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An algorithm developed to estimate pesticide exposure intensity for use in epidemiologic analyses was revised based on data from two exposure monitoring studies. In the first study, we estimated relative exposure intensity based on the results of measurements taken during the application of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n = 17). Modifications to the algorithm weighting factors were based on geometric means (GM) of post-application urine concentrations for applicators grouped by application method and use of chemically-resistant (CR) gloves. Measurement data from a second study were also used to evaluate relative exposure levels associated with airblast as compared to hand spray application methods. Algorithm modifications included an increase in the exposure reduction factor for use of CR gloves from 40% to 60%, an increase in the application method weight for boom spray relative to in-furrow and for air blast relative to hand spray, and a decrease in the weight for mixing relative to the new weights assigned for application methods. The weighting factors for the revised algorithm now incorporate exposure measurements taken on Agricultural Health Study (AHS) participants for the application methods and personal protective equipment (PPE) commonly reported by study participants.

BACKGROUND: Recent findings indicate that vitamin D obtained from ultraviolet (UV) exposure may reduce the risk of several different cancers. Vitamin D is metabolized to its active form within the kidney, which is the major organ for vitamin D metabolism and activity. Because both the incidence of renal cell carcinoma (RCC) and the prevalence of vitamin D deficiency have increased over the past few decades, in the current study, the authors explored whether occupational UV exposure was associated with RCC risk. METHODS: A hospital-based, case-control study of 1097 patients with RCC (cases) and 1476 controls was conducted in 4 Central and Eastern European countries. Demographic and occupational information was collected to examine the association between occupational UV exposure and RCC risk. RESULTS: A significant reduction (24%-38%) in the risk of RCC was observed with increasing occupational UV exposure among men who participated in the study. No association between UV exposure and RCC risk was observed among women who participated. When the analyses were stratified by latitude as another estimate of sunlight intensity, a stronger reduction (71%-73%) in the risk of RCC was observed between UV exposure and cancer risk among men who resided at the highest latitudes. CONCLUSIONS: The current results suggested that, among men, there is an inverse association between occupational UV exposure and the risk of RCC. Replication studies are warranted to confirm these results. Cancer 2010. Published 2010 by the American Cancer Society.

Terbufos is the fourth most commonly used organophosphate insecticide (OP) in the United States. Terbufos has not been demonstrated to be carcinogenic in rodents, although non-arsenical insecticides, including OPs, have been associated with excess cancer in epidemiologic studies. We investigated associations between use of terbufos and the incidence of cancer.The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Terbufos intensity-weighted lifetime exposure-days were defined as (lifetime exposure-days) x (exposure intensity score). Cases include all first primary cancers diagnosed between enrollment and December 31, 2005. Hazard ratios (HR) and 95% CI were calculated with Cox proportional hazards models, adjusting for potential confounders.Overall cancer risk was slightly increased among terbufos users [HR 1.21 (1.06-1.37)]. Suggestive associations were observed between terbufos use and cancers of the prostate (HR(highest tertile) = 1.21; 95% CI = 0.99-1.47) and lung (HR(middle tertile) = 1.45; 95% CI = 0.95-2.22) and leukemia (HR(middle tertile) = 2.38; 95% CI = 1.35-4.21) and non-Hodgkin's lymphoma (HR(middle tertile) = 1.94; 95% CI = 1.16-3.22), although the exposure-response gradients were non-monotonic and p for trends were not significant.We found suggestive associations between occupational terbufos use and several cancer sites. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.

We investigated the association between occupational exposure to extremely low-frequency magnetic fields (MFs) and the risk of glioma and meningioma. Occupational exposure to MF was assessed for 489 glioma cases, 197 meningioma cases, and 799 controls enrolled in a hospital-based case–control study. Lifetime occupational history questionnaires were administered to all subjects; for 24% of jobs, these were supplemented with job-specific questionnaires, or “job modules,” to obtain information on the use of electrically powered tools or equipment at work. Job-specific quantitative estimates for exposure to MF in milligauss were assigned using a previously published job exposure matrix (JEM) with modification based on the job modules. Jobs were categorized as ≤1.5 mG, >1.5 to 1.5 mG; (3) cumulative lifetime exposure; and (4) average lifetime exposure. Odds ratios (ORs) were calculated using unconditional logistic regression with adjustment for the age, gender, and hospital site. The job modules increased the number of jobs with exposure ≥3.0 mG from 4% to 7% relative to the JEM. No statistically significant elevation in ORs or trends in ORs across exposure categories was observed using four different exposure metrics for the three tumor types analyzed. Occupational exposure to MFs assessed using job modules was not associated with an increase in the risk for glioma, glioblastoma, or meningioma among the subjects evaluated in this study.

Epidemiologic studies increasingly rely on improved exposure assessments to characterize pesticide exposures in agricultural populations. A subset of private pesticide applicators in the AHS epidemiological cohort was monitored around the time of their agricultural use of 2,4-D and chlorpyrifos to assess exposure levels and potential exposure factors. Measurements included pre- and post-application urine samples, and patch, hand wipe, and personal air samples. Broadcast or hand spray application methods were used by applicators for 2,4-D products. Chlorpyrifos products were applied using spray applications and in-furrow application of granular products. Geometric mean (GM) values for 69 2,4-D applicators were 7.8 and 25 µg/L in pre- and post-application urine, respectively (p < 0.05 for difference); 0.39 mg for estimated hand loading; 2.9 mg for estimated body loading; and 0.37 µg/m3 for concentration in personal air. Significant correlations were found between all media for 2,4-D. GM values for 17 chlorpyrifos applicators were 11 µg/L in both pre- and post-application urine for the 3,5,6-trichloro-2-pyridinol metabolite, 0.28 mg for body loading, and 0.49 µg/m3 for air concentration. Only 53% of the chlorpyrifos applicators had measureable hand loading results; their median hand loading was 0.02 mg. Factors associated with differences in 2,4-D measurements included application method and glove use; and, for hand spray applicators, use of adjuvants, equipment repair, duration of use, and contact with treated vegetation. Spray applications of liquid chlorpyrifos products were associated with higher measurements than in-furrow granular product applications. This study provides information on exposures and possible exposure determinants for several application methods commonly used by farmers in the cohort and will provide information to assess and refine exposure classification in the Agricultural Health Study. Results may also be of use in pesticide safety education for reducing exposures to applied pesticides.

