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Steroid 5β-reductase (AKR1D1) plays important role in hepatic bile acid synthesis and glucocorticoid clearance. Bile acids and glucocorticoids are potent metabolic regulators, but whether AKR1D1 controls metabolic phenotype in vivo is unknown. Akr1d1–/– mice were generated on a C57BL/6 background. Liquid chromatography/mass spectrometry, metabolomic and transcriptomic approaches were used to determine effects on glucocorticoid and bile acid homeostasis. Metabolic phenotypes including body weight and composition, lipid homeostasis, glucose tolerance and insulin tolerance were evaluated. Molecular changes were assessed by RNA-Seq and Western blotting. Male Akr1d1–/– mice were challenged with a high fat diet (60% kcal from fat) for 20 weeks. Akr1d1–/– mice had a sex-specific metabolic phenotype. At 30 weeks of age, male, but not female, Akr1d1–/– mice were more insulin tolerant and had reduced lipid accumulation in the liver and adipose tissue yet had hypertriglyceridemia and increased intramuscular triacylglycerol. This phenotype was associated with sexually dimorphic changes in bile acid metabolism and composition but without overt effects on circulating glucocorticoid levels or glucocorticoid-regulated gene expression in the liver. Male Akr1d1–/– mice were not protected against diet-induced obesity and insulin resistance. In conclusion, this study shows that AKR1D1 controls bile acid homeostasis in vivo and that altering its activity can affect insulin tolerance and lipid homeostasis in a sex-dependent manner.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition. It is tightly associated with an adverse metabolic phenotype (including obesity and type 2 diabetes) as well as with obstructive sleep apnoea (OSA) of which intermittent hypoxia is a critical component. HepaticHuman and rodent studies incorporating stable isotopes and hyperinsulinaemic euglycaemic clamp studies were performed to assess the regulation of DNL and broader metabolic phenotype by intermittent hypoxia. Cell-based studies, including pharmacological and genetic manipulation of hypoxia-inducible factors (HIF), were used to examine the underlying mechanisms.Hepatic DNL increased in response to acute intermittent hypoxia in humans, without alteration in glucose production or disposal. These observations were endorsed in a prolonged model of intermittent hypoxia in rodents using stable isotopic assessment of lipid metabolism. Changes in DNL were paralleled by increases in hepatic gene expression of acetyl CoA carboxylase 1 and fatty acid synthase. In human hepatoma cell lines, hypoxia increased both DNL and fatty acid uptake through HIF-1α and -2α dependent mechanisms.These studies provide robust evidence linking intermittent hypoxia and the regulation of DNL in both acute and sustained

Insecticide use has been linked to increased risk of non‐Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self‐reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B‐cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype‐specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20‐2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17‐2.16: FL, SLL) and DDT (OR = 1.36, 1.06‐1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (P trend = 1.7 × 10−4), chlordane (P trend = 1.0 × 10−3) and DDT (P trend = 4.2 × 10−3), however, the exposure‐response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45‐9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75‐16.53; P trend = 3.6 × 10−3). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure., What's new? Insecticides are persistent environmental pollutants that have been linked to increased risk of non‐Hodgkin lymphoma (NHL). Although NHL encompasses a heterogeneous group of malignancies, few studies have examined subtype‐specific associations for insecticide exposure. Analyzing data from population‐based case‐control studies of lymphatic cancers, the authors of this study show that lindane, chlordane, and DDT are associated with increased risk of multiple NHL subtypes. Analyses further uncovered a novel link between increased follicular lymphoma risk and pyrethrum use. None of the insecticides investigated, however, were associated with all NHL subtypes, suggesting a role for etiologic heterogeneity in pesticide exposure and NHL risk.

Exposure to phthalates is pervasive and is of concern due to associations with adverse health effects. Exposures and exposure pathways of six phthalates were investigated for 51 women aged 18-44 years in Ontario, Canada, based on measured phthalate concentrations in hand wipes and indoor media in their residences. All six phthalates had detection frequencies of 100% in air (∑

Halogenated flame retardants (HFRs) were measured in air, floor dust, and surface wipes of electronic devices (e-devices) and hands of participants in 51 Canadian homes to assess the relationship b...

Background Synthetic musk compounds are widely used as fragrances in many consumer products; however, information on human exposure and health effects is limited. Also, analytical methods for their quantification in biological matrices are limited. Objective In this study, an integrated method was developed and validated for the analysis of selected synthetic musk compounds in human serum. Method The method is based on liquid-liquid extraction (LLE), sample clean-up by solid-phase extraction (SPE), and separation and detection by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). Results The method demonstrated good recoveries (86–105%) and high sensitivity, with low method detection limits (MDLs) ranging from 0.04 to 0.17 µg/L. The method was applied to the analysis of 10 synthetic musk compounds in 40 serum samples collected from Canadian women aged 20–44 years (20 individual samples collected in 2014 and 20 pooled samples collected in 2006). The most commonly detected compound was Galaxolide (HHCB), with median concentrations of 0.59 µg/L in samples collected in 2006, and 0.34 µg/L for samples collected in 2014. Musk ketone (MK) was not detected in any of the samples collected in 2006, but was detected in 60% of the samples collected in 2014 with a median concentration of 0.29 µg/L. Tonalide (AHTN) was detected in only one sample above its MDL (0.12 µg/L). Conclusions This is the first study in Canada to report levels of synthetic musks in human. The data generated from this study has been used in risk screening assessment by Environment and Climate Change Canada and Health Canada.

OBJECTIVES: Some epidemiological studies have suggested positive associations between glyphosate use and non-Hodgkin lymphoma (NHL), but evidence is inconsistent and few studies could evaluate histological sub-types. Here, associations between glyphosate use and NHL incidence overall and by histological sub-type were evaluated in a pooled analysis of case–control studies. METHODS: The analysis included 1690 NHL cases [647 diffuse large B-cell lymphoma (DLBCL), 468 follicular lymphoma (FL), 171 small lymphocytic lymphoma (SLL), and 404 other sub-types] and 5131 controls. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for NHL overall and sub-types with self-reported ever/never, duration, frequency, and lifetime-days of glyphosate use. RESULTS: Subjects who ever used glyphosate had an excess of NHL overall (OR 1.43, 95% CI 1.11–1.83). After adjustment for other pesticides, the OR for NHL overall with "ever use" was 1.13 (95% CI 0.84–1.51), with a statistically significant association for handling glyphosate >2 days/year (OR 1.73, 95% CI 1.02–2.94, P-trend=0.2). In pesticide-adjusted sub-type analyses, the ordinal measure of lifetime-days was statistically significant (P=0.03) for SLL, and associations were elevated, but not statistically significant, for ever years or days/year of use. Handling glyphosate >2 days/year had an excess of DLBCL (OR 2.14, 95% CI 1.07–4.28; P-trend=0.2). However, as with the other sub-types, consistent patterns of association across different metrics were not observed. CONCLUSIONS: There was some limited evidence of an association between glyphosate use and NHL in this pooled analysis. Suggestive associations, especially for SLL, deserve additional attention.

Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life. To characterize exposure to phthalates during infancy and early childhood. Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA. The highest urinary concentration was for the metabolite MBP at all ages (GM: 15–32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5–15.1 ng/mL at 3 months and 1.9–32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age. Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.

