Canadian Census Health Research Articles

Occupation and Risk of Bladder Cancer: A Population Level Comparison of Nordic Countries and Canada

Background/Aim: Associations with bladder cancer have been observed for more than 40 occupations. While some findings have been consistent, others have been inconsistent or limited. Outside of the Nordic countries, only few countries have directly linked information on cancer and census data. The aim of the study was to compare occupational variation of the risk of bladder cancer in the Nordic countries and Canada. Methods: In the Nordic occupational cancer study (NOCCA) 73,653 bladder cancer cases were observed during follow up of 141.6 million person years. In the Canadian Census Health and Environment Cohort (CanCHEC) 8,170 cases were observed during 36.7 million person years of follow up. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were estimated for 53 occupations in the NOCCA cohort and hazard ratios (HR) with 95% CIs were estimated for 42 occupations in the CanCHEC cohort. Results: Elevated risks of bladder cancer were observed among hairdressers, printers, sales workers, plumbers, painters, miners, and laundry workers. Teachers and agricultural workers had reduced risk of bladder cancer in both cohorts. Chimney sweeps, tobacco workers and waiters had about 1.5-fold risk in the Nordic countries; no risk estimates for these categories were given from the CanCHEC cohort. Conclusions: We observed different occupational patterns in risk of bladder cancer in Nordic countries and Canada. The only occupation with similarly increased risk was observed among sales workers. Differences in smoking across occupational groups may explain some, but not all, of this variation.

Associations between long-term PM2.5 and ozone exposure and mortality in the Canadian Census Health and Environment Cohort (CANCHEC), by spatial synoptic classification zone

Studies suggest that long-term chronic exposure to fine particulate matter air pollution can increase lung cancer mortality. We analyzed the association between long term PM2.5 and ozone exposure and mortality due to lung cancer, ischemic heart disease, and chronic obstructive pulmonary disease, accounting for geographic location, socioeconomic status, and residential mobility. Subjects in the 1991 Canadian Census Health and Environment Cohort (CanCHEC) were followed for 20years, and assigned to regions across Canada based on spatial synoptic classification weather types. Hazard ratios (HR) for mortality, were related to PM2.5 and ozone using Cox proportional hazards survival models, adjusting for socioeconomic characteristics and individual confounders. An increase of 10μg/m3 in long term PM2.5 exposure resulted in an HR for lung cancer mortality of 1.26 (95% CI 1.04, 1.53); the inclusion in the model of SSC zone as a stratum increased the risk estimate to HR 1.29 (95% CI 1.06, 1.57). After adjusting for ozone, HRs increased to 1.49 (95% CI 1.23, 1.88), and HR 1.54 (95% CI 1.27, 1.87), with and without zone as a model stratum. HRs for ischemic heart disease fell from 1.25 (95% CI 1.21, 1.29) for exposure to PM2.5, to 1.13 (95% CI 1.08, 1.19) when PM2.5 was adjusted for ozone. For COPD, the 95% confidence limits included 1.0 when climate zone was included in the model. HRs for all causes of death showed spatial differences when compared to zone 3, the most populated climate zone. Exposure to PM2.5 was related to an increased risk of mortality from lung cancer, and both ozone and PM2.5 exposure were related to risk of mortality from ischemic heart disease, and the risk varied spatially by climate zone.

Impact of Oxidant Gases on the Relationship between Outdoor Fine Particulate Air Pollution and Nonaccidental, Cardiovascular, and Respiratory Mortality

Outdoor fine particulate air pollution (PM2.5) is known to increase mortality risk and is recognized as an important contributor to global disease burden. However, less is known about how oxidant gases may modify the chronic health effects of PM2.5. In this study, we examined how the oxidant capacity of O3 and NO2 (using a redox-weighted average, Ox) may modify the relationship between PM2.5 and mortality in the 2001 Canadian Census Health and Environment Cohort. In total, 2,448,500 people were followed over a 10.6-year period. Each 3.86 µg/m3 increase in PM2.5 was associated with nonaccidental (Hazard Ratio (HR) = 1.095, 95% CI: 1.077, 1.112), cardiovascular (HR = 1.088, 95% CI: 1.059, 1.118), and respiratory mortality (HR = 1.110, 95% CI: 1.051, 1.171) in the highest tertile of Ox whereas weaker/null associations were observed in the middle and lower tertiles. Analysis of joint non-linear concentration-response relationships for PM2.5 and Ox suggested threshold concentrations between approximately 23 and 25 ppb with Ox concentrations above these values strengthening PM2.5-mortality associations. Overall, our findings suggest that oxidant gases enhance the chronic health risks of PM2.5. In some areas, reductions in Ox concentrations may have the added benefit of reducing the public health impacts of PM2.5 even if mass concentrations remain unchanged.

