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To address concerns among Gulf Coast residents about ongoing exposures to volatile organic compounds, including benzene, toluene, ethylbenzene, o-xylene, and m-xylene/p-xylene (BTEX), we characterized current blood levels and identified predictors of BTEX among Gulf state residents. We collected questionnaire data on recent exposures and measured blood BTEX levels in a convenience sample of 718 Gulf residents. Because BTEX is rapidly cleared from the body, blood levels represent recent exposures in the past 24 h. We compared participants' levels of blood BTEX to a nationally representative sample. Among nonsmokers we assessed predictors of blood BTEX levels using linear regression, and predicted the risk of elevated BTEX levels using modified Poisson regression. Blood BTEX levels in Gulf residents were similar to national levels. Among nonsmokers, sex and reporting recent smoky/chemical odors predicted blood BTEX. The change in log benzene was -0.26 (95% CI: -0.47, -0.04) and 0.72 (0.02, 1.42) for women and those who reported odors, respectively. Season, time spent away from home, and self-reported residential proximity to Superfund sites (within a half mile) were statistically associated with benzene only, however mean concentration was nearly an order of magnitude below that of cigarette smokers. Among these Gulf residents, smoking was the primary contributor to blood BTEX levels, but other factors were also relevant.

Background: Adverse mental health effects have been reported following oil spills but few studies have identified specific responsible attributes of the clean-up experience. We aimed to analyse the effects of the 2010 Deepwater Horizon (Gulf of Mexico) disaster on the mental health of individuals involved in oil spill response and clean-up., Methods: We used data from the Gulf Long-term Follow-up Study, a cohort of workers and volunteers involved in oil spill clean-up after the Deepwater Horizon disaster. We included 8968 workers (hired after completing training for oil spill response and clean-up) and 2225 non-workers (completed training but were not hired) who completed a Patient Health Questionnaire-8 and four-item Primary Care PTSD Screen to assess for probable depression and post-traumatic stress disorder (PTSD) indicators. Participants were recruited between March 28, 2011, and March 29, 2013. The mental health indicators were assessed at home visits done between May 12, 2011, and May 15, 2013. We used regression models to analyse the effect of potentially stressful job experiences, job type, and total hydrocarbon exposure on mental health indicators., Findings: Oil spill response and clean-up work was associated with increased prevalence of depression (prevalence ratio [PR] 1·22, 95% CI 1·08-1·37) and PTSD (PR 1·35, 95% CI 1·07-1·71). Among workers, individuals who reported smelling oil, dispersants, or cleaning chemicals had an elevated prevalence of depression (1·56, 1·37-1·78) and PTSD (2·25, 1·71-2·96). Stopping work because of the heat was also associated with depression (1·37, 1·23-1·53) and PTSD (1·41, 1·15-1·74), as was working as a commercial fisherman before the spill (1·38, 1·21-1·57; and 2·01, 1·58-2·55, respectively). An increase in exposure to total hydrocarbons appeared to be associated with depression and PTSD, but after taking into account oil spill job experiences, only the association between the highest amount of total hydrocarbons and PTSD remained (1·75, 1·11-2·76)., Interpretation: Oil spill clean-up workers with high amounts of total hydrocarbon exposure or potentially stressful job experiences had an increased prevalence of depression and PTSD. These findings provide evidence that response and clean-up work is associated with adverse psychological effects and suggest the need for mental health services both before and after the event., Funding: National Institutes of Health (NIH) Common Fund and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival., Methods: We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively., Results: EA incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 = 1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95% CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ≤ 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4-5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.05, 95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA-glycaemic index association was elevated for BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.38, 95% CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but for GERD ≥ weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival., Conclusions: If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies., (Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

Background: Grilled, barbecued, and smoked meat intake, a prevalent dietary source of polycyclic aromatic hydrocarbon (PAH) carcinogens, may increase the risk of incident breast cancer. However, no studies have examined whether intake of this PAH source influences survival after breast cancer., Methods: We interviewed a population-based cohort of 1508 women diagnosed with first primary invasive or in situ breast cancer in 1996 and 1997 at baseline and again approximately five years later to assess grilled/barbecued and smoked meat intake. After a median of 17.6 years of follow-up, 597 deaths, of which 237 were breast cancer related, were identified. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality as related to prediagnosis intake, comparing high (above the median) to low intake, as well as postdiagnosis changes in intake, comparing every combination of pre-/postdiagnosis intake to low pre-/postdiagnosis intake. All statistical tests were two-sided., Results: High prediagnosis grilled/barbecued and smoked meat intake was associated with increased risk of all-cause mortality (HR = 1.23, 95% CI = 1.03 to 1.46). Other associations were noted, but estimates were not statistically significant. These include high prediagnosis smoked beef/lamb/pork intake and increased all-cause (HR = 1.17, 95% CI = 0.99 to 1.38, P trend = .10) and breast cancer-specific (HR = 1.23, 95% CI = 0.95 to 1.60, P trend = .09) mortality. Also, among women with continued high grilled/barbecued and smoked meat intake after diagnosis, all-cause mortality risk was elevated 31% (HR = 1.31, 95% CI = 0.96 to 1.78). Further, breast cancer-specific mortality was decreased among women with any pre- and postdiagnosis intake of smoked poultry/fish (HR = 0.55, 95% CI = 0.31 to 0.97)., Conclusion: High intake of grilled/barbecued and smoked meat may increase mortality after breast cancer., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals., (© 2015 UICC.)