ObjectivesThe causes of kidney cancer are not well understood though occupational exposures are thought to play a role. Crystalline silica is a known human carcinogen, and despite previous links with kidney disease, there have been few studies investigating its association with kidney cancer. We addressed this research gap using a population-based case-control study of Canadian men.MethodsQuestionnaire data were obtained from individuals with histologically confirmed kidney cancer, and population-based controls recruited from eight Canadian provinces (1994–1997). An industrial hygienist characterised participants’ lifetime occupational exposure, and their confidence in the assessment (possibly, probably or definitely exposed) to silica on three dimensions (intensity, frequency and duration), and cumulative exposure was estimated. Logistic regression was used to estimate ORs and 95% CIs, adjusting for potential confounders.ResultsNearly half of the 689 kidney cancer cases (49%) and 2369 controls (44%) had ever been occupationally exposed to crystalline silica. In a fully adjusted model, workers ever-exposed to silica had a slightly increased risk of kidney cancer relative to those who were unexposed (OR 1.10, 95% CI 0.92 to 1.32). Odds were modestly (and generally not statistically significantly) increased for models with duration of exposure and cumulative exposure, though exposure-response relationships were not evident.ConclusionsOur findings do not provide evidence that occupational exposure to crystalline silica increases risk of kidney cancer in men.

Background: Exposure to organophosphate ester (OPE) flame retardants and plasticizers is widespread and is of concern due to their toxicity. Objectives: To investigate relationships between and within OPE concentrations in air, dust, hands, electronic product wipes and urinary metabolites with the goal of identifying product sources and exposure pathways. Methods: Women in Toronto and Ottawa, Canada, provided a urine sample, two sets of hand wipes, access to their homes for air and dust sampling, and completed a questionnaire. OPE concentrations were obtained for air and floor dust in the bedroom (n = 51) and most used room (n = 26), hand wipes (n = 204), and surface wipes of handheld (n = 74) and non-handheld electronic devices (n = 125). All air, dust and wipe samples were analyzed for 23 OPE compounds; urine samples (n = 44) were analyzed for 8 OPE metabolites. Results: Five-8 OPEs were detected in >80% of samples depending on the sample type. OPE median concentrations in hand wipes taken 3 weeks apart were not significantly different. Palms had higher concentrations than the back of hands; both were significantly correlated. Concentrations of 9 OPEs were significantly higher in surface wipes of handheld than non-handheld electronic devices. Six OPEs in hand wipes were significantly correlated with cell phone wipes, with two to four OPEs significantly correlated with tablet, laptop and television wipes. Multiple regression models using hand wipes, cell phone wipes and dust explained 8–33% of the variation in creatinine-adjusted urinary metabolites; air concentrations did not have explanatory power. OPEs in cell phone wipes explained the greatest variation in urinary metabolites. Conclusions: Handheld electronic devices, notably cell phones, may either be sources or indicators of OPE exposure through hand-to-mouth and/or dermal uptake. Keywords: Organophosphate ester (OPE) exposure, OPE indoor concentrations, OPE exposure pathways, OPEs in electronic devices, Cell phone exposure pathway, Hand exposure pathway

Background: Arsenic is a highly prevalent environmental toxin and an established carcinogen for cancers of the skin, bladder, and lung. Emerging evidence also suggests that arsenic exposure may be a risk factor for breast and other cancers. Previous studies have been conducted in populations with endemically high levels of arsenic; however, the impact of chronic exposure to low levels is not known. Thus, the purpose of this study was to describe the arsenic exposure in Canadian adults and to evaluate the association between arsenic status and cancer risk. Methods: The Canadian Health Measures Survey (CHMS) is an ongoing, nationally representative survey that collects self-reported and objective health measures, including biomonitoring data, from participants in biennial cycles. This analysis utilized total, inorganic and organic urinary arsenic biomarkers (µg/L) from Cycles 1-5 (2007-2017) of the CHMS. Incident cancers were ascertained through a linkage to the Canadian Cancer Registry. Arsenic exposure was described using weighted percentiles, and Cox proportional hazards regression models were used to estimate the association between arsenic exposure and cancer risk (overall and site-specific). Results: This analysis included 10,000 individuals, aged 18-80. The median total urinary arsenic level was 7.5 ug/g of creatinine. Preliminary models showed that levels of inorganic arsenic exposure above the geometric mean (> 4.5 µg/L) were associated with a 3-fold increased risk of developing any cancer (HR = 3.58; 95%CI 1.63-7.85), compared to those with lower levels. Site-specific risk modelling is ongoing and preliminary results will be presented. Significance: This study found inorganic arsenic exposure may be associated with an increased risk of developing cancer. To our knowledge, this study is the first to ascertain national estimates of arsenic exposure and provide insight on the relationship between arsenic exposure and cancer risk in Canadian adults. These findings are critical for developing population-level interventions to reduce the Canadian, and global, cancer burden. Citation Format: Katherine Pullella, Vicky C. Chang, Shelley A. Harris, Anthony J. Hanley, John R. McLaughlin, Jan Lubinski, Steven A. Narod, Joanne Kotsopoulos. Examining the association between arsenic exposure and cancer risk among Canadian adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5895.

Tobacco use, of which cigarette smoking is the most common, is a global health concern and is directly linked to over 7 million premature deaths annually. Measurement of the levels of tobacco-related biomarkers in biological matrices reflects human exposure to the chemicals in tobacco products. Nicotine, nicotine metabolites, anatabine, and anabasine are specific to tobacco and nicotine containing products. However, as nicotine and its metabolites are ubiquitous in the environment, background contamination during sample preparation can occur, making the quantification of target analytes challenging. The main purpose of the present study was to examine quality control measures needed in the determination of urinary nicotine, nicotine metabolites, anatabine, and anabasine. Urine samples (n = 75) and NIST standard reference materials SRM 3671 and SRM 3672 were analysed. A one-step extraction procedure using cold acetone was used in this study, which involved no additional clean up. The blank matrices investigated included synthetic urine prepared with HPLC-grade water, synthetic urine prepared with Milli-Q water, and bovine urine. By adopting strategies for minimizing the background levels, very low detection limits for all the target analytes ranging from 0.025 ng/mL for 3-hydroxycotinine to 0.634 ng/mL for nicotine, were achieved. Recoveries ranged between 67% and 118% with RSD values below 20%. Intra-day and inter-day precisions were in the range of 1.1–11.7% and 4.8–25.2%, respectively. The levels of all target analytes were higher in daily smokers than in non-smokers, with the largest difference observed for 3-hydroxycotinine. No difference was observed in the levels of target analytes between individuals who were former smokers, who never smoked or who were exposed to environmental tobacco smoke (ETS), except for total nicotine equivalents (TNE), which was significantly higher in non-smokers exposed to environmental tobacco smoke compared with study participants who never smoked. The results obtained from SRM 3671 and SRM 3672 could inform a potential certification of additional biomarkers of exposure to tobacco products in those standard reference materials.