The transforming growth factor-beta (TGF-β) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF-β signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFB1 (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case-control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan-Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle-invasive tumors, we found a significant association between TGFBR1-rs868 and disease-specific mortality with an allele dosage effect (p-trend = 0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of TGFBR1-rs868 with outcome should be validated in independent patient series. © 2008 Wiley-Liss, Inc.

A population-based case-control study involving 601 incident cases of non-Hodgkin lymphoma (NHL) and 717 controls was conducted in 1996–2000 among Connecticut women to examine associations with exposure to organic solvents. A job-exposure matrix was used to assess occupational exposures. Increased risk of NHL was associated with occupational exposure to chlorinated solvents (odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8) and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Those ever exposed to any organic solvent in work settings had a borderline increased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover, a significantly increased risk was observed for those with average probability of exposure to any organic solvent at medium-high level (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased risk was also found for ever exposure to formaldehyde (OR = 1.3, 95% CI: 1.0, 1.7) in work settings. Risk of NHL increased with increasing average intensity (P = 0.01), average probability (P

Experimental studies suggest that increased urination frequency may reduce bladder cancer risk if carcinogens are present in the urine. Only 2 small studies of the effect of increased urination frequency on bladder cancer risk in humans have been conducted with conflicting results. Our purpose was to evaluate the effect of urination frequency on risk of bladder cancer in a large, multicenter case–control study. We analyzed data based on interviews conducted with 884 patients with newly diagnosed, bladder cancer and 996 controls from 1998 to 2001 in Spain. We observed a consistent, inverse trend in risk with increasing nighttime voiding frequency in both men (p = 0.0003) and women (p = 0.07); voiding at least 2 times per night was associated with a significant, 40–50% risk reduction. The protective effect of nocturia was apparent among study participants with low, moderate and high water consumption. The risk associated with cigarette smoking was reduced by nocturia. Compared with nonsmokers who did not urinate at night, current smokers who did not urinate at night had an OR of 7.0 (95% CI = 4.7–10.2), whereas those who voided at least twice per night had an OR of 3.3 (95% CI = 1.9–5.8) (p value for trend = 0.0005). Our findings suggest a strong protective effect of nocturia on bladder cancer risk, providing evidence in humans that bladder cancer risk is related to the contact time of the urothelium with carcinogens in urine. Increased urination frequency, coupled with possible dilution of the urine from increased water intake, may diminish the effect of urinary carcinogens on bladder cancer risk.

Captan is a widely used antifungal pesticide whose potential to cause cancer in humans is uncertain.We evaluated the incidence of cancer among pesticide applicators exposed to captan in the Agricultural Health Study. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997.Of the 48,986 applicators enrolled 4,383 (9%) had applied captan. Median follow-up time was 9.14 years. Poisson regression analysis was used to estimate relative risks (RR) for cancer subtypes by tertiles of captan exposure. We investigated risk for all cancers combined and sites of cancer for which at least 15 cases occurred among captan-exposed applicators. These sites included cancers of the prostate, lung, and colon, blood-related cancers, and colorectal cancers. During follow-up 2,912 incident primary cases of cancer were identified. No association between the highest tertile of captan exposure (67.375 intensity-weighted days) and development of all cancers (RR = 0.89; 95% CI, 0.71-1.13) or cancer of any specific site was observed.Although our study is limited by low numbers of observed cancer cases and follow-up time of 9.14 years, it does not provide evidence of an increased risk for the development of cancer at the investigated sites.

Trifluralin, 2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline, is a 2,6-dinitro herbicide widely used to control annual grasses and broadleaf weeds in agricultural settings. The association between trifluralin use and common cancer incidence was evaluated among 50,127 private and commercial pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina. Poisson regression was used to examine internal dose-response relationships, while controlling for important lifestyle factors and other agricultural exposures. Two metrics of exposure (lifetime days and intensity-weighted lifetime days) were used in exposure-response analyses with non-exposed applicators, as well as applicators in the lowest tertile of exposure, as reference groups. Incident cancers were identified through state tumor registries from enrollment in 1993 through 2002. Trifluralin exposure was not associated with cancer incidence overall among 51% of private and commercial applicators (n=25,712) who had used trifluralin. However, there was an excess of colon cancer in the exposure category of higher half of highest tertile (rate ratios (RR) of 1.76 (95% CI=1.05-2.95) using the non-exposed as a referent and 1.93 (95% CI=1.08-3.45) using those with the lowest tertile of exposure as the referent). There was also a non-significantly elevated risk for kidney cancer and bladder cancer in the highest exposure group, although only the kidney cancer finding was consistent across exposure metrics. Although there was a possible link between trifluralin exposure and colon cancer, small numbers and inconsistencies in dose response and subgroup analyses indicate that this may be a chance finding.

Inverse association between physical activity and colon cancer is well established, at least in men. We investigated the association of occupational physical activity with subsite-specific colorectal cancer risk. On the basis of occupational titles from the Swedish nationwide censuses in 1960 and 1970, we defined a cohort of women and men with the same work-related physical demands in 1960 and 1970. Incidence of colon and rectum cancer during 1971-1989 was ascertained through linkages to the Cancer Register. Relative risks (RRs) were estimated through Poisson regression. The risk for colon cancer increased with decreasing occupational physical activity. RR among sedentary women and men was 1.2 and 1.3 (P for trend=0.08 and

Introduction—A total of 74,942 female subjects were recruited in a population-based cohort study in Shanghai, China between 1997 and 2000. We examined the relationship between occupation and breast cancer risk by using baseline data from the cohort study. Methods—Cases were 586 women previously diagnosed with breast cancer at baseline and 438 women newly diagnosed with breast cancer by December 2004 during follow-up. Eight controls were randomly selected for each case from cancer-free cohort members and frequency-matched to the cases by year of birth and age at diagnosis, respectively. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk associated with occupations adjusting for typical breast cancer risk factors. Results—In the prevalent breast cancer data analysis, increased risks of breast cancer were associated with technicians in engineering/agriculture/forestry (OR= 1.6, 1.0-2.4), teaching personnel (OR=1.5, 1.1-2.0), tailoring/sewing workers (OR=1.6, 1.0-2.7), examiners/measurers/ testers (OR=1.5, 1.1-2.1) among those who started the jobs at least 20 years ago. In the incident cases, the significantly increased risks were associated with medical/health care workers (OR=1.4, 1.0-2.0), administrative clerical workers (OR=1.5, 1.0-2.4), postal/telecommunication workers (OR=2.2, 1.0-5.5), and odd-job workers (OR=1.7, 1.1-2.8) among those who started the jobs at least 20 years ago. The excess risks were found in both prevalent and incident cases for postal/telecommunication workers and purchasing/marketing personnel, although ORs reached only marginal significance. Conclusions—This study suggests that white-collar professionals and several production occupations may be associated with an increased risk of breast cancer.