Background: Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer., Methods: In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Results: When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86)., Discussion: PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence., (Published by Elsevier Inc.)

Background: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure., Objectives: Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence., Methods: Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996-1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960-1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH-DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression., Results: The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960-1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic-breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]., Conclusions: In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise., Citation: Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30-38; http://dx.doi.org/10.1289/ehp.1307736.

Objectives: Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 39 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina., Methods: Via linkage to the US Renal Data System, we identified 320 ESRD cases diagnosed between enrolment (1993-1997) and December 2011 among 55 580 male licensed pesticide applicators. Participants provided information on use of pesticides via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: (1) ordinal categories of intensity-weighted lifetime use of 39 pesticides, (2) poisoning and high-level pesticide exposures and (3) pesticide exposure resulting in a medical visit or hospitalisation., Results: Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide permethrin. More than one medical visit due to pesticide use (HR=2.13; 95% CI 1.17 to 3.89) and hospitalisation due to pesticide use (HR=3.05; 95% CI 1.67 to 5.58) were significantly associated with ESRD., Conclusions: Our findings support an association between ESRD and chronic exposure to specific pesticides, and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD., Clinical Trial Registration: Clinicaltrials.gov NCT00352924., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Classical statistical methods for analyzing exposure data with values below the detection limits are well described in the occupational hygiene literature, but an evaluation of a Bayesian approach for handling such data is currently lacking. Here, we first describe a Bayesian framework for analyzing censored data. We then present the results of a simulation study conducted to compare the β-substitution method with a Bayesian method for exposure datasets drawn from lognormal distributions and mixed lognormal distributions with varying sample sizes, geometric standard deviations (GSDs), and censoring for single and multiple limits of detection. For each set of factors, estimates for the arithmetic mean (AM), geometric mean, GSD, and the 95th percentile (X0.95) of the exposure distribution were obtained. We evaluated the performance of each method using relative bias, the root mean squared error (rMSE), and coverage (the proportion of the computed 95% uncertainty intervals containing the true value). The Bayesian method using non-informative priors and the β-substitution method were generally comparable in bias and rMSE when estimating the AM and GM. For the GSD and the 95th percentile, the Bayesian method with non-informative priors was more biased and had a higher rMSE than the β-substitution method, but use of more informative priors generally improved the Bayesian method's performance, making both the bias and the rMSE more comparable to the β-substitution method. An advantage of the Bayesian method is that it provided estimates of uncertainty for these parameters of interest and good coverage, whereas the β-substitution method only provided estimates of uncertainty for the AM, and coverage was not as consistent. Selection of one or the other method depends on the needs of the practitioner, the availability of prior information, and the distribution characteristics of the measurement data. We suggest the use of Bayesian methods if the practitioner has the computational resources and prior information, as the method would generally provide accurate estimates and also provides the distributions of all of the parameters, which could be useful for making decisions in some applications., (© The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N=31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities., Methods: AHS participants reported pesticide exposure via self-administered questionnaires at enrollment (1993-1997). ESRD cases were identified via linkage to the United States Renal Data System. Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment. Models of associations with farming and household factors were additionally adjusted for personal use of pesticides., Results: We identified 98 ESRD cases diagnosed between enrollment and 31 December 2011. Although women who ever applied pesticides (56% of cohort) were less likely than those who did not apply to develop ESRD (Hazard Ratio (HR): 0.42; 95% CI: 0.28, 0.64), among women who did apply pesticides, the rate of ESRD was significantly elevated among those who reported the highest (vs. lowest) cumulative general pesticide use (HR: 4.22; 95% CI: 1.26, 14.20). Among wives who never applied pesticides, ESRD was associated with husbands' ever use of paraquat (HR=1.99; 95% CI: 1.14, 3.47) and butylate (HR=1.71; 95% CI: 1.00, 2.95), with a positive exposure-response pattern for husband's cumulative use of these pesticides., Conclusions: ESRD may be associated with direct and/or indirect exposure to pesticides among farm women. Future studies should evaluate indirect exposure risk among other rural populations., (Published by Elsevier Inc.)

Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient ≥0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population., (Published by Elsevier Ltd.)

Purpose: Flavonoids, concentrated in fruits and vegetables, demonstrate in experimental studies chemopreventive properties in relation to Barrett's esophagus (BE), a precursor lesion for esophageal adenocarcinoma. One case-control investigation reported an inverse association between isoflavone intake and odds of BE, yet no epidemiologic study has considered other flavonoid classes, which are more commonly consumed by Americans., Methods: We examined intake of total flavonoids, six flavonoid classes, and lignans among case-control study participants in western Washington State. Food frequency questionnaires were self-completed by BE cases with specialized intestinal metaplasia (n = 170) and matched controls (n = 183)., Results: In logistic regression models adjusted for age, sex, body mass index, and energy intake, the odds ratio (OR) for specialized intestinal metaplasia BE associated with anthocyanidin intake was 0.49 (95% confidence interval: 0.30-0.80, for quartiles 2-4 combined vs. quartile 1), for which wine and fruit juice were major dietary sources. More moderate decreased ORs were noted for flavanones, flavonols, isoflavones, and lignans. A modest increased OR was observed for flavones, for which pizza was the main dietary source in our population., Conclusions: Our findings of an inverse association between anthocyanidins and odds of BE suggest that adequate dietary intake of these compounds may lower risk of this cancer precursor lesion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Organochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern., Objectives: We conducted a nested case-control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway., Methods: Sera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression., Results: Metastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log-transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02)., Conclusions: Our study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer., Citation: Koutros S, Langseth H, Grimsrud TK, Barr DB, Vermeulen R, Portengen L, Wacholder S, Beane Freeman LE, Blair A, Hayes RB, Rothman N, Engel LS. 2015. Prediagnostic serum organochlorine concentrations and metastatic prostate cancer: a nested case-control study in the Norwegian Janus Serum Bank cohort. Environ Health Perspect 123:867-872; http://dx.doi.org/10.1289/ehp.1408245.

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans., Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed., Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed., Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

