Impact of pesticide exposure misclassification on estimates of relative risks in the Agricultural Health Study.

BACKGROUND: The Agricultural Health Study (AHS) is a prospective study of licensed pesticide applicators and their spouses in Iowa and North Carolina. We evaluate the impact of occupational pesticide exposure misclassification on relative risks using data from the cohort and the AHS Pesticide Exposure Study (AHS/PES). METHODS: We assessed the impact of exposure misclassification on relative risks using the range of correlation coefficients observed between measured post-application urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) and a chlorpyrifos metabolite and exposure estimates based on an algorithm from 83 AHS pesticide applications. RESULTS: Correlations between urinary levels of 2,4-D and a chlorpyrifos metabolite and algorithm estimated intensity scores were about 0.4 for 2,4-D (n=64), 0.8 for liquid chlorpyrifos (n=4) and 0.6 for granular chlorpyrifos (n=12). Correlations of urinary levels with kilograms of active ingredient used, duration of application, or number of acres treated were lower and ranged from -0.36 to 0.19. These findings indicate that a priori expert-derived algorithm scores were more closely related to measured urinary levels than individual exposure determinants evaluated here. Estimates of potential bias in relative risks based on the correlations from the AHS/PES indicate that non-differential misclassification of exposure using the algorithm would bias estimates towards the null, but less than that from individual exposure determinants. CONCLUSIONS: Although correlations between algorithm scores and urinary levels were quite good (ie, correlations between 0.4 and 0.8), exposure misclassification would still bias relative risk estimates in the AHS towards the null and diminish study power.

Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Job strain, hypoxia and risk of amyotrophic lateral sclerosis: Results from a death certificate study.

Amyotrophic lateral sclerosis (ALS) most likely results from a multifactorial gene-environment interaction. Strenuous physical activity and occupational exposures have been suggested to play a role, and an abnormal response to hypoxia has been proposed in ALS pathogenesis. To test the hypothesis of an excess risk in occupations typically leading to intermittent hypoxia at the tissue level, we accessed a large publicly available database, including death certificates from 24 U.S. states in 1984-1998. We conducted a case-control analysis of 14,628 deaths due to ALS therein reported and 58,512 controls deceased from other selected causes of death, frequency matched by age, gender and broad geographic area. ALS risk associated with physical activity, and occupations leading to intermittent hypoxia, such as fire fighters and professional athletes, were calculated with unconditional logistic regression, adjusting by age, marital status, residence, and socioeconomic status. Physical activity in general did not show an association with ALS risk. Risk associated with occupation as a professional athlete was elevated (OR = 1.81, 99% CI 0.69-4.78), but not significantly so. Fire fighters showed a significant two-fold excess ALS risk (OR = 2.0; 99% CI 1.2-3.2). Based on our findings and the current clinical, epidemiological and experimental evidence, we suggest that occupational conditions typically leading to intermittent hypoxia, such as fire fighting, might be an ALS risk factor in subjects genetically prone to an abnormal response to hypoxia.

Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.

Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs) in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5)). To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651) were associated with increased risk for bladder cancer: odds ratio (95% confidence interval): 2.52 (1.06-5.97), 2.74 (1.26-5.98), and 3.02 (1.36-6.63), respectively; and a polymorphism in intron 2 (rs3024994) was associated with reduced risk: 0.65 (0.46-0.91). Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively). These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.

TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis.

The transforming growth factor-beta (TGF-beta) 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-beta 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.

Occupational exposure to solvents and risk of non-Hodgkin lymphoma in Connecticut women.

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 < 0.01), cumulative intensity (P = 0.01), and cumulative probability (P < 0.01) level of organic solvent and with average probability level (P = 0.02) and cumulative intensity level of chlorinated solvent (P = 0.02). Analyses by NHL subtype showed a risk pattern for diffuse large B-cell lymphoma similar to that for overall NHL, with stronger evidence of an association with benzene exposure. Results suggest an increased risk of NHL associated with occupational exposure to organic solvents for women.

Determinants of quality of interview and impact on risk estimates in a case-control study of bladder cancer.