Objective: To examine the association between occupation and chronic bronchitis among a cross section of Chinese women who participated in the Shanghai Women's Health Study. Methods: Cases were 4873 women who self-reported a physician-diagnosed bronchitis during adulthood. Controls were 9746 women randomly selected from Shanghai Women's Health Study participants and matched with the cases by year of birth and age at diagnosis. Lifetime occupational histories were obtained. Logistic regressions were used to evaluate the association between chronic bronchitis and occupation, adjusting for smoking, education, family income, and concurrent asthma. Results: We observed excess prevalence of bronchitis for textile occupation (odds ratio, OR = 1.09; 95% CI= 1.00-1.18) and industry (OR = 1.11; 95% CI = 1.03-1.19), welders (OR = 1.40; 95% CI= 1.01-1.92), packing and baling workers (OR = 1.39; 95% CI = 1.15-1.68), and warehousing industry (OR = 1.58; 95% CI = 1.08-2.30) We also identified several new associations that may warrant further exploration and confirmation, including employment in some metal fabrication industries, postal and telecommunication industry, and a few white-collar occupations and industries. Conclusions: Our study indicates that the risk of chronic bronchitis among women may be increased in some occupations and industries.

Objectives: Air pollution has been associated with an increased risk for lung cancer. We examined whether long-term air pollution is associated with bladder cancer risk. Methods: Information from a case-control study in Spain that included 1219 incident cases and 1271 hospital controls was used. Information on residential history including several indicators of exposure to air pollution and other potential risk factors was collected in a face-to-face computerised personal interview. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, smoking, occupation, water contaminants and diet. Results: Living more than 40 years in a city with a population of more than 100 000 was associated with an increased risk for bladder cancer overall (OR 1.30, 95% CI 1.04 to 1.63). Emissions of polycyclic aromatic hydrocarbons and diesel from industries near the residence, as evaluated by experts, were associated with an increased risk (OR 1.29, 95% CI 0.85 to 1.98), while lower or no excess risks were observed for other pollution-related variables. Odds ratios among never smokers tended to be higher than among smokers. Conclusions: The small to moderate positive associations found for several indices of air pollution and bladder cancer, while suggestive of excess risk, require further evaluation in other settings.

Background Findings on water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case–control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk. Objectives We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case–control study in Spain. Methods A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders. Results Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62; 95% confidence interval (CI), 0.40–0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33–0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13). Conclusion Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level.

The relationship between family history of cancer in first-degree relatives and risk of bladder cancer was examined in the Spanish Bladder Cancer Study. Information on family history of cancer was obtained for 1,158 newly diagnosed bladder cancer cases and 1,244 controls included in 18 hospitals between 1998 and 2001. A total of 464 (40.1%) cases and 436 (35.1%) controls reported a family history of cancer in ≥1 relative [odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.11-1.59]; the OR was 1.23 (95% CI, 1.01-1.50) among those with only one relative affected and 1.67 (95% CI, 1.23-2.29) among those with ≥2 affected relatives (Ptrend = 0.0004). A greater risk of bladder cancer was observed among those diagnosed at age ≤45 years (OR, 2.67; 95% CI, 1.10-6.50) compared with those diagnosed over age 45 years (OR, 1.27; 95% CI, 1.06-1.52). The OR of bladder cancer among subjects reporting a family history of cancer of the bladder was 2.34 (95% CI, 0.95-5.77). Statistically significant associations emerged between bladder cancer risk and family history of cancer of the esophagus, lung, prostate, and brain. The OR of bladder cancer for those reporting family history of bladder cancer was 4.76 (95% CI, 1.25-18.09) among NAT2-slow acetylators and 1.17 (95% CI, 0.17-7.86) among NAT2-rapid/intermediate acetylators (Pinteraction = 0.609). Among individuals with GSTM1 null and present genotypes, the corresponding ORs were 2.91 (95% CI, 0.44-19.09) and 4.21 (95% CI, 1.26-14.14), respectively (Pinteraction = 0.712). Limitations of our study are small sample size in subgroup analyses, reliability of family history data, and possible residual confounding by shared environmental exposures. Overall, our findings support the hypothesis that genetic factors play a role in bladder cancer etiology. Whether these correspond to low-penetrance cancer-predisposing polymorphisms acting together and/or interacting with environmental factors warrants further research. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1595–600)

The double-strand break DNA repair (DSBR) pathway is implicated in maintaining genomic stability and therefore could affect bladder cancer risk. Here we present data evaluating 39 single-nucleotide polymorphisms (SNPs) in seven candidate genes whose products are involved in DNA break sensing (NBS1, BRCA1 interacting genes BRIP1 and ZNF350), non-homologous end-joining (NHEJ) DNA repair (XRCC4) and homologous recombination (HR) repair (RAD51, XRCC2 and XRCC3). SNPs for RAD51 and XRCC2 covered most of the common variation. Associations with bladder cancer risk were evaluated in 1,150 newly diagnosed cases of urinary bladder transitional cell carcinomas and 1,149 controls conducted in Spain during 1997-2001. We found that the genetic variants evaluated significantly contributed to bladder cancer risk (global likelihood ratio test P = 0.01). Subjects with the ZNF350 R501S (rs2,278,415) variant allele showed significantly reduced risk compared with common homozygote variants, odds ratio (OR) [95% confidence interval (95% CI)]: 0.76 (0.62-0.93) per variant allele. Carriers of a putative functional SNP in intron 7 of XRCC4 (rs1,805,377) had significantly increased bladder cancer risk compared with common homozygotes: 1.33 (1.08-1.64) per variant allele. Lastly, XRCC2 homozygote variants for three promoter SNPs (rs10,234,749, rs6,464,268, rs3,218,373) and one non-synonymous SNP (rs3,218,536, R188H) were associated with reduced bladder cancer risk (ORs ranging from 0.36 to 0.50 compared with common homozygotes). Meta-analysis for XRCC3 T241M (rs861,539) had a significant small increase in risk among homozygote variants: OR (95% CI) = 1.17 (1.00-1.36). Results from this study provide evidence for associations between variants in genes in the DSBR pathway and bladder cancers risk that warrant replication in other study populations.