High rates of mental health (MH) problems have been documented among disaster relief workers. However, few workers utilize MH services, and predictors of service use among this group remain unexplored. The purpose of this study was to explore associations between predisposing, illness-related, and enabling factors from Andersen's behavioral model of treatment-seeking and patterns of service use among participants who completed at least one full day of cleanup work after the Deepwater Horizon oil spill and participated in home visits for the NIEHS GuLF STUDY (N = 8931). Workers reported on MH symptoms and whether they had used counseling or medication for MH problems since the oil spill. Hierarchical logistic regression models explored associations between predictors and counseling and medication use in the full sample, and type of use (counseling only, medication only, both) among participants who used either service. Analyses were replicated for subsamples of participants with and without symptom inventory scores suggestive of probable post-disaster mental illness. Having a pre-spill MH diagnosis, pre-spill service use, more severe post-spill MH symptoms, and healthcare coverage were positively associated with counseling and medication use in the full sample. Among participants who used either service, non-Hispanic Black race, pre-spill counseling, lower depression, and not identifying a personal doctor or healthcare provider were predictive of counseling only, whereas older age, female gender and pre-spill medication were predictive of medication only. The results were generally consistent among participants with and without probable post-disaster mental illness. The results suggest variability in which factors within Andersen's behavioral model are predictive of different patterns of service use among disaster relief workers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Agricultural pesticide handlers are at an elevated risk for overexposure to organophosphate (OP) pesticides, but symptoms can be difficult to recognise, making biomarkers invaluable for diagnosis. Occupational monitoring programmes for cholinesterase depression generally rely on measuring activity of either of the two common blood cholinesterases which serve as proxy measurements for nervous-system acetylcholinesterase activity: red blood cell acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE). These biomarkers, however, may be affected differentially by some OPs and the relationship between them has not been well characterised. We aim to determine the association between blood AChE and BChE activity levels and assess whether they produce comparable classifications of clinical cholinesterase depression among OP pesticide handlers., Methods: Using blood samples from 215 participants of the Washington State Cholinesterase Monitoring Program, we quantified changes in AChE and BChE activity from before and after exposure to OP pesticides and calculated Pearson correlation statistics for correlation of AChE and BChE changes in activity, as well as weighted κ statistics for agreement of classification of clinical cholinesterase depression based on AChE versus BChE measurements., Results: AChE and BChE activity measurements are weakly negatively correlated in our study population. Reaching a clinical threshold for diagnosis of cholinesterase depression based on the AChE marker did not correlate with reaching clinical depression based on the BChE marker., Conclusions: Both AChE and BChE should be measured in monitoring programmes because they may both give potentially important but disparate classifications of clinical cholinesterase depression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The National Institute for Environmental Health Sciences (NIEHS) is conducting an epidemiologic study (GuLF STUDY) to investigate the health of the workers and volunteers who participated from April to December of 2010 in the response and cleanup of the oil release after the Deepwater Horizon explosion in the Gulf of Mexico. The exposure assessment component of the study involves analyzing thousands of personal monitoring measurements that were collected during this effort. A substantial portion of these data has values reported by the analytic laboratories to be below the limits of detection (LOD). A simulation study was conducted to evaluate three established methods for analyzing data with censored observations to estimate the arithmetic mean (AM), geometric mean (GM), geometric standard deviation (GSD), and the 95th percentile (X0.95) of the exposure distribution: the maximum likelihood (ML) estimation, the β-substitution, and the Kaplan-Meier (K-M) methods. Each method was challenged with computer-generated exposure datasets drawn from lognormal and mixed lognormal distributions with sample sizes (N) varying from 5 to 100, GSDs ranging from 2 to 5, and censoring levels ranging from 10 to 90%, with single and multiple LODs. Using relative bias and relative root mean squared error (rMSE) as the evaluation metrics, the β-substitution method generally performed as well or better than the ML and K-M methods in most simulated lognormal and mixed lognormal distribution conditions. The ML method was suitable for large sample sizes (N ≥ 30) up to 80% censoring for lognormal distributions with small variability (GSD = 2-3). The K-M method generally provided accurate estimates of the AM when the censoring was <50% for lognormal and mixed distributions. The accuracy and precision of all methods decreased under high variability (GSD = 4 and 5) and small to moderate sample sizes (N < 20) but the β-substitution was still the best of the three methods. When using the ML method, practitioners are cautioned to be aware of different ways of estimating the AM as they could lead to biased interpretation. A limitation of the β-substitution method is the absence of a confidence interval for the estimate. More research is needed to develop methods that could improve the estimation accuracy for small sample sizes and high percent censored data and also provide uncertainty intervals., (© The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Purpose: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population., Methods: A nested case-control study was conducted among members of the Health Alliance Plan HMO of the Henry Ford Health System enrolled between 1999 and 2010. Electronic pharmacy records of statin use were compared among tumor registry-confirmed cases of HCC (n=94) and controls (n=468) matched on age, sex, diagnosis date, and length of HMO enrolment., Results: In multivariate analyses, ever-use of statins was significantly inversely associated with development of HCC (Odds ratio (OR): 0.32, 95%CI: 0.15-0.67). No clear dose-response relationship was evident as statin use for <2 years (OR=0.32, 95%CI=0.13-0.83) and >2 years (OR=0.31, 95CI%=0.12-9.81) resulted in very similar ORs., Conclusions: The use of statins among populations in low-risk HCC areas may be associated with decreased risk of HCC., (Published by Elsevier Ltd.)

This paper develops a hierarchical framework for identifying spatiotemporal patterns in data with a high degree of censoring using the gradient process. To do this, we impute censored values using a sampling-based inverse CDF method within our Markov chain Monte Carlo algorithm, thereby avoiding burdensome integration and facilitating efficient estimation of other model parameters. We illustrate use of our methodology using a simulated data example, and uncover the danger of simply substituting a space- and time-constant function of the level of detection for all missing values. We then fit our model to area measurement data of volatile organic compounds (VOC) air concentrations collected on vessels supporting the response and clean-up efforts of the Deepwater Horizon oil release that occurred starting April 20, 2010. These data contained a high percentage of observations below the detectable limits of the measuring instrument. Despite this, we were still able to make some interesting discoveries, including elevated levels of VOC near the site of the oil well on June 26th. Using the results from this preliminary analysis, we hope to inform future research on the Deepwater Horizon study, including the use of gradient methods for assigning workers to exposure categories.

Background: Exposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations., Objectives: We sought to identify predictors of exposure and to assess the reproducibility of phenol concentrations across serial spot urine samples among Chinese adults., Methods: We measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997-2006 from 50 participants of the Shanghai Women's Health Study cohort and during 2002-2006 from 50 participants of the Shanghai Men's Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test, and assessed reproducibility among serial samples using intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs)., Results: Creatinine-corrected phenol concentrations were generally higher among women than men. Participants who had taken medicine within the previous 24 hr had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC = 0.54-0.60, SCC = 0.43-0.56), but lower for other analytes (ICC = 0.20-0.29). Reproducibility among women was low (ICC = 0.13-0.39), but increased when restricted to morning-only urine samples., Conclusions: Among these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women.

Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (1993-2001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n = 22), near-hits (n = 19), otherwise well-established risk loci (n = 5), or located in the same genes as selected variants (n = 37). We successfully replicated 18 GWAS-identified SNPs in whites (n = 2,352) and 10 in African Americans (n = 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancer-related SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations.

Background: Epidemiologic evidence suggests a negative relation between sunlight exposure and breast cancer risk. The hypothesized mechanism is sunlight-induced cutaneous synthesis of vitamin D., Objectives: Our goal was to examine sun exposure and its interaction with vitamin D receptor (VDR) gene variants on breast cancer risk., Methods: We examined sun exposure and breast cancer incidence among 31,021 private pesticide applicators' wives, including 578 cases, enrolled in the prospective Agricultural Health Study cohort and followed 8.6 years on average. We estimated interactions between sun exposure, VDR variants, and breast cancer in a nested case-control study comprising 293 cases and 586 matched controls. Information on sun exposure was obtained by questionnaire at cohort enrollment. Relative risks were estimated using Cox proportional hazards regression for the cohort data and conditional logistic regression for the nested case-control data., Results: We observed a small decrease in breast cancer risk in association with usual sun exposure of ≥ 1 hr/day (versus < 1 hr/day) 10 years before the start of follow-up among all participants [hazard ratio (HR) = 0.8; 95% CI: 0.6, 1.0]. The association appeared to be slightly stronger in relation to estrogen receptor-positive tumors (HR = 0.7; 95% CI: 0.5, 0.9) than estrogen receptor-negative tumors (HR = 1.1; 95% CI: 0.6, 2.1). The HR for joint exposure ≥ 1 hr/day of sunlight and one VDR haplotype was less than expected given negative HRs for each individual exposure (interaction p-value = 0.07)., Conclusion: Our results suggest that sun exposure may be associated with reduced risk of breast cancer, but we did not find clear evidence of modification by VDR variants. Larger studies are warranted, particularly among populations in whom low levels of usual sun exposure can be more precisely characterized.

Background: Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least five immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study., Methods: We used Bayesian polytomous logistic regression to estimate ORs and 95% posterior intervals for the association between each of 78 single nucleotide polymorphisms (SNP) and five breast cancer subtypes. Subtypes were defined using five immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2), and cytokeratin (CK) 5/6., Results: Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), or HER2+/ER- disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1., Conclusion and Impact: We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes. .

Background: Gastrointestinal stromal tumors are rare soft tissue sarcomas that typically develop from mesenchymal cells with acquired gain-in-function mutations in KIT or PDGFRA oncogenes. These somatic mutations have been well-characterized, but little is known about inherited genetic risk factors. Given evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations in other cancers, we hypothesized that these signature KIT or PDGFRA mutations may be similarly fundamental to understanding gastrointestinal stromal tumor etiology. Therefore, we examined associations between 522 single nucleotide polymorphisms and seven KIT or PDGFRA tumor mutations types. Candidate pathways included dioxin response, toxin metabolism, matrix metalloproteinase production, and immune and inflammatory response., Methods: We estimated odds ratios and 95% confidence intervals for associations between each candidate SNP and tumor mutation type in 279 individuals from a clinical trial of adjuvant imatinib mesylate. We used sequence kernel association tests to look for pathway-level associations., Results: One variant, rs1716 on ITGAE, was significantly associated with KIT exon 11 non-codon 557-8 deletions (odds ratio = 2.86, 95% confidence interval: 1.71-4.78) after adjustment for multiple comparisons. Other noteworthy associations included rs3024498 (IL10) and rs1050783 (F13A1) with PDGFRA mutations, rs2071888 (TAPBP) with wild type tumors and several matrix metalloproteinase SNPs with KIT exon 11 codon 557-558 deletions. Several pathways were strongly associated with somatic mutations in PDGFRA, including defense response (p = 0.005) and negative regulation of immune response (p = 0.01)., Conclusions: This exploratory analysis offers novel insights into gastrointestinal stromal tumor etiology and provides a starting point for future studies of genetic and environmental risk factors for the disease.

Gastrointestinal stromal tumors (GISTs) are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs) in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT). Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836) and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836). CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively). Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic origins and provides a starting point for future candidate gene or gene-environment research.