Background Silica and asbestos are recognized lung carcinogens. However, their role in carcinogenesis at other organs is less clear. Clearance of inhaled silica particles and asbestos fibers from the lungs may lead to translocation to sites such as the bladder where they may initiate carcinogenesis. We used data from a Canadian population-based case-control study to evaluate the associations between these workplace exposures and bladder cancer. Methods Data from a population-based case-control study were used to characterize associations between workplace exposure to silica and asbestos and bladder cancer among men. Bladder cancer cases (N = 658) and age-frequency matched controls (N = 1360) were recruited within the National Enhanced Cancer Surveillance System from eight Canadian provinces (1994–97). Exposure concentration, frequency and reliability for silica and asbestos were assigned to each job, based on lifetime occupational histories, using a combination of job-exposure profiles and expert review. Exposure was modeled as ever/never, highest attained concentration, duration (years), highest attained frequency (% worktime) and cumulative exposure. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using adjusted logistic regression. Results A modest (approximately 20%) increase in bladder cancer risk was found for ever having been exposed to silica, highest attained concentration and frequency of exposure but this increase was not statistically significant. Relative to unexposed, the odds of bladder cancer were 1.41 (95%CI: 1.01–1.98) times higher among men exposed to silica at work for ≥27 years. For asbestos, relative to unexposed, an increased risk of bladder cancer was observed for those first exposed ≥20 years ago (OR:2.04, 95%CI:1.25–3.34), those with a frequency of exposure of 5–30% of worktime (OR:1.45, 95%CI:1.06–1.98), and for those with Conclusions Our results indicate a slight increase in risk of bladder cancer with exposure to silica and asbestos, suggesting that the effects of these agents are broader than currently recognized. The findings from this study inform evidence-based action to enhance cancer prevention efforts, particularly for workers in industries with regular exposure.

Passive air samplers (PAS) were evaluated for measuring indoor concentrations of phthalates, novel brominated flame retardants (N-BFRs), polybrominated diphenyl ethers (PBDEs), and organophosphate esters (OPEs). Sampling rates were obtained from a 50-day calibration study for two newly introduced PAS, polydimethylsiloxane (PDMS) or silicone rubber PAS (one with and one without a coating of styrene divinyl benzene co-polymer, XAD) and the commonly used polyurethane foam (PUF) PAS. Average sampling rates normalized to PAS surface area were 1.5 ± 1.1 m3 day−1 dm−2 for both unsheltered PDMS and XAD-PDMS, and 0.90 m3 ± 0.6 day−1dm−2 for partially sheltered PUF. These values were derived based on the compound-specific sampling rates measured here and in the literature for the PAS tested, to reasonably account for site-specific variability of sampling rates. PDMS and PUF were co-deployed for three weeks in 51 homes located in Ottawa and Toronto, Canada. Duplicate PUF and PDMS samplers gave concentrations within 10% of each other. PDMS and PUF-derived air concentrations were not statistically different for gas-phase compounds. PUF had a higher detection of particle-phase compounds such as some OPEs. Phthalate and OPE air concentrations were ∼100 times higher than those of N-BFRs and PBDEs. Concentrations were not systematically related to PM10, temperature or relative humidity. We conclude that both PAS provide replicable estimates of indoor concentrations of these targeted semi-volatile organic compounds (SVOCs) over a three-week deployment period. However, PUF is advantageous for collecting a wider range of compounds including those in the particle phase.

Objective Previous studies considered the role of occupational causes in kidney cancer but were limited by small sample sizes and imprecise exposure assessment. This study examined the relationship between occupational exposure to asbestos and the risk of kidney cancer across a range of jobs in a large, population-based case-control study in Canada. Methods Data were from the case-control component of the National Enhanced Cancer Surveillance System, a study conducted between 1994 and 1997 in eight Canadian provinces. Male kidney cancer cases, histologically confirmed, and controls completed questionnaires on socio-demographics, anthropometry, diet, smoking, secondhand smoke exposure, and physical activity. Occupational histories were also collected, including each job held for at least 1 year since the age of 18. Occupational hygienists, blinded to case status, assigned exposure to asbestos, considering intensity, frequency, and probability of exposure (each 3-point scales). Logistic regression was used to estimate the odds of kidney cancer in exposed participants (defined using three metrics) compared to those without asbestos exposure. Results There were 712 cases and 2454 controls in these analyses. Ever-exposure to asbestos was associated with 20% increased odds of kidney cancer compared to unexposed workers (OR 1.2, 95% confidence interval 1.0–1.4 when including possibly exposed workers). A small increase in risk was observed with cumulative exposure, while increasing intensity of exposure was related to increased odds of kidney cancer. Conclusions This study found some evidence for an association between occupational exposure to asbestos and kidney cancer. Higher intensity of exposure to asbestos had the strongest relationship with kidney cancer risk.

Polybrominated diphenyl ether (PBDE) flame retardants contaminate the food supply yet health effects are uncertain. A global PBDE database was developed to improve diet and disease risk assessments. Congener-specific data from 2002 to 2015 were extracted from 86 articles into a source database representing 32 countries. Geometric mean PBDE concentrations for foods and supplements were derived for 11 congeners individually and combined, and used to calculate means for 27 dietary groups (pg/g ww). Dark or oily fish had the highest data availability, followed by shellfish, eggs, dairy products and dairy fats. Data were less available for white or lean fish, red meat, poultry meat, processed meats, fish oil supplements; 17 groups had very limited data. At the group level, mean ∑11PBDE was extremely high for fish oil supplements (13,862 pg/g) and high for most aquatic groups (462–837 pg/g), poultry liver, poultry fat (1045–1860 pg/g). Moderate groups included white or lean fish, poultry meat, poultry skin, eggs, baked products, red meat fat, red meat liver (115–414 pg/g). Dairy and plant groups had low PBDE concentrations. ∑11PBDE variability was high within most aquatic groups. This database supports assessment of dietary PBDE in multiple jurisdictions and identifies important sources for dietary tool inclusion and analyses.

As there are no well‐established modifiable risk factors for prostate cancer, further evidence is needed on possible factors such as occupation. Our study uses one of the largest Canadian worker cohorts to examine occupation, industry, and prostate cancer and to assess patterns of prostate cancer rates. The Canadian Census Health and Environment Cohort (CanCHEC) was established by linking the 1991 Canadian Census Cohort to the Canadian Cancer Database (1969–2010), Canadian Mortality Database (1991–2011), and Tax Summary Files (1981–2011). A total of 37,695 prostate cancer cases were identified in men aged 25–74 based on age at diagnosis. Cox proportional hazards models were used to estimate hazards ratios and 95% confidence intervals. In men aged 25–74 years, elevated risks were observed in the following occupations: senior management (HR = 1.12, 95% CI: 1.04–1.20); office and administration (HR = 1.19, 95% CI: 1.11–1.27); finance services (HR = 1.09, 95% CI: 1.04–1.14); education (HR = 1.05, 95% CI: 1.00–1.11); agriculture and farm management (HR = 1.12, 95% CI: 1.06–1.17); farm work (HR = 1.11, 95% CI: 1.01–1.21); construction managers (HR = 1.07, 95% CI: 1.01–1.14); firefighting (HR = 1.17, 95% CI: 1.01–1.36); and police work (HR = 1.22, 95% CI: 1.09–1.36). Decreased risks were observed across other construction and transportation occupations. Results by industry were consistent with occupation results. Associations were identified for white‐collar, agriculture, protective services, construction, and transportation occupations. These findings emphasize the need for further study of job‐related exposures and the potential influence of nonoccupational factors such as screening practices.