Organochlorine (OC) insecticides have been regulated as possible human carcinogens primarily on the basis of animal studies. However, the epidemiologic evidence is inconsistent. We investigated the relationship between cancer incidence and OC insecticide use among pesticide applicators enrolled in the Agricultural Health Study, a prospective cohort study of 57,311 licensed applicators in Iowa and North Carolina enrolled between 1993 and 1997. Information on ever use of seven organochlorine insecticides (aldrin, chlordane, DDT, dieldrin, heptachlor, lindane, toxaphene) was collected from a self-administered questionnaire at enrollment. Lifetime exposure-days to OC insecticides were calculated using additional data from a take-home questionnaire completed by 25,291 participants (44% of total). We found no clear evidence of an association between use of OC insecticides and incident cancers (N=1,150) ascertained through December, 2002. When we focused on individual insecticides and structurally similar groups (aldrin and dieldrin; chlordane and heptachlor), significantly increased relative risks of some cancers were observed for use of some chemicals (rectal cancer and chlordane, lung cancer and dieldrin, non-Hodgkin lymphoma (NHL) and lindane, melanoma and toxaphene, leukemia and chlordane / heptachlor). Some significant decreased relative risks were also observed (colon cancer and aldrin; overall cancer and heptachlor). In Conclusion, we did not observe any clear relationship between cancer risk and the use of OC insecticides. Our chemical-specific findings are based on small numbers and multiple comparisons, and should be interpreted with caution; however, some observed associations (lindane and NHL, chlordane/heptachlor and leukemia) are supported by previous evidence.

Background: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in drug-metabolizing genes. Methods: We analyzed personal interview data from 958 incident bladder cancer cases and 1,029 hospital controls from a multicenter case-control study in Spain. A drug matrix was developed to estimate cumulative lifetime dose of active ingredients. Polymorphisms in GSTP1, SULT1A1, CYP2E1, CYP2C9, and NAT2 were examined. Results: A significant reduction in bladder cancer risk [adjusted odds ratio (OR), 0.4; 95% confidence interval (95% CI), 0.2-0.9] was observed for regular users of nonaspirin NSAIDs compared with never users. Regular users of aspirin experienced no reduction in risk (OR, 1.0; 95% CI, 0.7-1.5). Regular users of paracetamol had no overall increased risk of bladder cancer (OR, 0.8; 95% CI, 0.4-1.3), but our data suggested a qualitative interaction with the GSTP1 I105V genotype. Subjects with at least one copy of the 359L or 144C variant alleles in the NSAID-metabolizing gene CYP2C9 had a slightly decreased risk of bladder cancer (OR, 0.8; 95% CI, 0.7-1.0; P = 0.037); however, having at least one copy of the 359L or 144C variant alleles did not significantly modify the protective effect of nonaspirin NSAID use. Conclusion: Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene CYP2C9. We found no evidence of an overall effect for paracetamol or aspirin use. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1696–703)

Background Cyanazine is a common pesticide used frequently in the United States during the 1980s and 1990s. Animal and human studies have suggested that triazines may be carcinogenic, but results have been mixed. We evaluated cancer incidence in cyanazine-exposed pesticide applicators among the 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS). Methods We obtained detailed pesticide exposure information from a self-administered questionnaire completed at enrollment (1993–1997). Cancer incidence was followed through January 2002. Over half of cyanazine-exposed applicators had ≥ 6 years of exposure at enrollment, and approximately 85% had begun using cyanazine before the 1990s. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple cancer sites among cyanazine-exposed applicators. We calculated ptrend values, and all statistical tests were two-sided. Two exposure metrics were used: tertiles of lifetime days of exposure (LD) and intensity-weighted LD. Results A total of 20,824 cancer-free AHS applicators reported ever using cyanazine at enrollment. Cancer incidence comparisons between applicators with the lowest cyanazine exposure and those with the highest exposure yielded the following for the LD metric: all cancers, RR = 0.99 (95% CI, 0.80–1.24); prostate cancer, RR = 1.23 (95% CI, 0.87–1.70); all lymphohematopoietic cancers, RR = 0.92 (95% CI, 0.50–1.72); non-Hodgkin lymphoma, RR = 1.25 (95% CI, 0.47–3.35); lung cancer, RR = 0.52 (95% CI, 0.22–1.25). Conclusions We did not find any clear, consistent associations between cyanazine exposure and any cancer analyzed. The number of sites was small for certain cancers, limiting any conclusion with regard to ovarian, breast, and some other cancers.

We examined the effects of dose, type of tobacco, cessation, inhalation, and environmental tobacco smoke exposure on bladder cancer risk among 1,219 patients with newly diagnosed bladder cancer and 1,271 controls recruited from 18 hospitals in Spain. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between bladder cancer risk and various characteristics of cigarette smoking. Current smokers (men: OR, 7.4; 95% CI, 5.3-10.4; women: OR, 5.1; 95% CI, 1.6-16.4) and former smokers (men: OR, 3.8; 95% CI, 2.8-5.3; women: OR, 1.8; 95% CI, 0.5-7.2) had significantly increased risks of bladder cancer compared with nonsmokers. We observed a significant positive trend in risk with increasing duration and amount smoked. After adjustment for duration, risk was only 40% higher in smokers of black tobacco than that in smokers of blond tobacco (OR, 1.4; 95% CI, 0.98-2.0). Compared with risk in current smokers, a significant inverse trend in risk with increasing time since quitting smoking blond tobacco was observed (≥20 years cessation: OR, 0.2; 95% CI, 0.1-0.9). No trend in risk with cessation of smoking black tobacco was apparent. Compared with men who inhaled into the mouth, risk increased for men who inhaled into the throat (OR, 1.7; 95% CI, 1.1-2.6) and chest (OR, 1.5; 95% CI, 1.1-2.1). Cumulative occupational exposure to environmental tobacco smoke seemed to confer increased risk among female nonsmokers but not among male nonsmokers. After eliminating the effect of cigarette smoking on bladder cancer risk in our study population, the male-to-female incidence ratio decreased from 8.2 to 1.7, suggesting that nearly the entire male excess of bladder cancer observed in Spain is explained by cigarette smoking rather than occupational/environmental exposures to other bladder carcinogens. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1348–54)