Background: Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitamin D are mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent., Methods: We investigated VDR polymorphisms and haplotypes in relation to breast cancer risk by genotyping 26 single nucleotide polymorphisms (SNP) that (i) had known/suspected impact on VDR function, (ii) were tagging SNPs for the three VDR haplotype blocks among whites, or (iii) were previously associated with breast cancer risk. We estimated odds ratios (OR) and 95% confidence intervals (CI) in relation to breast cancer risk among 270 incident cases and 554 matched controls within the Agricultural Health Study cohort., Results: In individual SNP analyses, homozygous carriers of the minor allele for rs2544038 had significantly increased breast cancer risk (OR = 1.5; 95% CI: 1.0-2.5) and homozygous carriers of the minor allele for rs11168287 had significantly decreased risk (OR = 0.6; 95% CI: 0.4-1.0). Carriers of the minor allele for rs2239181 exhibited marginally significant association with risk (OR = 1.4; 95% CI: 0.9-2.0). Haplotype analyses revealed three haplotype groups (blocks "A," "B," and "C"). Haplotype GTCATTTCCTA in block B was significantly associated with reduced risk (OR = 0.5; 95% CI: 0.3-0.9)., Conclusions: These results suggest that variation in VDR may be associated with breast cancer risk., Impact: Our findings may help guide future research needed to define the role of vitamin D in breast cancer prevention., (2012 AACR)

Background: Xuanwei, China, experiences some of the highest rates of lung cancer in China. While lung cancer risk has been linked to the household use of bituminous coal, no study has comprehensively evaluated the risk of lung cancer associated with the mining of this coal in Xuanwei. In Xuanwei, coal is typically extracted from underground mines, without ventilation, and transported to the surface using carts powered by manpower or electricity., Methods: We evaluated the risk of lung cancer and working as a coal miner, in the absence of diesel exhaust exposure, in a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls with information on occupational histories. Odds ratios (ORs) and 95% confidence intervals (CIs) for working as a coal miner and years of working as a coal miner were calculated by conditional logistic regression, adjusting for potential confounders, such as smoking and household coal use., Results: We observed an increased risk of lung cancer among coal miners (OR = 2.7; 95%CI = 1.3-5.6) compared to noncoal miners. Further, a dose-response relationship was observed for the risk of lung cancer and the number of years working as a coal miner (P(trend)  = 0.02), with those working as miners for more than 10 years experiencing an almost fourfold increased risk (OR = 3.8; 95%CI = 1.4-10.3) compared to noncoal miners., Conclusions: These findings suggest that coal mining in Xuanwei may be a risk factor for lung cancer., (Copyright © 2011 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Recent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs)., Objective: To further investigate this question, we conducted a nested case-control study of TGCTs within the Norwegian Janus Serum Bank cohort., Methods: The study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27-62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case-control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression., Results: TGCT cases had elevated concentrations of p,p'-DDE (tertile 3 vs. tertile 1 OR (OR(T3)) 2.2; 95% CI, 0.7-6.5; p(Wilcoxon) = 0.07), oxychlordane (OR(T3) 3.2; 95% CI, 0.6-16.8; p(Wilcoxon) = 0.05), trans-nonachlor (OR(T3) 2.6; 95% CI, 0.7-8.9; p(Wilcoxon) = 0.07), and total chlordanes (OR(T3) 2.0; 95% CI, 0.6-7.2; p(Wilcoxon) = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195., Conclusions: Our study provides additional but qualified evidence supporting an association between exposures to p,p'-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk.

Background & Aims: The incidence of esophageal and gastric cardia adenocarcinoma has increased in Western countries in recent decades for largely unknown reasons. We investigated whether use of LES-relaxing drugs was related to an increased risk of esophageal and gastric cardia adenocarcinoma, and whether use of NSAIDs was related to a reduced risk of esophageal and gastric cancers., Methods: We examined these associations by using administrative databases in a case-control study in 2 integrated health care delivery systems. Cases were incident esophageal adenocarcinomas (n = 163) and squamous cell carcinomas (n = 114) and gastric cardia (n = 176) and non-cardia adenocarcinomas (n = 320), diagnosed between 1980-2002 in one health system and between 1993-2002 in the other. Matched controls (n = 3996) were selected. Complete prescription information was available for the study period., Results: Prescription of corticosteroids was associated with a decreased risk of esophageal adenocarcinoma (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4-0.9), esophageal squamous cell carcinoma (OR, 0.4; 95% CI, 0.2-0.6), and gastric non-cardia carcinoma (OR, 0.4, 95% CI, 0.3-0.6). Ever use of pharmacy-purchased aspirin was associated with 30%-60% decreased risks of the studied cancers. As a group, LES-relaxing drugs showed little evidence of association with increased risk of any esophageal or gastric cancer., Conclusions: Corticosteroid and aspirin use were associated with significantly decreased risks of esophageal and gastric cancer. LES-relaxing drugs as a group did not affect these risks, although we had limited power to assess individual drugs. The possibility that corticosteroids and aspirin might reduce esophageal cancer risk warrants further consideration.

The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.