Background: Arsenic is an established carcinogen for cancers of the skin, bladder and lungs; it is also the most prevalent environmental toxin, resulting in all Canadians being exposed to some extent. In a recent prospective study of a low-exposure population, our team found that women in the highest quartile of circulating arsenic had a significant 13-fold increased risk of developing breast cancer, compared to the lowest quartile. This suggests that even at low-doses, arsenic may be an important risk factor for breast, and potentially other cancers not previously recognized. To date, the sources of arsenic in Canada, a low-exposure population, are unclear. Objectives: To describe the status of arsenic exposure, identify the key predictors of arsenic status, and evaluate the relationship between arsenic exposure and cancer risk within the Canadian population. Methods: Using data from Cycles 1-5 (2007-2017) of the Canadian Health Measures Survey (CHMS), exposure data (e.g., diet, water), demographic information, and urinary arsenic biomarkers will be analyzed. The CHMS is an ongoing, nationally representative survey, collecting objective health measures and food intake information from participants in biennial cycles. Data will be described using weighted percentages or means, and arsenic levels (total and speciated urinary arsenic metabolite concentrations) will be reported by percentile. Weighted multivariate regression models will be used to identify predictors of total urinary arsenic. Linkage to the Canadian Cancer Registry will be performed to ascertain incident cancers, and Cox proportional hazards regression used to estimate the relationship between arsenic status and cancer risk (total and site-specific). Results: This analysis included 15,700 individuals, aged 18-80. The median total urinary arsenic level was 7.5 ug/g of creatinine. Significant predictors of total urinary arsenic levels were found to be weekly intake of fish and seafood (β= 0.3, 95%CI 0.27,0.33, P < 0.001), grains (β=-0.02, 95%CI -0.02, -0.01, P< 0.001) and consumption of well and/or cistern water (β = 0.13, 95%CI 0.04, 0.22, P=0.005). Linkage and data analysis are ongoing. Impact: This work is the first to ascertain national exposure estimates to an environmental carcinogen. Fish, seafood, grains, and consumption of well and/or cistern water represent significant predictors of total urinary arsenic levels in Canada. Ultimately, this information is needed to develop critical population-level intervention strategies to reduce the Canadian, and global burden of cancer. Citation Format: Katherine Pullella, Shelley A. Harris, John R. McLaughlin, Jan Lubinski, Steven A. Narod, Joanne Kotsopoulos. Evaluating the relationship between arsenic exposure and cancer risk in Canada [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 857.

Background Studies have demonstrated an association between phthalate exposure and childhood asthma, although results have been inconsistent. No epidemiological studies have examined exposure during the first year of life. Objective To investigate the association between phthalate exposures in the home environment during the first year of life, and subsequent development of childhood asthma and related symptoms. Methods This study used a case-cohort design including 436 randomly selected children and all additional cases of asthma at 5 years (ntotal = 129) and recurrent wheeze between 2 and 5 years (ntotal = 332) within the CHILD Cohort Study, a general population Canadian birth cohort of 3455 children. Phthalate exposure was assessed using house dust samples collected during a standardized home visit when children were 3-4 months of age. All children were assessed by specialist clinicians for asthma and allergy at 1, 3 and 5 years. Logistic regression was used to assess the association between exposure to five phthalates and asthma diagnosis at 5 years, and recurrent wheeze between 2 and 5 years, with further stratification by wheeze subtypes (late onset, persistent, transient) based on the timing of onset and persistence of wheeze symptoms. Results Di(2-ethylhexyl) phthalate (DEHP) had the highest concentration in dust (mediansubcohort = 217 μg/g), followed by benzyl butyl phthalate (BzBP) (20 μg/g). A nearly four-fold increase in risk of developing asthma was associated with the highest concentration quartile of DEHP (OR = 3.92, 95% CI: 1.87–8.24) including a positive dose-response relationship. A two-fold increase in risk of recurrent wheeze was observed across all quartiles compared to the lowest quartile of DEHP concentrations. Compared to other wheeze subtypes, stronger associations for DEHP were observed with the late onset wheezing subtype, while stronger associations for di-iso-butyl phthalate (DiBP) and BzBP were observed with the transient subtype. Discussion DEHP exposure at 3-4 months, at concentrations lower than other studies that reported an association, were associated with increased risks of asthma and recurrent wheeze among children at 5 years. These findings suggest the need to assess whether more stringent regulations are required to protect children's health, which can be informed by future work exploring the main sources of DEHP exposure.

Background The etiology of prostate cancer continues to be poorly understood, including the role of occupation. Past Canadian studies have not been able to thoroughly examine prostate cancer by occupation with detailed information on individual level factors. Methods Occupation, industry and prostate cancer were examined using data from the National Enhanced Cancer Surveillance System, a large population-based case-control study conducted across eight Canadian provinces from 1994 to 1997. This analysis included 1737 incident cases and 1803 controls aged 50 to 79 years. Lifetime occupational histories were used to group individuals by occupation and industry employment. Odds ratios and 95% confidence intervals were calculated and adjustments were made for known and possible risk factors. Results By occupation, elevated risks were observed in farming and farm management (OR=1.37, 95% CI 1.02–1.84), armed forces (OR=1.33, 95% CI 1.06-1.65) and legal work (OR=2.58, 95% CI 1.05–6.35). Elevated risks were also observed in office work (OR=1.20, 95% CI 1.00–1.43) and plumbing (OR=1.77, 95% CI 1.07–2.93) and with ≥10 years duration of employment. Decreased risks were observed in senior management (OR=0.65, 95% CI 0.46–0.91), construction management (OR=0.69, 95% CI 0.50–0.94) and travel work (OR=0.37, 95% CI 0.16–0.88). Industry results were similar to occupation results, except for an elevated risk in forestry/logging (OR=1.54, 95% CI 1.06–2.25) and a decreased risk in primary metal products (OR=0.70, 95% CI 0.51–0.96). Conclusion This study presents associations between occupation, industry and prostate cancer, while accounting for individual level factors. Further research is needed on potential job-specific exposures and screening behaviours.

The incidence of breast cancer is on a rise worldwide; it is a disease having a complex etiology. Besides genetics, environmental and other lifestyle factors play a role in the development of the disease. There has been a keen interest in studying associations between breast cancer and exposures to emerging environmental chemicals, which mimic estrogens or influence estrogen levels and signaling in the human body. The common consequence of an endocrine disrupting chemical exposure is that it may have an impact on breast cancer etiology by stimulating formation as well as progression of breast cancer. Exposures to selected emerging environmental contaminants such as alkylphenols (APs), bisphenol A (BPA), parabens, perfluoroalkyl substances (PFASs), phthalates, polybrominated diphenyl ethers (PBDEs), synthetic musks and triclosan, and their probable role in breast cancer development are reviewed. Studies evaluated include the experimental in vitro and in vivo studies as well as human population based studies. In vitro and in vivo evidences indicate that a number of emerging environmental contaminants may play a role in the initiation and/or progression of breast cancer. Although exposures have been assessed in some human populations, breast and other cancer risks associated with these exposures are largely unknown. Efforts should be focussed on the evaluation of these environmental exposures in human populations and their interactions with each other and other genetic and lifestyle risk factors.

Purpose The purpose of this study was to investigate associations between pesticide exposures and risk of Hodgkin lymphoma (HL) using data from the North American Pooled Project (NAPP). Methods Three population-based studies conducted in Kansas, Nebraska, and six Canadian provinces (HL = 507, Controls = 3886) were pooled to estimate odds ratios and 95% confidence intervals for single (never/ever) and multiple (0, 1, 2–4, ≥ 5) pesticides used, duration (years) and, for select pesticides, frequency (days/year) using adjusted logistic regression models. An age-stratified analysis (≤ 40/ > 40 years) was conducted when numbers were sufficient. Results In an analysis of 26 individual pesticides, ever use of terbufos was significantly associated with HL (OR: 2.53, 95% CI 1.04–6.17). In age-stratified analyses, associations were stronger among those ≤ 40 years of age. No significant associations were noted among those > 40 years old; however, HL cases ≤ 40 were three times more likely to report ever using dimethoate (OR: 3.76 95% CI 1.02–33.84) and almost twice as likely to have ever used malathion (OR: 1.86 95% CI 1.00–3.47). Those ≤ 40 years of age reporting use of 5 + organophosphate insecticides had triple the odds of HL (OR: 3.00 95% CI 1.28–7.03). Longer duration of use of 2,4-D, ≥ 6 vs. 0 years, was associated with elevated odds of HL (OR: 2.59 95% CI 1.34–4.97). Conclusion In the NAPP, insecticide use may increase the risk of HL, but results are based on small numbers.

Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled × years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40-7.23) for ≤10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend = 0.01). For captan, ≤17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend = 0.01). An increasing trend (ptrend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many applications; however, certain PBDE congeners are persistent, bioaccumulative, and toxic to both humans and the environment. PBDEs have been found in human specimens, and a variety of analytical techniques have been used for their determination in biological matrixes. Nevertheless, obtaining a relatively clean analytical blank sample during PBDE analysis is a big challenge because of the ubiquitous nature of these compounds. Thus, the present study was conducted to compare the PBDE background levels associated with the three most commonly used extraction techniques: liquid–liquid extraction (LLE), SPE, and accelerated solvent extraction (ASE). Conventionally used blank matrixes (HPLC grade water, Milli-Q water, and air) were spiked with internal standards and extracted using LLE, SPE, or ASE. The extracts were analyzed by GC/electron ionization-tandem MS. The ASE method achieved the lowest background levels for nearly all the PBDE congeners analyzed, which may be attributed to the stainless steel and closed-vessel nature of the ASE cells.

Occupational magnetic field (MF) exposure has been suggested as a risk factor for breast cancer in both men and women. Due to the rarity of this disease in men, most epidemiologic studies investigating this relationship have been limited by small sample sizes. Herein, associations of several measures of occupational MF exposure with breast cancer in men were investigated using data from the population‐based case–control component of the Canadian National Enhanced Cancer Surveillance System. Lifetime job histories were provided by 115 cases and 570 controls. Average MF exposure of individual jobs was classified into three categories (

Organophosphate esters (OPEs) are high-production volume chemicals. Use of OPEs has largely increased since the phase-out/ban of polybrominated diphenyl ethers (PBDEs). The ubiquitous occurrence of OPEs, in higher concentrations in abiotic matrices than brominated flame retardants (BFRs), is a concern because several of the OPEs have been linked to adverse health effects. In this study, urinary metabolites of OPEs were measured in a subset of a population-based sample of women of child bearing age recruited in Ontario, and associations between serum lipid levels and urinary concentrations of OPE metabolites were evaluated. Urine samples (n = 120) were extracted using automated solid phase extraction and analysed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Diphenyl phosphate (DPHP), bis(2-chloropropyl) phosphate (BCIPP) and bis(1,3-dichloro-2 propyl) phosphate (BDCIPP) were detected with frequencies of 100%, 76% and 75% at median concentrations of 13.8 ng/mL, 0.5 ng/mL and 1.8 ng/mL, respectively. Bis(2-chloroethyl) hydrogen phosphate (BCEP) and di-cresyl phosphate (DCP; mixture of 3 isomers) were detected in 52% and 42% of the samples, respectively. Detected at lower frequencies were 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 29%), bis-2(butoxyethyl) phosphate (BBOEP, 11%), and desbutyl-tris-(2-butoxy-ethyl) phosphate (desbutyl TBOEP, 9%). Using multiple regression model, a negative statistically significant correlation was observed between BCEP and cholesterol (p = 0.04), as well as BCEP and total lipid (p = 0.04). Whereas BCIPP was positively and significantly correlated with cholesterol (p = 0.003) and LDL (p = 0.001). Additional work to further explore these relationships and to evaluate more recently identified OPE metabolites is warranted.

Historically, organophosphate and carbamate insecticides have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associatio...

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants commonly used in a wide range of household products and electronic devices. Some PBDE congeners have endocrine-disrupting prop...

Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14–1.81) compared with never users. Categories using tertiles of duration (< 4 yrs., 4–12 yrs., and > 12yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR < 4vsUnex = 1.33 (0.88, 2.03), OR4–12vsUnex = 1.42 (1.02, 1.96), OR > 12vsUnex = 1.55 (1.05, 2.28, p-trend < 0.01)). In addition, malathion use was statistically significantly associated with FL (OR = 1.58; 95% CI: 1.11–2.27) and DLBCL (OR = 1.61; 95% CI: 1.16–2.22) while there were no apparent associations with SLL or other subtypes, the p-value for heterogeneity across subtypes, however, was not significant. These results support previous studies suggesting an association between insecticide use and NHL overall, and provide new information on associations with NHL subtypes.

IntroductionCertain subject behaviours and characteristics increase the risk of some cancer types (e.g., obesity, alcohol intake) while others reduce cancer risk (e.g., physical activity). In 2007, the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) published recommendations to reduce cancer risk related to these behaviours. Objectives and ApproachThe objective is to examine the association between self-reported behaviour consistent with WCRF/AICR recommendations for body fatness, physical activity, vegetable/fruit consumption, and alcohol intake and the risk of all cancers combined and specific cancer types. The study cohort, comprised of the Canadian Community Health Survey (CCHS) Ontario sample, will be linked with health administrative databases, including the Ontario Cancer Registry to determine cancer outcomes. Individuals will be assessed for behaviours consistent with WCRF/AICR recommendations based on their responses to CCHS questions and the association of these behaviours with cancer risk will be explored using multivariable Cox proportional hazard regression models. ResultsTo detect a log hazard ratio of 1.10 (where a=0.05, power=0.80, proportion of the sample assigned to the exposure group=0.25 and R2=0.20), a sample size of 4,538 is required. Based on the number of records in the CCHS data frame (159,474) and an assumption that the CCHS sample experiences cancer incidence at a similar rate to the rest of the Ontario population, we expect to have 5,000 cancer cases for these analyses. Upon completion of the analysis, we will report hazard ratios that estimate the difference in cancer risk between individuals reporting behaviour consistent with the WCRF/AICR recommendations and those reporting behaviour not consistent with the recommendations. Conclusion/ImplicationsWCRF/AICR recommendations were developed as the basis for primary cancer prevention, both for individuals and population-wide policies and programs. The current study will quantify the difference in overall cancer risk between individuals who do and do not adhere to selected WCRF/AICR recommendations for the first time in a Canadian population.