Cancer epidemiologyCancer type: cancerStudy design: prospective cohortStudy size: 9089 exposed, 15285 non-exposedDescription of cohort(s) studied: Exposure(s) evaluated: pendimethelinImpact on risk: The risk for colorectal cancer was not associated with increasingpendimethalin exposure (for the highest exposed subjects, RR = 1.0; 95% CI = 0.3-3.4 when using the nonexposed as the referent group, or RR = 1.0; 0.2-4.4 when using the low-exposed as the referent group)Elevated risk of rectal cancer among subjects with the highest lifetime pendimethalin exposure-days compared with the nonexposed group (4.3; 1.5- 12.7)An increased risk for rectal cancer was found comparing subjects in the highest tertile with the non-pendimethalin exposed applicators (RR = 3.6; 95% CI = 1.2-11.3; P for trend = 0.02), whereas no clear pattern of RRs was observed when using the low-exposed group as the referent (2.9; 0.5-16.7; P for trend = 0.23).KEYWORDS CLASSIFICATION: analysis;Adult;Aniline Compounds;cancer epidemiology;Cohort Studies;epidemiology;Environmental Exposure;Female;Humans;Iowa;Male;Middle Aged;Neoplasms;North Carolina;poisoning;Prospective Studies;Questionnaires;Research;trends. BACKGROUND: Pendimethalin, a widely used herbicide, has been classified as a group C possible human carcinogen by the U.S. Environmental Protection Agency. We evaluated the incidence of cancer in relation to reported pendimethelin use among pesticide applicators in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. METHODS: Information on pesticide use came from two questionnaires (enrollment and take-home). The present analysis includes 9089 pendimethalin-exposed and 15,285 nonpendimethalin-exposed pesticide applicators with complete information on pendimethalin use and covariates from a take-home questionnaire. We conducted Poisson regression analyses to evaluate the association of pendimethalin exposure with cancer incidence (mean follow-up = 7.5 years) using two exposure metrics: tertiles of lifetime days of exposure and tertiles of intensity-weighted lifetime days of exposure. RESULTS: Overall cancer incidence did not increase with increasing lifetime pendimethalin use, and there was no clear evidence of an association between pendimethalin use and risks for specific cancers. The risk for rectal cancer rose with increasing lifetime pendimethalin exposure when using nonexposed as the reference (rate ratio = 4.3; 95% confidence interval = 1.5-12.7 for the highest exposed subjects; P for trend = 0.007), but the association was attenuated when using the low exposed as the referent group (P for trend = 0.08). Similar patterns for rectal cancer were observed when using intensity-weighted exposure-days. The number of rectal cancer cases among the pendimethalin-exposed was small (n = 19). There was some evidence for an elevated risk for lung cancer, but the excess occurred only in the highest exposure category for lifetime pendimethalin exposure. The trends for lung cancer risk were inconsistent for different exposure metrics. CONCLUSIONS: We did not find a clear association of lifetime pendimethalin exposure either with overall cancer incidence or with specific cancer sites.

This study was carried out to examine the association between pesticide exposure and lung cancer mortality. We conducted an autopsy based case-control study in Leningrad Province in Russia. A total of 540 lung cancer cases and 582 controls were identified among subjects who had died in the hospitals of the Leningrad province between 1993 and 1998. Using work history records, we assessed exposure to pesticide at the level of industry and job title. Unconditional logistic regression was used to calculate adjusted odds ratio for pesticide exposure and lung cancer mortality. There was no association between ever exposure to pesticide and lung cancer mortality overall (odds ratio=1.06, 95% confidence interval=0.82–1.36) and in both men (odds ratio=1.11, 95% confidence interval=0.84–1.46) and women (odds ratio=0.74, 95% confidence interval=0.37–1.46). We observed no statistically significant odds ratio by duration of pesticide exposure, intensity of pesticide exposure, and cumulative pesticide exposures with lung cancer mortality in both smokers and nonsmokers. Odds ratio also did not differ when the analysis was restricted to individuals who had exposure data with high confidence scores. Our findings suggest no associations between pesticide exposures and mortality of lung cancer in the population of the Leningrad province in Russia that deserves further evaluation. Keywords: Lung neoplasms, Occupation, Pesticide exposure, Russia

Nucleotide excision repair (NER) is critical for protecting against damage from carcinogens in tobacco smoke. We evaluated the influence of common genetic variation in the NER pathway on bladder cancer risk by analyzing 22 single nucleotide polymorphisms (SNP) in seven NER genes (XPC, RAD23B, ERCC1, ERCC2, ERCC4, ERCC5, and ERCC6). Our study population included 1,150 patients with transitional cell carcinoma of the urinary bladder and 1,149 control subjects from Spain. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, and smoking status. Subjects with the variant genotypes for SNPs in four of the seven genes evaluated had small increases in bladder cancer risk compared to subjects with the homozygous wild-type genotypes: RAD23B IVS5-15A>G (OR, 1.3; 95% CI, 1.1-1.5; P = 0.01), ERCC2 R156R (OR, 1.3; 95% CI, 1.1-1.6; P = 0.006), ERCC1 IVS5+33A>C (OR, 1.2; 95% CI, 1.0-1.5; P = 0.06; Ptrend = 0.04), and ERCC5 M254V (OR, 1.4; 95% CI, 1.0-2.0; P = 0.04). A global test for pathway effects indicated that genetic variation in NER characterized by the 22 SNPs analyzed in this study significantly predicts bladder cancer risk (P = 0.04). Pairwise comparisons suggested that carrying variants in two genes could result in substantial increases in risk. Classification tree analyses suggested the presence of subgroups of individuals defined by smoking and NER genotypes that could have substantial increases in risk. In conclusion, these findings provide support for the influence of genetic variation in NER on bladder cancer risk. A detailed characterization of genetic variation in key NER genes is warranted and might ultimately help identify multiple susceptibility variants that could be responsible for substantial joint increases in risk. (Cancer Epidemiol Biomarkers Prev 2006;15(3):536–42)

Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.

Objective: Several studies have evaluated the relationship between physical activity and lung cancer. To summarize and review these studies, we conducted a meta-analysis of all relevant reports published from 1966 through October 2003. Method: Adjusted odds ratios (ORs) from the original studies were pooled by the inverse of their variance, and all pooled estimates were accompanied by an assessment of heterogeneity across investigations. Test for linear trend across activity categories (low, moderate, high) were applied. Results: The combined ORs were 0.87 (95 confidence interval=0.79–0.95) for moderate leisure-time physical activity (LPA) and 0.70 (0.62–0.79) for high activity (ptrend = 0.00). This inverse association occurred for both sexes, although it was somewhat stronger for women. No evidence of publication bias was found. Several studies were able to adjust for smoking, but none adjusted for possible confounding from previous malignant respiratory disease. Our simulations suggest that this condition is unlikely to entirely explain the inverse association. Conclusion: The findings of this meta-analysis indicate that higher levels of LPA protect against lung cancer. The inverse association is possible remains confounded by inadequately controlled smoking patterns. However on the whole, confounding seems an unlikely explanation for the findings of individual studies on non-smokers.

Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993-1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or "cumulative exposure days" (years of use times days/year); and c) intensity-weighted cumulative exposure days (years of use times days/year times estimated intensity level). Poisson regression was used to estimate exposure-response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers.

Background: Chlorpyrifos is one of the most widely used insecticides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Methods: A total of 54 383 pesticide applicators were included in this analysis. Detailed information on pesticide exposure and lifestyle factors was obtained from selfadministered questionnaires completed at the time of enrollment (December 1993‐December 1997). Poisson regression analysis was used to evaluate the association between chlorpyrifos exposure and cancer incidence after adjustment for potential confounders. All statistical tests were two-sided. Results: A total of 2070 incident malignant neoplasms were diagnosed through 2001. The rate ratio for all cancers combined among chlorpyrifos-exposed applicators compared with nonexposed applicators was 0.97 (95% confidence interval 0.87 to 1.08). For most cancers analyzed, there was no evidence of an exposure‐response relationship. However, the incidence of lung cancer was statistically significantly associated with both chlorpyrifos lifetime exposure-days (Ptrend .002) and chlorpyrifos intensity-weighted exposuredays (Ptrend .036). After adjustment for other pesticide exposures and demographic factors, individuals in the highest quartile of chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer 2.18 (95% confidence interval 1.31 to 3.64) times that of those with no chlorpyrifos exposure. Conclusion: Our findings suggest an association between chlorpyrifos use and incidence of lung cancer that deserves further evaluation. [J Natl Cancer Inst 2004;96:1781‐9]

Atrazine is the most heavily applied agricultural pesticide for crop production in the United States. Both animal and human studies have suggested that atrazine is possibly carcinogenic, but results have been mixed. We evaluated cancer incidence in atrazine-exposed pesticide applicators among 53,943 participants in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.We obtained detailed pesticide exposure information using a self-administered questionnaire completed at the time of enrollment (1993-1997). Cancer incidence was followed through December 31, 2001. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple types of cancer among atrazine exposed applicators. P(trend) values were calculated using atrazine exposure as a continuous variable, and all statistical tests were two-sided. Two exposure metrics were used: quartiles of lifetime days of exposure and quartiles of intensity-weighted lifetime days of exposure.36,513 (68%) applicators reported ever using atrazine; exposure was not associated with overall cancer incidence. Comparisons of cancer incidence in applicators with the highest atrazine exposure and those with the lowest exposure, assessed by lifetime days (RR(LD)) and intensity-weighted lifetime days (RR(IWLD)) of exposure yielded the following results: prostate cancer, RR(LD) = 0.88, 95% CI = 0.63 to 1.23, P(trend) =.26, and RR(IWLD) = 0.89, 95% CI = 0.63 to 1.25, P(trend) =.35; lung cancer, RR(LD) = 1.91, 95% CI = 0.93 to 3.94, P(trend) =.08, and RR(IWLD) = 1.37, 95% CI = 0.65 to 2.86, P(trend) =.19; bladder cancer, RR(LD) = 3.06, 95% CI = 0.86 to 10.81, P(trend) =.18, and RR(IWLD) = 0.85, 95% CI = 0.24 to 2.94, P(trend) =.71; non-Hodgkin lymphoma, RR(LD) = 1.61, 95% CI = 0.62 to 4.16, P(trend) =.35, and RR(IWLD) = 1.75, 95% CI = 0.73 to 4.20, P(trend) =.14; and multiple myeloma, RR(LD) = 1.60, 95% CI = 0.37 to 7.01, P(trend) =.41, and RR(IWLD) = 2.17, 95% CI = 0.45 to 10.32, P(trend) =.21.Our analyses did not find any clear associations between atrazine exposure and any cancer analyzed. However, further studies are warranted for tumor types in which there was a suggestion of trend (lung, bladder, non-Hodgkin lymphoma, and multiple myeloma).

The authors examined the relation between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohort study of 55,332 male pesticide applicators from Iowa and North Carolina with no prior history of prostate cancer. Data were collected by means of self-administered questionnaires completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 1999. A prostate cancer standardized incidence ratio was computed for the cohort. Odds ratios were computed for individual pesticides and for pesticide use patterns identified by means of factor analysis. A prostate cancer standardized incidence ratio of 1.14 (95% confidence interval: 1.05, 1.24) was observed for the Agricultural Health Study cohort. Use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Important family history-pesticide interactions were observed.

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.

Objective: To investigate the risk of cancer among veterinarians in a large record-linkage study from Sweden. Methods: We used the nationwide, Swedish Cancer Environment Registry III, which links the Cancer Register data for 1971–1989 to the national population censuses from 1960 and 1970, to compare the incidence of cancer among male veterinarians to that of the remaining part of the active population using multivariable Poisson regression models and standardized incidence ratios. One thousand one hundred and seventy eight men classified as veterinarians or workers in the veterinary industry at either census were identified. Results: Veterinarians in the veterinary industry experienced increased risk of esophageal (relative risk (RR) 3.78, 95% confidence interval (CI) 1.42–10.09), colon (RR: 2.36, 95% CI: 1.42–3.91), pancreatic (RR: 2.10, 95% CI: 0.94–4.68) and brain (RR: 2.51, 95% CI: 1.04–6.03) cancers as well as melanoma of the skin (RR: 2.77, 95% CI: 1.24–6.17). Similar excess risks were observed when veterinarians were compared with individuals of similar socio-economic status. Conclusion: The increased risks of esophageal, colon, pancreatic and brain cancers as well as melanoma observed among veterinarians did not seem to be explained by the high socio-economic status of this occupational group. Therefore, it is possible that some of these results reflect the carcinogenicity of occupational exposures, including animal viruses, solar or ionizing radiations and anesthetics.