Several epidemiologic studies suggest that polychlorinated biphenyl (PCB) levels measured in peripheral blood or adipose tissue are related to increased risk of non-Hodgkin lymphoma (NHL) and, therefore, may be at least partially responsible for the rising incidence of NHL unrelated to HIV infection in recent decades. Case-control studies that measured PCBs in blood, adipose tissue, or household carpet dust, at the time of diagnosis, have observed elevated NHL risk associated with concentrations of either total PCBs or of specific congeners. Similar associations have been found in a number of prospective cohorts. These associations do not seem to be due to confounding by other organochlorines or by other known NHL risk factors. These results support evidence of PCB carcinogenicity from animal studies. However, interpretation of the epidemiologic evidence is limited by the wide range in measurement precision across congeners and by the moderate to high correlation among many congeners. Occupational cohort studies provide very limited support for a relationship between PCBs and NHL. In conclusion, there is mounting evidence of a relationship between certain PCBs and risk of NHL, but important questions remain, especially regarding the magnitude, timing, and causality of that relationship.

Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate levels of pesticides. We analyzed cross-sectional data from 18,782 white male licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993-1997. Applicators provided information on lifetime pesticide use and 23 neurologic symptoms typically associated with pesticide intoxication. An indicator of more symptoms (> or = 10 vs. < 10) during the year before enrollment was associated with cumulative lifetime days of insecticide use: odds ratios (95% confidence intervals) were 1.64 (1.36-1.97) for 1-50 days, 1.89 (1.58-2.25) for 51-500 days, and 2.50 (2.00-3.13) for > 500 days, compared with never users. A modest association for fumigants [> 50 days, 1.50 (1.24-1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99-1.75)] and fungicides [> 50 days, 1.23 (1.00-1.50)] were observed. Pesticide use within the year before enrollment was not associated with symptom count. Only associations with insecticides and fumigants persisted when all four pesticide groups were examined simultaneously. Among chemical classes of insecticides, associations were strongest for organophosphates and organochlorines. Associations with cumulative exposure persisted after excluding individuals who had a history of pesticide poisoning or had experienced an event involving high personal pesticide exposure. These results suggest that self-reported neurologic symptoms are associated with cumulative exposure to moderate levels of fumigants and organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.

Objectives and Methods: Risks of oral cancer related to a CA microsatellite repeat polymorphism in intron 1 of the epidermal growth factor receptor (EGFR) gene and a TaqI polymorphism in the transforming growth factor-alpha (TGFA) gene were evaluated in a population-based case-control study consisting of 157 cases and 149 controls recruited in Puerto Rico., Results: Carriers of > or = 16 CA repeats in EGFR showed a 1.9-fold increased risk for oral cancer (OR=1.9, 95% CI=1.0-3.5). Risks also tended to increase with decreasing number of alleles with > or = 16 CA repeats (P for trend=0.06). Our data suggested a non-significant reduction in risk for subjects heterozygous for the TGFA polymorphism (OR=0.6, 95% CI=0.2-1.3)., Conclusions: The EGFR-associated risk appeared to be independent of tobacco and alcohol use and may be restricted primarily to subjects who consumed low amounts of fresh fruits and vegetables (OR=5.9, 95%CI: 2.3-15.2). These data implicate dietary and molecular targets for oral cancer prevention.

The authors examined the association between pesticide use and breast cancer incidence among farmers' wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993-1997. Information on pesticide use and other information was obtained by self-administered questionnaire at enrollment from the women and their husbands. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk.

For individuals with multiple exposures to bone marrow mutagens the glycophorin A (GPA) assay appears to detect the cumulative genotoxic effects of these nonspecific exposures. To determine whether workers exposed to organophosphates and/or carbamate pesticides have more GPA variants compared with controls, this cross-sectional cohort study examined 67 Latino farm workers, most of whom were exposed to organophosphate or carbamate pesticides, and 68 age-, gender-, ethnicity-, and education-matched reference subjects. Of the 27 participants who completed the questionnaire and had the M/N alleleotype required for the GPA assay, the N/N variant frequency was 9.1 x 10(-6) in the ten subjects with more than 1,500 cumulative hours of exposure vs 3.8 x 10(-6) in the six referent subjects with no known pesticide exposure (p = 0.097). A consistent trend with increasing cumulative exposure was found for N/N and O/N allele-loss frequencies when exposures were stratified into three groups. Despite the small sample size due to the alleleotype restriction, these findings support the hypothesis that some pesticides are mutagenic to hematopoietic stem cells.