Introduction Kidney cancer is the fifth most common incident cancer in Canadian men. Diesel and gasoline exhausts are common workplace exposures that have been examined as risk factors for non-lung cancer sites, including the kidney, but limitations in exposure assessment methods have contributed to inconsistent findings. The objective of this study was to assess the relationship between occupational gasoline and diesel engine exhausts and the risk of kidney cancer in men. Methods The National Enhanced Cancer Surveillance System (NECSS) is a Canadian population-based case–control study conducted in 1994–1997. Incident kidney cancer cases were identified using provincial registries, while the control series was identified through random-digit dialing, or provincial administrative databases. Self-reported questionnaires were used to obtain information on lifetime occupational history and cancer risk factors. Two hygienists, blinded to case status, coded occupational histories for diesel and gasoline exhaust exposures using concentration, frequency, duration, and reliability. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) separately by exhaust type. The separate and combined impacts of both engine exhausts were also examined. ORs were adjusted for age, province, body mass index, occupational secondhand smoke exposure, and education. Results Of the kidney cancer cases (n = 712), 372 (52%) had exposure to both exhausts at some point, and 984 (40%) of the controls (n = 2457) were ever exposed. Workers who had ever been exposed to engine exhausts were more likely to have kidney cancer than those who were never exposed (OR diesel = 1.23, 95% CI = 0.99–1.53; OR gasoline = 1.51, 95% CI = 1.23–1.86). Exposure to gasoline exhaust was consistently associated with kidney cancer in a dose–response manner (P value for trends in highest attained and cumulative exposure both

Goodson, William H. et al., © The Author 2015. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology., We gratefully acknowledge the support of the National Institute of Health-National Institute of Environmental Health Sciences (NIEHS) conference grant travel support (R13ES023276); Glenn Rice, Office of Research and Development, United States Environmental Protection Agency, Cincinnati, OH, USA also deserves thanks for his thoughtful feedback and inputs on the manuscript; William H.Goodson III was supported by the California Breast Cancer Research Program, Clarence Heller Foundation and California Pacific Medical Center Foundation; Abdul M.Ali would like to acknowledge the financial support of the University of Sultan Zainal Abidin, Malaysia; Ahmed Lasfar was supported by an award from the Rutgers Cancer Institute of New Jersey; Ann-Karin Olsen and Gunnar Brunborg were supported by the Research Council of Norway (RCN) through its Centres of Excellence funding scheme (223268/F50), Amancio Carnero’s lab was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0306-2012); Matilde E. Lleonart was supported by a trienal project grant PI12/01104 and by project CP03/00101 for personal support. Amaya Azqueta would like to thank the Ministerio de Educacion y Ciencia (‘Juande la Cierva’ programme, 2009) of the Spanish Government for personal support; Amedeo Amedei was supported by the Italian Ministry of University and Research (2009FZZ4XM_002), and the University of Florence (ex60%2012); Andrew R.Collins was supported by the University of Oslo; Annamaria Colacci was supported by the Emilia-Romagna Region - Project ‘Supersite’ in Italy; Carolyn Baglole was supported by a salary award from the Fonds de recherche du Quebec-Sante (FRQ-S); Chiara Mondello’s laboratory is supported by Fondazione Cariplo in Milan, Italy (grant n. 2011-0370); Christian C.Naus holds a Canada Research Chair; Clement Yedjou was supported by a grant from the National Institutes of Health (NIH-NIMHD grant no. G12MD007581); Daniel C.Koch is supported by the Burroughs Wellcome Fund Postdoctoral Enrichment Award and the Tumor Biology Training grant: NIH T32CA09151; Dean W. Felsher would like to acknowledge the support of United States Department of Health and Human Services, NIH grants (R01 CA170378 PQ22, R01 CA184384, U54 CA149145, U54 CA151459, P50 CA114747 and R21 CA169964); Emilio Rojas would like to thank CONACyT support 152473, Ezio Laconi was supported by AIRC (Italian Association for Cancer Research, grant no. IG 14640) and by the Sardinian Regional Government (RAS); Eun-Yi Moon was supported by grants from the Public Problem-Solving Program (NRF-015M3C8A6A06014500) and Nuclear R&D Program (#2013M2B2A9A03051296 and 2010-0018545) through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology (MEST) in Korea; Fahd Al-Mulla was supported by the Kuwait Foundation for the Advancement of Sciences (2011-1302-06); Ferdinando Chiaradonna is supported by SysBioNet, a grant for the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI) and by AIRC (Associazione Italiana Ricerca sul Cancro; IG 15364); Francis L.Martin acknowledges funding from Rosemere Cancer Foundation; he also thanks Lancashire Teaching Hospitals NHS trust and the patients who have facilitated the studies he has undertaken over the course of the last 10 years; Gary S.Goldberg would like to acknowledge the support of the New Jersey Health Foundation; Gloria M.Calaf was supported by Fondo Nacional de Ciencia y Tecnología (FONDECYT), Ministerio de Educación de Chile (MINEDUC), Universidad de Tarapacá (UTA); Gudrun Koppen was supported by the Flemish Institute for Technological Research (VITO), Belgium; Hemad Yasaei was supported from a triennial project grant (Strategic Award) from the National Centre for the Replacement, Refinement and Reduction (NC3Rs) of animals in research (NC.K500045.1 and G0800697); Hiroshi Kondoh was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Science and Technology Agency and by JST, CREST; Hsue-Yin Hsu was supported by the Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002); Hyun Ho Park was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (2012R1A2A2A01010870) and a grant from the Korea Healthcare Technology R&D project, Ministry of Health and Welfare, Republic of Korea (HI13C1449); Igor Koturbash is supported by the UAMS/NIH Clinical and Translational Science Award (UL1TR000039 and KL2TR000063) and the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000; Jan Vondráček acknowledges funding from the Czech Science Foundation (13-07711S); Jesse Roman thanks the NIH for their support (CA116812), John Pierce Wise Sr. and Sandra S.Wise were supported by National Institute of Environmental Health Sciences (ES016893 to J.P.W.) and the Maine Center for Toxicology and Environmental Health; Jonathan Whitfield acknowledges support from the FERO Foundation in Barcelona, Spain; Joseph Christopher is funded by Cancer Research UK and the International Journal of Experimental Pathology; Julia Kravchenko is supported by a philanthropic donation by Fred and Alice Stanback; Jun Sun is supported by a Swim Across America Cancer Research Award; Karine A.Cohen-Solal is supported by a research scholar grant from the American Cancer Society (116683-RSG-09-087-01-TBE); Laetitia Gonzalez received a postdoctoral fellowship from the Fund for Scientific Research–Flanders (FWO-Vlaanderen) and support by an InterUniversity Attraction Pole grant (IAP-P7-07); Laura Soucek is supported by grant #CP10/00656 from the Miguel Servet Research Contract Program and acknowledges support from the FERO Foundation in Barcelona, Spain; Liang-Tzung Lin was supported by funding from the Taipei Medical University (TMU101-AE3-Y19); Linda Gulliver is supported by a Genesis Oncology Trust (NZ) Professional Development Grant, and the Faculty of Medicine, University of Otago, Dunedin, New Zealand; Louis Vermeulen is supported by a Fellowship of the Dutch Cancer Society (KWF, UVA2011-4969) and a grant from the AICR (14–1164); Mahara Valverde would like to thank CONACyT support 153781; Masoud H. Manjili was supported by the office of the Assistant Secretary of Defense for Health Affairs (USA) through the Breast Cancer Research Program under Award No. W81XWH-14-1-0087 Neetu Singh was supported by grant #SR/FT/LS-063/2008 from the Department of Science and Technology, Government of India; Nicole Kleinstreuer is supported by NIEHS contracts (N01-ES 35504 and HHSN27320140003C); P.K. Krishnakumar is supported by the Funding (No. T.K. 11-0629) of King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia; Paola A.Marignani is supported by the Dalhousie Medical Research Foundation, The Beatrice Hunter Cancer Institute and CIHR and the Nova Scotia Lung Association; Paul Dent is the holder of the Universal Inc.Chair in Signal Transduction Research and is supported with funds from PHS grants from the NIH (R01-CA141704, R01-CA150214, R01-DK52825 and R01-CA61774); Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, and by the Czech Science Foundation projects P301/12/1686 and 15-03834Y; Po Sing Leung was supported by the Health and Medical Research Fund of Food and Health Bureau, Hong Kong Special Administrative Region, Ref. No: 10110021; Qiang Cheng was supported in part by grant NSF IIS-1218712; R. Brooks Robey is supported by the United States Department of Veterans Affairs; Rabindra Roy was supported by United States Public Health Service Grants (RO1 CA92306, RO1 CA92306-S1 and RO1 CA113447); Rafaela Andrade-Vieira is supported by the Beatrice Hunter Cancer Research Institute and the Nova Scotia Health Research Foundation, Renza Vento was partially funded by European Regional Development Fund, European Territorial Cooperation 2007–13 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007–13) and grants from the Italian Ministry of Education, University and Research (MIUR) ex-60%, 2007; Riccardo Di Fiore was a recipient of fellowship granted by European Regional Development Fund, European Territorial Cooperation 2007–2013 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007–2013); Rita Dornetshuber-Fleiss was supported by the Austrian Science Fund (FWF, project number T 451-B18) and the Johanna Mahlke, geb.-Obermann-Stiftung; Roberta Palorini is supported by a SysBioNet fellowship; Roslida Abd Hamid is supported by the Ministry of Education, Malaysia-Exploratory Research Grant Scheme-Project no: ERGS/1-2013/5527165; Sabine A.S.Langie is the beneficiary of a postdoctoral grant from the AXA Research Fund and the Cefic-LRI Innovative Science Award 2013; Sakina Eltom is supported by NIH grant SC1CA153326; Samira A.Brooks was supported by National Research Service Award (T32 ES007126) from the National Institute of Environmental Health Sciences and the HHMI Translational Medicine Fellowship; Sandra Ryeom was supported by The Garrett B. Smith Foundation and the TedDriven Foundation; Thierry Massfelder was supported by the Institut National de la Santé et de la Recherche Médicale INSERM and Université de Strasbourg; Thomas Sanderson is supported by the Canadian Institutes of Health Research (CIHR; MOP-115019), the Natural Sciences and Engineering Council of Canada (NSERC; 313313) and the California Breast Cancer Research Program (CBCRP; 17UB-8703); Tiziana Guarnieri is supported by a grant from Fundamental Oriented Research (RFO) to the Alma Mater Studiorum University of Bologna, Bologna, Italy and thanks the Fondazione Cassa di Risparmio di Bologna and the Fondazione Banca del Monte di Bologna e Ravenna for supporting the Center for Applied Biomedical Research, S.Orsola-Malpighi University Hospital, Bologna, Italy; W.Kimryn Rathmell is supported by the V Foundation for Cancer Research and the American Cancer Society; William K.Decker was supported in part by grant RP110545 from the Cancer Prevention Research Institute of Texas; William H.Bisson was supported with funding from the NIH P30 ES000210; Yon Rojanasakul was supported with NIH grant R01-ES022968; Zhenbang Chen is supported by NIH grants (MD004038, CA163069 and MD007593); Zhiwei Hu is grateful for the grant support from an institutional start-up fund from The Ohio State University College of Medicine and The OSU James Comprehensive Cancer Center (OSUCCC) and a Seed Award from the OSUCCC Translational Therapeutics Program.