The authors evaluated potential determinants of the quality of the interview in a case-control study of bladder cancer and assessed the effect of the interview quality on the risk estimates. The analysis included 1,219 incident bladder cancer cases and 1,271 controls recruited in Spain in 1998-2001. Information on etiologic factors for bladder cancer was collected through personal interviews, which were scored as unsatisfactory, questionable, reliable, or high quality by the interviewers. Eight percent of the interviews were unsatisfactory or questionable. Increasing age, lower socioeconomic status, and poorer self-perceived health led to higher proportions of questionable or unreliable interviews. The odds ratio for cigarette smoking, the main risk factor for bladder cancer, was 6.18 (95% confidence interval: 4.56, 8.39) overall, 3.20 (95% confidence interval: 1.13, 9.04) among unsatisfactory or questionable interviews, 6.86 (95% confidence interval: 4.80, 9.82) among reliable interviews, and 7.70 (95% confidence interval: 3.64, 16.30) among high-quality interviews. Similar trends were observed for employment in high-risk occupations, drinking water containing elevated levels of trihalomethanes, and use of analgesics. Higher quality interviews led to stronger associations compared with risk estimation that did not take the quality of interview into account. The collection of quality of interview scores and the exclusion of unreliable interviews probably reduce misclassification of exposure in observational studies.

Occupational exposure to magnetic fields and the risk of brain tumors.

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 < or =1.5 mG, >1.5 to <3.0 mG, and > or =3.0 mG. Four exposure metrics were evaluated: (1) maximum exposed job; (2) total years of exposure >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 > or =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.

Coffee consumption, genetic susceptibility and bladder cancer risk.

OBJECTIVE: We evaluated the bladder cancer risk associated with coffee consumption in a case-control study in Spain and examined the gene-environment interactions for genetic variants of caffeine-metabolizing enzymes. METHODS: The analyses included 1,136 incident cases with urothelial carcinoma of the urinary bladder and 1,138 controls. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for area, age, gender, amount of cigarette smoking, and years since quitting among former smokers. RESULTS: The OR (95% CI) for ever consumed coffee was 1.25 (0.95-1.64). For consumers of 1, 2, 3, and 4 or more cups/day relative to never drinkers, OR were, respectively, 1.24 (0.92-1.66), 1.11 (95% CI 0.82-1.51), 1.57 (1.13-2.19), and 1.27 (0.88-1.81). Coffee consumption was higher in smokers compared to never smokers. The OR for drinking at least 4 cups/day was 1.13 (0.61-2.09) in current smokers, 1.57 (0.86-2.90) in former smokers, and 1.23 (0.55-2.76) in never smokers. Gene-coffee interactions evaluated in NAT2, CYP1A2, and CYP2E1-02 and CYP1A1 were not identified after adjusting for multiple testing. CONCLUSION: We observed a modest increased bladder cancer risk among coffee drinkers that may, in part, be explained by residual confounding by smoking. The findings from the gene-coffee interactions need replication in further studies.

Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case-control study.

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 <0.0001. The lowest cancer risk was noted in never smokers in the highest methylation quartile (never smokers in Q4). By comparison with never smokers in the highest quartile, current smokers in the lowest methylation quartile had the highest risk of bladder cancer (Q1: OR 25.51 [9.61-67.76], p for interaction 0.06). In analyses stratified by smoking, hypomethylation was a strong risk factor in never smokers (OR 6.39 [2.37-17.22]). Amount of methylation in controls were not associated with baseline characteristics, micronutrients, or selected genotypes in folate metabolism pathways. INTERPRETATION: For the first time, to our knowledge, we have shown in a large case-control study that leucocyte DNA hypomethylation is associated with increased risk of developing bladder cancer, and this association is independent of smoking and the other assessed risk factors. Amount of global methylation in genomic DNA could provide a useful biomarker of susceptibility to certain cancer types and further research is warranted.

Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes.

Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (approximately 90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk.

Does increased urination frequency protect against bladder cancer?

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.

Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study.

OBJECTIVE: Captan is a widely used antifungal pesticide whose potential to cause cancer in humans is uncertain. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Micronuclei assessment in the urothelial cells of women using hair dyes and its modulation by genetic polymorphisms.