An icon-calendar interview form (ICF) for a case-control study of childhood leukemias and parental exposures to pesticides is described. It includes calendar sheets, icons for life events, crops, jobs, regions, non-agricultural jobs, application techniques and personal protection, markers for durations of exposure patterns, and checklists of pesticides. The ICF collects monthly data from two years before birth until diagnosis of cancer (index children) or until either the interview date or age 15 (controls). Data ascertainment was easy in 62% of interviews, moderately easy in 32%, and difficult in 6%. Seventy-eight subjects delivered data on specific pesticides with pesticide checklists, which improved identification of pesticides. ICF performs satisfactorily for crops, tasks, and other determinants of exposure. Data on pesticides will be further improved by introducing external data use on different crops, time periods, and regions, and by exposure modeling for 27 pesticides.

Background: Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population-based case-control study., Methods: We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation., Results: Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%)., Conclusion: In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables.

Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians results in a lack of GSTM1 enzyme activity. Most studies examining the relation between bladder cancer and GSTM1 have reported an increased risk associated with a lack of GSTM1 activity. The authors performed meta- and pooled analyses of published and unpublished, case-control, genotype-based studies that examined this association (17 studies, 2,149 cases, 3,646 controls) and excluded studies conducted in populations with a high prevalence of exposure to known bladder cancer risk factors other than tobacco smoke. Using random effects models in the meta-analysis, the authors obtained a summary odds ratio of 1.44 (95% confidence interval (CI): 1.23, 1.68) for GSTM1 null status with all studies included. Results from studies with at least 100 cases and 100 controls produced a summary odds ratio of 1.42 (95% CI: 1.26, 1.60). Pooled analyses using original data sets from 10 studies (1,496 cases and 1,444 controls) and adjusting for age, sex, and race produced similar results. There was no evidence of multiplicative interaction between the GSTM1 null genotype and ever smoking in relation to bladder cancer, although there was a suggestion of additive interaction (additive interaction = 0.45, 95% CI: -0.03, 0.93). These results indicate that, among populations studied to date, GSTM1 null status is associated with a modest increase in the risk of bladder cancer.

Background: Adenocarcinomas of the esophagus and gastric cardia have risen dramatically in incidence over the past few decades, however, little research has been conducted on the occupational risk factors for these cancers., Methods: In this population-based case-control study, lifetime job histories were compared between cases of esophageal adenocarcinoma (n = 283), gastric cardia adenocarcinoma (n = 259), and population controls (n = 689). Odds ratios (OR) and 95% confidence intervals (CI) for ever employment and by duration in various occupational and industrial categories were calculated using unconditional logistic regression., Results: The risk of esophageal adenocarcinoma was elevated for persons ever employed in administrative support (OR = 1.5; 95%CI = 1.0-2.1); financial, insurance, and real estate (OR = 1.6; 95%CI = 1.0-2.4); and health services (OR = 2.2; 95%CI = 1.2-3.9). The risk of gastric cardia adenocarcinoma was increased among transportation workers (OR = 1.7; 95%CI = 1.1-2.6), as well as among carpenters (OR = 1.8; 95%CI = 0.9-3.9) and workers in the furniture manufacturing industry (OR = 2.4; 95%CI = 0.9-6.3). However, we observed few duration-response relations between length of employment in any category and cancer risk., Conclusions: This study revealed associations of esophageal adenocarcinoma with employment in administrative support, health services, and a category of financial, insurance, and real estate industries, and of gastric cardia adenocarcinoma with transportation and certain woodworking occupations. Some of these findings may be due to the play of chance associated with the multiple comparisons made in this study. Our results suggest that, overall, workplace exposures play a minor role in the etiology and upward trend of esophageal and gastric cardia adenocarcinomas.

Epidemiological studies are increasingly collecting buccal cells and other sources of DNA for genetic analysis. However, high refusal rates raise concerns about possible selection bias. This study examines the subject characteristics associated with refusal or failure to provide a buccal cell sample. Subjects were male farmers in the Agricultural Health Study, which is being conducted in Iowa and North Carolina. As part of a 5-year follow-up, cohort members were contacted by telephone and asked to participate in a telephone interview and to consent to providing a buccal cell sample using a kit that was mailed to them. Demographic, lifestyle, disease, and occupational characteristics were compared between consenters who returned a sample ("compliers"), nonconsenters ("refusers"), and consenters who failed to return a sample ("noncompliers"). Compliers (n = 8794), refusers (n = 3178), and noncompliers (n = 3008) were quite similar, although compliers tended to be slightly older. Although some significant differences between these groups were observed, the magnitude of these differences was generally small, usually no more than a few percentage points. In conclusion, this study found little difference between male farmers who agreed to provide buccal cell samples versus those who either refused to provide a sample or who agreed but failed to return the sample. Observed differences were typically small and would be unlikely to compromise etiologic associations identified in such a prospective study. In short, there appears to be little selection bias in the Agricultural Health Study buccal cell collection process, further supporting the use of such mailed collection kits in epidemiological research.