Objectives We conducted a systematic review and meta-analysis to evaluate potential associations between firefighting and police occupations, and prostate cancer incidence and mortality. Methods Original epidemiological studies published from 1980 to 2017 were identified through PubMed and Web of Science. Studies were included if they contained specific job titles for ever/never firefighting and police work and associated prostate cancer risk estimates with 95% confidence intervals (CI). Study quality was assessed using a 20-point checklist. Prostate cancer meta-risk estimates (mRE) and corresponding 95% CIs were calculated for firefighting and police work separately and by various study characteristics using random effects models. Between-study heterogeneity was evaluated using the I2 score. Publication bias was assessed using Begg’s and Egger’s tests. Results A total of 26 firefighter and 12 police studies were included in the meta-analysis, with quality assessment scores ranging from 7 to 19 points. For firefighter studies, the prostate cancer incidence mRE was 1.17 (95% CI = 1.08–1.28, I2 = 72%) and the mortality mRE was 1.12 (95% CI = 0.92–1.36, I2 = 50%). The mRE for police incidence studies was 1.14 (95% CI = 1.02–1.28; I2 = 33%); for mortality studies, the mRE was 1.08 (95% CI = 0.80–1.45; I2 = 0%). By study design, mREs for both firefighter and police studies were similar to estimates of incidence and mortality. Conclusion Small excess risks of prostate cancer were observed from firefighter studies with moderate to substantial heterogeneity and a relatively small number of police studies, respectively. There is a need for further studies to examine police occupations and to assess unique and shared exposures in firefighting and police work. Electronic supplementary material The online version of this article (10.1186/s12940-017-0336-z) contains supplementary material, which is available to authorized users.

Background Isoflavones and lignans (phytoestrogens) are dietary components with potential anticarcinogenic effects. Although the intake of isoflavones and lignans may affect breast cancer treatment and prognosis—and associations may differ by menopausal status—postdiagnosis intake data are limited. Objective We aimed to describe postdiagnosis isoflavone and lignan intake in newly diagnosed breast cancer patients, examine differences by menopausal status and phytoestrogen type, and inform the assessment of diet and survival in future prognostic studies. Methods Our cross-sectional study included 278 women aged 25–74 y, diagnosed with pathologically confirmed breast cancer in April–May 2010 and identified using the Ontario Cancer Registry. Intake in the previous 2 mo was assessed using questionnaires listing 17 soy and 3 high-lignan foods (flaxseed, flaxseed bread, sesame seeds), completed 71 d after breast cancer diagnosis, on average. Food consumption by menopausal status was examined. Geometric mean and median phytoestrogen intakes were estimated among all patients and in consumers only; differences by menopausal status and phytoestrogen type were assessed. Results Among all patients, foods were similarly consumed by menopausal status and isoflavone intakes were low (median: 56 µg/d). Consumers (n = 219) had higher intakes (median isoflavones: 1808 µg/d); 7% of isoflavone and 21% of lignan consumers had intakes ≥10 mg/d. Intakes were higher in premenopausal than in postmenopausal consumers, particularly for lignans, but were not significantly different (median lignans: 4375 compared with 1863 µg/d; P = 0.07). Lignans were significantly higher than isoflavones among most consumers (postmenopausal means: 746 compared with 100 µg/d; P

Prostate cancer is one of the most commonly diagnosed cancers in men and further evidence is needed on preventable risk factors. This study investigated the relationship between prostate cancer risk and occupation using a large Canadian cohort. The Canadian Census Health and Environment Cohort was established by linking the 1991 Canadian Census Cohort to the Canadian Cancer Database (1969–2010), Canadian Mortality Database (1991–2011) and the Tax Summary Files (1981–2011). A total of 37 695 prostate cancer cases were identified based on age at diagnosis. Cox proportional hazards models were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). Overall, age standardised prostate cancer rates were observed to be highest in white collar workers and lowest in construction/transportation workers. In men aged 50–74 years, elevated risks were observed in agriculture management (HR=1.11, 95% CI 1.06–1.17), farm work (HR=1.12, 95% CI 1.02–1.23), firefighting (HR=1.16, 95% CI 1.00–1.35), military (HR=1.14, 95% CI 1.00–1.32), police (HR=1.28, 95% CI 1.14–1.42), senior management (HR=1.09, 95% CI 1.02–1.17), office (HR=1.16, 95% CI 1.08–1.24), and finance (HR=1.08, 95% CI 1.03–1.13). Similar findings were observed in men aged 25–49 years, with additional elevated risks in office management (HR=1.19, 95% CI 1.11–1.27) and education (HR=1.05, 95% CI 1.00–1.11). Decreased risks were observed in construction and transportation occupations in both age groups. Findings across agriculture and protective services were consistent with previous studies. Some findings, particularly among management occupations, may be due to screening. Further investigation is needed on job-specific exposures with better understanding on differences in rates across occupations.