Increases in the frequency of micronuclei (MN) in exposed cells can be used as a measure of genotoxicity. Hair dyes contain chemicals that are eliminated by urine and could be genotoxic to urothelial cells. To address this question, we evaluated whether hair dye use is associated with an increase in the frequency of MN in urothelial cells, and whether this association is modified by NAT1 (N-acetyltransferase 1), NAT2 (N-acetyltransferase 2) and GSTM1 (glutathione-S-transferase M1) genotypes. We included 92 women participating as controls in a bladder cancer case-control study in Spain. Of those, 72 had adequate number of cells to be included in the MN analysis. There were no significant differences in the mean MN frequency in women using hair dyes in the last month (9.88 MN/1000 cells), in comparison with the MN in unexposed women (9.50 MN/1000 cells). No statistically significant differences in MN frequency were observed by type of hair dye or color of the hair dye. Comparison of subjects in the highest quartile of MN frequency (> or = 12 MN/1000 cells) and those in the lowest quartile (< or = 4 MN/1000 cells) suggested an association between hair dye use and elevated MN frequency (OR 14.2 (95% CI 0.81-247.8; P=0.069)). None of the polymorphisms examined significantly modified association between hair dye use and frequency of MN. Findings of an increased frequency of MN in urothelial cells of hair dye users suggest a possible genotoxic effect of hair dye compounds and need confirmation in larger studies.

Air pollution and risk of urinary bladder cancer in a case-control study in Spain.

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.

Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study.

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.

Occupation and chronic bronchitis among Chinese women.

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.

Risk of bladder cancer associated with family history of cancer: do low-penetrance polymorphisms account for the increase in risk?

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 (P(trend) = 0.0004). A greater risk of bladder cancer was observed among those diagnosed at age

Bulky DNA adduct formation and risk of bladder cancer.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with risk of bladder cancer and with increased bulky DNA adduct levels in several studies, mainly in smokers. We investigated the relation between bulky PAH-DNA adducts in peripheral blood mononuclear cells and bladder cancer in nonsmoking subjects from a large hospital-based case-control study in Spain. Additionally, we examined the association between DNA adduct formation and several air pollution proxies. The study comprised 76 nonsmoking cases and 76 individually matched controls by sex, region of residence, age, and smoking status (never, former). To maximize the relevance of the DNA adduct measurement as a proxy of PAH exposure, subjects selected had not changed residence, occupation, and major lifestyle factors during the last 10 years. Bulky DNA adducts were measured using the (32)P-postlabeling technique, nuclease P1 treatment. The percentage of detectable adducts was higher in controls (41%) than in cases (32%) with an odds ratio of 0.75 (95% confidence interval, 0.36-1.58). In an analysis limited to controls, a higher percentage of DNA adducts was found among those whose last residence was in a big city (50%) compared with those living in villages (19%; P = 0.04). No consistent associations were found for other markers of air pollution. In this study, among nonsmokers with stable environmental and lifestyle factors, bulky DNA adducts were not associated with bladder cancer risk. Results do not support an association of bladder cancer risk with low-level exposure to PAHs as measured through the formation of bulky DNA adducts in peripheral mononuclear cells.

Food, nutrient and heterocyclic amine intake and the risk of bladder cancer.

Fruit and vegetable intake has been linked to bladder cancer risk; however, evidence for other foods or specific dietary factors is inconclusive. The association between diet and bladder cancer risk was evaluated among 912 incident bladder cancer cases and 873 controls in Spain. Data were consistent with a reduced bladder cancer risk associated with high fruit intake; however, the association was significant only among current smokers (OR (95% CI) for 5th versus 1st quintile: 0.5 (0.3-0.9), p trend=0.009). Evaluation of food subgroups showed significant inverse associations with high intakes of berries, Liliaceae vegetables and yellow-orange vegetables. The latter association was stronger among individuals with the GSTM1 present than the null genotype (0.4 (0.2, 0.7) and 0.9 (0.6, 1.3), respectively; p for interaction=0.04). Meat or fish intake, their cooking methods or level of doneness, or heterocyclic amine intakes were not significantly associated with risk. Intake of folate, other B-vitamins (B12, B6, B2) and retinol was also associated with a reduced risk, the strongest associations being for vitamin B6 (0.6 (0.4, 0.8) p trend=0.0006) and retinol (0.6 (0.4-0.9) p trend=0.004). Our findings indicate that fruit and vegetable intake, as well as B-vitamin and retinol intake might be associated with a reduced bladder cancer risk.