Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study

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 which > 97% 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 × days/year); and c) intensity-weighted cumulative exposure days (years of use × days/year × 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

An Updated Algorithm for Estimation of Pesticide Exposure Intensity in the Agricultural Health Study

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

Cancer Incidence among Pesticide Applicators Exposed to Cyanazine in the Agricultural Health Study

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 p(trend) 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

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 × 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

Race-Specific Cancer Mortality in US Firefighters: 1984-1993

A mortality odds ratio (MOR) study of race-specific cancer risk among firefighters was conducted using 1984-1993 death certificate data from 24 states. The Bureau of the Census Index of Industries and Occupations was used to code occupation on death certificates. The overall cancer mortality was slightly elevated among white firefighters (MOR = 1.1; 95% confidence interval [CI] = 1.1-1.2), but the increase in overall cancer mortality among black firefighters was not significant (MOR = 1.2; 95% CI = 0.9-1.5). Only prostate cancer risk was elevated in both groups (whitesMOR = 1.2; 95% CI = 1.0-1.3; blacksMOR = 1.9; 95% CI = 1.2-3.2). Among white firefighters, elevated site-specific cancer mortality risks were found for the following cancer siteslip (MOR = 5.9; 95% CI = 1.9-18.3), pancreas (MOR = 1.2; 95% CI = 1.0-1.5), soft tissue sarcoma (MOR = 1.6; 95% CI = 1.0-2.7), melanoma (MOR = 1.4; 95% CI = 1.0-1.9), kidney and renal pelvis (MOR = 1.3; 95% CI = 1.0-1.7), non-Hodgkin's lymphoma (MOR = 1.4; 95% CI = 1.1-1.7), and Hodgkin's disease (MOR = 2.4; 95% CI = 1.4-4.1). We also observed a slightly elevated risk for bronchus and lung cancer (MOR = 1.1; 95% CI = 1.0-1.2). Among black firefighters, excess risks were found for cancers of the brain and central nervous system (MOR = 6.9; 95% CI = 3.0-16.0), colon (MOR = 2.1; 95% CI = 1.1-4.0), and nasopharynx (MOR = 7.6; 95% CI = 1.3-46.4). Future studies are needed to confirm the existence of differential cancer mortality risks among firefighters of different race/ethnic subpopulations

Cancer Incidence Among Pesticide Applicators Exposed to Atrazine in the Agricultural Health Study

Background: 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. Methods: 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. Ptrend 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. Results: 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 (RRLD) and intensity-weighted lifetime days (RRIWLD) of exposure yielded the following results: prostate cancer, RRLD = 0.88, 95% CI = 0.63 to 1.23, Ptrend = .26, and RRIWLD = 0.89, 95% CI = 0.63 to 1.25, Ptrend = .35; lung cancer, RRLD = 1.91, 95% CI = 0.93 to 3.94, Ptrend = .08, and RRIWLD = 1.37, 95% CI = 0.65 to 2.86, Ptrend = .19; bladder cancer, RRLD = 3.06, 95% CI = 0.86 to 10.81, Ptrend =.18, and RRIWLD = 0.85, 95% CI = 0.24 to 2.94, Ptrend = .71; non-Hodgkin lymphoma, RRLD = 1.61, 95% CI = 0.62 to 4.16, Ptrend = .35, and RRIWLD = 1.75, 95% CI = 0.73 to 4.20, Ptrend = .14; and multiple myeloma, RRLD = 1.60, 95% CI = 0.37 to 7.01, Ptrend = .41, and RRIWLD = 2.17, 95% CI = 0.45 to 10.32, Ptrend = .21. Conclusions: 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)