Objectives The objective of this study was to investigate whether occupational gasoline and/or diesel exhaust exposure contribute to kidney cancer risk. Methods The National Enhanced Cancer Surveillance System is a population-based case-control study conducted from 1994–1997 in Canada. Incident kidney cancer cases were identified using provincial registries, while the control series were identified through random digit dialling, or provincial datasets. Self-reported questionnaires obtained information on lifetime occupational history and cancer risk factors. Hygienists coded occupational histories for diesel and gasoline exhaust exposures using concentration, frequency, duration and reliability. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals separately by exhaust type. Models were adjusted for age, province, BMI, and cigarette smoking. Results Complete occupational data were available for 652 cases and 2368 controls. The majority of workers had been exposed to diesel (53%) or gasoline (55%) exhausts, respectively; most exposures were at low concentrations. Workers who had ever been exposed were significantly more likely to have kidney cancer than those who were never exposed (OR diesel: 1.4;1.1–1.6, OR gasoline: 1.7;1.4–2.1). When examining duration of exposure and tertiles of cumulative exposure, diesel and gasoline exposures were both linked to a significantly increased risk of kidney cancer (p Conclusions This study provides evidence that occupational gasoline and to a lesser extent, diesel exhaust exposure increases the risk of kidney cancer.

Objectives Although epidemiological studies have generally shown inconsistent findings for prostate cancer risk and occupation, some associations with firefighting have been observed. Firefighters are exposed to harmful substances that include known carcinogens. This meta-analysis aimed to synthesise the available published evidence on prostate cancer risk in firefighters. Methods A comprehensive search of PubMed and Web of Science was conducted for all epidemiological studies on firefighting and prostate cancer published in English from 1980–2017. Studies that reported on risk estimates for incidence and/or mortality with corresponding ever/never employment were extracted from included studies. Meta risk estimates (mRE) were determined in a random effects model and between-study heterogeneity was evaluated based on I 2 values. Results Of the 101 studies retrieved, 25 firefighter studies were included in this analysis. Ever employment as a firefighter, based on results from all studies, was associated with a 15% increase in prostate cancer risk (95% CI 1.04–1.27, I 2 =71%). By study design, the mRE was 1.14 (95% CI 1.03–1.26, I 2 =67%) for 18 cohort studies and 1.22 (95% CI 0.90–1.67, I 2 =82%) for 5 case-control studies. Incidence studies had an mRE of 1.17 (95% CI 1.07–1.28, I 2 =74%) and mortality studies had an mRE of 1.12 (95% CI 0.92–1.36, I 2 =50%). For linkage and registry-based studies, an mRE of 1.19 (95% CI 1.05–1.33, I 2 =61%) was observed. Estimates showed moderate to substantial heterogeneity. Conclusions This analysis showed evidence of a small excess risk of prostate cancer in firefighters across study designs. Further evaluation of heterogeneity, potential biases, and quality assessment are currently underway.

Purpose To determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Methods Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case–control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Cases (n = 316) were identified through provincial cancer registries and hospital records. Controls (n = 1,506) were frequency-matched to cases by age (±2 years) within each province and were identified through provincial health records, telephone listings, or voter lists. The Cochran–Armitage test was used to check for trends within pesticide classes. Results Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88, 95 % CI 0.92–3.87) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16, 95 % CI 1.02–9.29). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47, 95 % CI 1.06–5.75), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. When analyses excluded proxy respondents, OR estimates strengthened in some circumstances. Conclusions This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens. These associations should be further evaluated, specifically in relation to age at diagnosis.

Multiple myeloma (MM) has been linked to certain agricultural exposures, including pesticides. This analysis aimed to investigate the association between lifetime use of multiple pesticides and MM risk using two exposure metrics: number of pesticides used and days per year of pesticide use. A frequency-matched, population-based case-control study was conducted among men in six Canadian provinces between 1991 and 1994. Data from 342 MM cases and 1,357 controls were analyzed using logistic regression to calculate odds ratios (OR) and 95% confidence intervals. Pesticides were grouped by type, chemical class and carcinogenic potential, using a composite carcinogenic probability score. Selected individual pesticides were also examined. Regression models were adjusted for age, province of residence, use of proxy respondents, smoking and selected medical history variables. The overall pattern of results was complex. Positive trends in risk were observed for fungicides (ptrend=0.04) and pesticides classified as probably carcinogenic or higher (ptrend=0.03). Excess risks of MM were observed among men who reported using at least one carbamate pesticide (OR=1.94, 1.16-3.25), one phenoxy herbicide (OR=1.56, 1.09-2.25) and ≥3 organochlorines (OR=2.21, 1.05-4.66). Significantly higher odds of MM were seen for exposure to carbaryl (OR=2.71, 1.47-5.00) and captan (OR=2.96, 1.40-6.24). Use of mecoprop for >2 days per year was also significantly associated with MM (OR=2.15, 1.03-4.48). Focusing on multiple pesticide exposures is important because this more accurately reflects how exposures occur in occupational settings. Significant associations observed for certain chemical classes and individual pesticides suggest that these may be MM risk factors.

Objectives Prostate cancer continues to be the most commonly diagnosed cancer in North American men. There are few established risk factors and there is limited evidence on occupational risk factors for prostate cancer. The purpose of this study was to investigate the relationship between employment in specific industries and occupations and prostate cancer risk. Methods Data were used from the National Enhanced Cancer Surveillance System case-control study that was conducted in eight Canadian provinces. Between 1994 and 1997, mailed questionnaires were used to collect information on potential risk factors for cancer including lifetime occupational history. This analysis included 1737 prostate cancer cases and 1803 controls aged 50 to 79 years. Lifetime occupational histories were used to characterise associations between specific jobs and prostate cancer. Odds ratios and 95% confidence intervals were generated using logistic regression. Results By industry, an elevated risk was observed in protective services work, which included firefighters and police officers (OR = 1.39, 95% CI=1.17–1.64) and the elevated risk was observed for those with ≥10 years duration of employment. An elevated risk was observed in legal work (OR = 3.51, 95% CI = 1.53–8.06) and a reduced risk was observed in tourism and recreation work (OR = 0.58, 95% CI = 0.40–0.83). By occupation, an elevated risk was observed in plumbing and gas workers (OR = 1.74, 95% CI = 1.06–2.84) and in farming and agriculture workers (OR = 1.35, 95% CI = 1.02–1.79). An elevated risk was also observed in other protective services occupations (excluding firefighters and police) (OR = 1.33, 95% CI = 1.09–1.62). An excess was also observed in firefighters (OR = 1.56, 95% CI = 0.90–2.69), based on small numbers. Conclusions Despite the relatively large size of this study, few associations were observed. Excess risks among protective service workers, particularly firefighters, and agricultural workers have been previously observed. Additional studies using improved exposure assessment methods, including occupation specific chemical and physical exposures, are needed.