Exposures to multiple chemical, physical, and biological agents in agricultural work environments can result in confounding that may obscure or distort risks observed in epidemiologic studies. The Agricultural Health Study (AHS) is a large epidemiology study being conducted to investigate health risks among pesticide applicators and their families. During enrollment in the AHS, questionnaires were administered to over 52,000 licensed pesticide applicators from North Carolina and Iowa, who were mostly farmers. Questions about the frequency of various farming tasks were used to estimate the prevalence of exposure to solvents (25%), metals (68%), grain dusts (65%), diesel exhaust fumes (93%), and other hazards, including exposure to pesticides. Most of the farmers in the AHS reported performing routine maintenance tasks at least once a month, such as painting (63%), welding (64%), and repair of pesticide equipment (58%). The majority of farmers (74% in North Carolina; 59% in Iowa) reported holding nonfarm jobs, of which the most frequent were construction and transportation. The majority of the farmers enrolled in the AHS (55%) also reported that they mixed or applied pesticides on 10 or more days per year. The associations between the use of pesticides and the frequency with which the farmers in the AHS reported performing various types of specific farming activities were assessed to evaluate potential confounding. Confounding risk ratios calculated for these activities suggest that the magnitude of bias due to confounding is likely to be minimal.

Objectives A hospital-based case-referent study was conducted to identify occupational risk factors for laryngeal cancer. In a previous report an association was found between laryngeal cancer and occupations with potential dust exposure; a job-exposure matrix was developed to aid further evaluation of laryngeal cancer risks from five occupational dust exposures. Methods Among 7631 cancer cases from the Okmeydani Hospital, Istanbul, between 1979 and 1984, 958 larynx cancer cases were identified among men. After exclusions, 940 laryngeal cancer cases and 1519 referents were available. A standardized questionnaire was used to obtain basic information on the patients. Seven-digit standard occupational and industrial codes were created to classify the job and industrial titles. A job-exposure matrix was developed for occupational dusts, including silica, asbestos, wood, cotton, and grain, and age-, smoking-, and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate risks of laryngeal cancer. Results An excess of laryngeal cancer occurred for workers potentially exposed to silica and cotton dust, particularly for supraglottic cancer (OR 1.8, 95% CI 1.3-2.3, for silica and OR 1.6, 95% CI 1.1-2.5, for cotton dust), and there was a significant dose-response relationship with silica exposure. No relationship was found between laryngeal cancer and asbestos, grain, or wood dust exposures. Conclusions Laryngeal cancer, especially supraglottic tumors, is associated with silica and cotton dust exposures in Turkey.

Repeat interviews from 4,088 Iowa pesticide applicators participating in the Agricultural Health Study provided the opportunity to evaluate the reliability of self-reported information on pesticide use and various demographic and life-style factors. Self-completed questionnaires were administered 1 year apart when participants returned to county agricultural extension offices for pesticide certification or training. Percentage agreement for ever-/never-use of specific pesticides and application practices was quite high, generally ranging from 70% to more than 90%, and did not vary by age, educational level, or farm size. Agreement was lower (typically 50-60%) for duration, frequency, or decade of first use of specific pesticides. Level of agreement regarding pesticide use in this population is similar to that generally found for factors typically used in epidemiologic studies such as tobacco use and higher than typically reported for diet, physical activity, and medical conditions.

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

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% CI 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.

Background Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. Methods In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. Results Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. Conclusions Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

Urinary benzene (UB) was investigated as a biomarker of exposure among benzene-exposed workers and unexposed subjects in Shanghai, China. Measurements were performed via headspace solid phase microextraction of 0.5 ml of urine specimens followed by gas chromatography-mass spectrometry. This assay is simple and more sensitive than other methods (detection limit 0.016 microg benzene/l urine). The median daily benzene exposure was 31 p.p.m. (range 1.65-329 p.p.m.). When subjects were divided into controls (n = 41), those exposed toor =31 p.p.m. benzene (n = 22) and31 p.p.m. benzene (n = 20), the median UB levels were 0.069, 4.95 and 46.1 microg/l, respectively (Spearman r = 0.879, P0.0001). A linear relationship was observed between the logarithm of UB and the logarithm of benzene exposure in exposed subjects according to the following equation: ln(UB, microg/l) = 0.196 + 0.709 ln (exposure, p.p.m.) (r = 0.717, P0.0001). Considering all subjects, linear relationships were also observed between the logarithm of UB and the corresponding logarithms of four urinary metabolites of benzene, namely t,t-muconic acid (r = 0.938, P0.0001), phenol (r = 0.826, P0.0001), catechol (r = 0.812, P0.0001) and hydroquinone (r = 0.898, P:0.0001). Ratios of individual metabolite levels to total metabolites versus UB provide evidence of competitive inhibition of CYP450 enzymes leading to increased production of phenol and catechol at the expense of hydroquinone and muconic acid. Among control subjects UB was readily detected with a mean level of 0.145 microg/l (range 0.027-2.06 microg/l), compared with 5.63 microg/l (range 0.837-26.38 microg/l) in workers exposed to benzene below 10 p.p.m. (P0.0001). This suggests that UB is a good biomarker for exposure to low levels of benzene.

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.

Objective: To investigate the risk of cancer among workers exposed to diesel emissions in a large record-linkage study from Sweden. Methods: The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971–1989, by occupation and industry of employment as reported in the 1960 and 1970 censuses. After excluding farmers, we classified job and industry titles according to estimated probability and intensity of exposure to diesel emissions. Exposed men in the 1960 census contributed over 7,400,000 person-years, and exposed women contributed over 240,000. We compared them to the remainder of the employed population, using indirect standardization and multivariate Poisson regression analysis. Results: Men exposed in the 1960 census experienced an increased risk of lung cancer: the relative risks (RRs) were 0.95 (95% confidence interval [CI] 0.9–1.0), 1.1 (1.1–1.2) and 1.3 (1.3–1.4) for low, medium, and high intensity of exposure. Corresponding results for probability of exposure were 1.1 (1.0–1.1), 0.9 (0.86–0.94) and 1.2 (1.1–1.2). The risk was higher for squamous cell carcinoma of the lung than for other histological types. Results in women were not suggestive of an effect (RR in the category of medium or high intensity of exposure 1.1, 95% CI 0.6–1.8). A small but significant increase in risk of cancers of the stomach (SIR 1.06), pancreas (SIR 1.05), larynx (SIR 1.09), and the kidney (SIR 1.06) was present among men exposed to diesel emissions, without a clear trend according to either probability or intensity of exposure. The SIR among women was non-significantly increased for stomach, pancreatic, and laryngeal cancers, but not for kidney cancer. Furthermore, a significantly increased risk of oral/pharyngeal (SIR 1.64) and cervical (SIR 1.48) cancers was present among women, with a suggestion of a dose–response relationship. There was no increased risk of bladder cancer in either gender. Conclusions: The results of this study provide evidence of a positive exposure–response relationship between exposure to diesel emissions and lung cancer risk among men. The positive results for other neoplasms, such as stomach, pancreatic, oral/pharyngeal, and cervical cancers, cannot be attributed to diesel exposure, but they deserve attention in future investigations.

