3.1), although nonsignificant excesses were also noted for chronic myelogenous leukemia (RR = 2.6) and acute lymphocytic leukemia (RR = 2.3). A significant excess was also found for aplastic anemia. 19 refs., 5 tabs.

Previous occupational cohort studies of benzene-exposed workers have for the most part used only death certificates to validate diagnoses of workers developing leukemia and other hematopoietic and lymphoproliferative malignancies and related disorders (HLD). In a follow-up study of 74,828 benzene-exposed workers and a comparison group of 35,805 nonexposed workers from 12 cities in China, we sought to characterize clinicopathologically and to confirm diagnoses of all cases of HLD. Using medical records, laboratory hematology results, and histopathology, U.S. and Chinese expert hematopathologists, blinded to exposure status, carried out a detailed review using standardized evaluation forms. Key among the findings were a notable diversity of malignant and nonneoplastic hematopoietic and lymphoproliferative disorders, documentation of excess myelodysplastic syndromes among benzene workers, and widespread dyspoiesis involving all hematopoietic cell lines. As sophisticated clinicopathologic characterization and corresponding classification schemes for HLD become increasingly widespread, it is recommended that future epidemiologic investigations of benzene workers incorporate similarly detailed morphologic evaluation. In extending follow-up of this cohort of young workers, we will continue to use all available clinical, laboratory hematology, and pathology data as well as cytogenetic and biochemical markers to characterize various HLD outcomes. These careful surveillance mechanisms should also provide additional insight into carcinogenic mechanismsmore » of benzene and allow comparison of the molecular pathogenesis of HLD induced by benzene versus chemotherapy, radiation, or other exposure. 116 refs., 4 figs., 3 tabs.« less

In most occupational case-control studies, assessment of exposures is based on occupation and industry due to the lack of any other exposure information. The traditional approach to assessing exposures to specific substances is to estimate exposure for each occupation/industry combination. A modified procedure that substantially reduces the effort necessary to complete such assessments is described. In this procedure, exposure levels (none, low, medium, and high) are estimated for each occupation and industry separately. Numeric weights are assigned to these exposures levels. Final estimates for each occupation/industry combination are derived using exposure weights for occupations and industries. This method was applied to a case-control data set to estimate levels of silica exposure for the work histories of subject. The traditional method required 13,445 individual evaluations while the new approach required only 2,000 estimates. Results from the new approach were compared with those from the ...

BACKGROUND: DNA hypomethylation has been suggested to cause genomic instability and increase cancer risk. We aimed to test the hypothesis that DNA hypomethylation is associated with increased risk of bladder cancer. METHODS: We measured cytosine methylation (5-mC) content in genomic DNA from blood cells from patients with bladder cancer enrolled in a large case-control study in Spain between Jan 1, 1998, and Dec 31, 2001. Cases were men and women with newly diagnosed and histologically confirmed urothelial carcinoma of the bladder. Controls were selected from patients admitted to the same hospital for diseases or conditions unrelated to smoking or other known risk factors for bladder cancer. Controls were individually matched to cases on age (within 5 years), sex, race, and area of hospital referral. 5-mC content was measured in leucocyte DNA by use of a combination of high-performance capillary electrophoresis, Hpa II digestion, and densitometry. Data on demographics, 34 polymorphisms in nine folate metabolism genes, and nutritional intake of six B vitamins (including folate), alcohol, and smoking were assessed as potential confounders. Relative 5-mC content was expressed as a percentage (%5-mC) with respect to the total cytosine content (the sum of methylated and non-methylated cytosines). The primary endpoint was median %5-mC DNA content. FINDINGS: %5-mC was measured in leucocyte DNA from 775 cases and 397 controls. Median %5-mC DNA was significantly lower in cases (3.03% [IQR 2.17-3.56]) than in controls (3.19% [2.46-3.68], p=0.0002). All participants were subsequently categorised into quartiles by %5-mC content in controls. When the highest quartile of %5-mC content was used as the reference category (Q4), the following adjusted odds ratios (OR) and 95% CI were recorded for decreasing methylation quartiles: OR(Q3) 2.05 (95% CI 1.37-3.06); OR(Q2) 1.62 (1.07-2.44); and OR(Q1) 2.67 (1.77-4.03), p for trend

Objectives This study sought to ascertain the risk of thyroid cancer in relation to occupational exposure to ionizing radiation and extremely low-frequency magnetic fields (ELFMF) in a cohort representative of Sweden’s gainfully employed population. Methods A historical cohort of 2 992 166 gainfully employed Swedish male and female workers was followed up from 1971 through 1989. Exposure to ELFMF and ionizing radiation was assessed using three job exposure matrices based on industrial branch or occupational codes. Relative risks (RR) for male and female workers, adjusted for age and geographic area, were computed using log-linear Poisson models. Results Occupational ELFMF exposure showed no effect on the risk of thyroid cancer in the study. However, female workers exposed to high intensities of ionizing radiation registered a marked excess risk (RR 1.85, 95% confidence interval (95% CI) 1.02–3.35]. This trend was not in evidence among the men. Conclusions While the study confirms the etiologic role of ionizing radiation, with a higher incidence of thyroid cancer being recorded for the most-exposed female workers, our results do not support the possibility of occupational exposure to ELFMF being a risk factor for the development of thyroid cancer.

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.