Indirect evidence, notably ecological comparisons and an association with skin cancer, links non-Hodgkin's lymphoma (NHL) with exposure to sunlight. We conducted a population-based, nationwide cohort study with exposure to outdoor work inferred from job titles reported in the population and housing censuses in 1960 and/or 1970 and by classifying each individual's work and home addresses according to latitude. Follow-up for cancer incidence was accomplished through record linkages with the virtually complete Swedish Cancer Registry. The cohort included all Swedish residents who were recorded as gainfully employed in both censuses. Altogether 4,171,175 individuals contributing 69,639,237 person-years accrued through 1989 were included in the analyses. We identified 10,381 cases of NHL, 4,018 cases of chronic lymphocytic leukemia (CLL), 11,398 cases of malignant melanoma (MM) and 11,913 cases of squamous cell skin cancer (SCC). We calculated age-adjusted relative risks for NHL, CLL, MM and SCC in strata based on estimated residential and occupational sunlight exposure. Interaction effects were considered for pesticide and solvent exposure. NHL, MM and SCC, but not CLL, were positively associated with increasingly southerly residential latitude, with stronger associations seen for skin cancer compared to NHL. Occupational sun exposure was not associated with the risk of developing any of the studied cancers. Pesticides and solvents also were not related to an increased risk of NHL, nor did these exposures enhance effects of residential or occupational sunlight exposure. Our results provide some support for an association of sunlight exposure with NHL incidence based on the associations seen using geographic latitude of residence as a proxy for exposure. Although type of occupation may be an imperfect index of the biologically relevant ultraviolet (UV) light dose, our data on individual exposure are not consistent with an important role of sunlight in the etiology of NHL.

Objective: Our purpose was to investigate effects of physical activity on risk for breast cancer.

Objective The primary objective was to determine whether occupational exposure to organic solvents is related to an increased risk of systemic sclerosis (SSc; scleroderma). Methods Occupational histories were obtained from 178 SSc patients and 200 controls. Exposure scores were computed for each individual using job exposure matrices, which were validated by an industrial expert. Results Among men, those with SSc were more likely than controls to have a high cumulative intensity score (odds ratio [OR] 2.9, 95% confidence interval [95% CI] 1.1-7.6) and a high maximum intensity score (OR 2.9, 95% CI 1.2-7.1) for any solvent exposure. They were also more likely than controls to have a high maximum intensity score for trichloroethylene exposure (OR 3.3, 95% CI 1.0-10.3). Among men and women, significant solvent-disease associations were observed among SSc patients who tested positive for the anti-Scl-70 autoantibody; these trends were not observed among the men and women who tested negative for anti-Scl-70. Conclusion These results provide evidence that occupational solvent exposure may be associated with an increased risk of SSc.

The role of occupational substances as stomach carcinogens has not been well investigated. In 1979, a population-based case-control study was undertaken in Montreal to explore the possible association between hundreds of occupational circumstances and several cancer sites, including the stomach. In total, 250 male patients with pathologically confirmed stomach cancer, 2,289 male controls with cancers at other sites, and 533 population-based male controls were interviewed to obtain detailed job histories and relevant data on potential confounders. Job histories were evaluated by expert chemists and hygienists and translated into a history of occupational exposures. On the basis of results of preliminary analyses and literature review, we selected 16 occupations and industries and 32 substances for in-depth multivariate analysis using the pooled group of cancer and population controls. We found elevated risks for excavators and pavers, forestry workers, electric and electronic workers, motor transport workers, and food industry employees. The substances that were most plausibly associated with gastric cancer were: crystalline silica, leaded gasoline, grain dust, lead dust, zinc dust, hydraulic fluids, and glycol ethers. The paucity of data documenting the association between most of these occupational circumstances and gastric cancer precludes drawing firm conclusions.

Background: Benzene is a widely distributed environmental contaminant known to cause leukemia, particularly acute nonlymphocytic leukemia, and perhaps other hematologic neoplasms and disorders. Few epidemiologic studies, however, have been able to address relationships between the extent of benzene exposure and the level of risk. Purpose : A large cohort study was carried out in China to evaluate the risks of developing specific hematologic neoplasms and selected related disorders in relationship to quantitative estimates of occupational benzene exposure. Methods: A cohort of 74828 benzene-exposed and 35805 unexposed workers employed from 1972 through 1987 in 12 cities in China was identified and followed to determine the incidence of hematologic neoplasms and related disorders. Estimates of benzene exposure were derived from work histories and available historic benzene measurements. Existing pathologic material and supporting medical records were reviewed to establish diagnoses of disease. Relative risks (RRs) (i.e., ratios of incidence rates for specific hematologic neoplasms and related disorders in the benzene-exposed group to incidence rates in the unexposed group) were determined by use of Poisson regression analysis, with stratification by age and sex. Results: For workers historically exposed to benzene at average levels of less than 10 parts per million (ppm), the RR for all hematologic neoplasms combined was 2.2 (95% confidence interval [CI] = 1.1-4.2), and, for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes, the RR was 3.2 (95% CI = 1.0-10.1). For individuals who were occupationally exposed to benzene at constant levels of 25 ppm or more, the RR for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was 7.1 (95% CI = 2.1-23.7). Workers with 10 or more years of benzene exposure had an RR of developing non-Hodgkin's lymphoma of 4.2 (95% CI = 1.1-15.9), and the development of this neoplasm was linked most strongly to exposure that had occurred at least 10 years before diagnosis (i.e., distant exposure) (P for trend = .005, two-sided). In contrast, the risk for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was significantly increased among those with more recent benzene exposure (P for trend = .003, two-sided), but it was not linked to distant exposure (P for trend = .51, two-sided). Conclusions: The results of this study suggest that benzene exposure is associated with a spectrum of hematologic neoplasms and related disorders in humans. Risks for these conditions are elevated at average benzene-exposure levels of less than 10 ppm and show a tendency, although not a strong one, to rise with increasing levels of exposure. The temporal pattern of benzene exposure appears to be important in determining the risk of developing specific diseases.

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