Urban greenness and mortality in Canada's largest cities: a national cohort study

Findings from published studies suggest that exposure to and interactions with green spaces are associated with improved psychological wellbeing and have cognitive, physiological, and social benefits, but few studies have examined their potential effect on the risk of mortality. We therefore undertook a national study in Canada to examine associations between urban greenness and cause-specific mortality. We used data from a large cohort study (the 2001 Canadian Census Health and Environment Cohort [2001 CanCHEC]), which consisted of approximately 1·3 million adult (aged ≥19 years), non-immigrant, urban Canadians in 30 cities who responded to the mandatory 2001 Statistics Canada long-form census. The cohort has been linked by Statistics Canada to the Canadian mortality database and to annual income tax filings through 2011. We measured greenness with images from the moderate-resolution imaging spectroradiometer from NASA's Aqua satellite. We assigned estimates of exposure to greenness derived from remotely sensed Normalized Difference Vegetation Index (NDVI) within both 250 m and 500 m of participants' residences for each year during 11 years of follow-up (between 2001 and 2011). We used Cox proportional hazards models to estimate associations between residential greenness (as a continuous variable) and mortality. We estimated hazard ratios (HRs) and corresponding 95% CIs per IQR (0·15) increase in NDVI adjusted for personal (eg, education and income) and contextual covariates, including exposures to fine particulate matter, ozone, and nitrogen dioxide. We also considered effect modification by selected personal covariates (age, sex, household income adequacy quintiles, highest level of education, and marital status). Our cohort consisted of approximately 1 265 000 individuals at baseline who contributed 11 523 770 person-years. We showed significant decreased risks of mortality in the range of 8-12% from all causes of death examined with increased greenness around participants' residence. In the fully adjusted analyses, the risk was significantly decreased for all causes of death (non-accidental HR 0·915, 95% CI 0·905-0·924; cardiovascular plus diabetes 0·911, 0·895-0·928; cardiovascular 0·911, 0·894-0·928; ischaemic heart disease 0·904, 0·882-0·927; cerebrovascular 0·942, 0·902-0·983; and respiratory 0·899, 0·869-0·930). Greenness associations were more protective among men than women (HR 0·880, 95% CI 0·868-0·893 vs 0·955, 0·941-0·969), and among individuals with higher incomes (highest quintile 0·812, 0·791-0·834 vs lowest quintile 0·991, 0·972-1·011) and more education (degree or more 0·816, 0·791-0·842 vs did not complete high school 0·964, 0·950-0·978). Increased amounts of residential greenness were associated with reduced risks of dying from several common causes of death among urban Canadians. We identified evidence of inequalities, both in terms of exposures to greenness and mortality risks, by personal socioeconomic status among individuals living in generally similar environments, and with reasonably similar access to health care and other social services. The findings support the development of policies related to creating greener and healthier cities. None.

Associations between fine particulate matter and mortality in the 2001 Canadian Census Health and Environment Cohort

BackgroundLarge cohort studies have been used to characterise the association between long-term exposure to fine particulate matter (PM2.5) air pollution with non-accidental, and cause-specific mortality. However, there has been no consensus as to the shape of the association between concentration and response. MethodsTo examine the shape of this association, we developed a new cohort based on respondents to the 2001 Canadian census long-form. We applied new annual PM2.5 concentration estimates based on remote sensing and ground measurements for Canada at a 1km spatial scale from 1998 to 2011. We followed 2.4 million respondents who were non-immigrants aged 25–90 years and did not reside in an institution over a 10 year period for mortality. Exposures were assigned as a 3-year mean prior to the follow-up year. Income tax files were used to account for residential mobility among respondents using postal codes, with probabilistic imputation used for missing postal codes in the tax data. We used Cox survival models to determine hazard ratios (HRs) for cause-specific mortality. We also estimated Shape Constrained Health Impact Functions (a concentration-response function) for selected causes of death. ResultsIn models stratified by age, sex, airshed, and population centre size, and adjusted for individual and neighbourhood socioeconomic variables, HR estimates for non-accidental mortality were HR = 1.18 (95% CI: 1.15–1.21) per 10μg/m3 increase in concentration. We observed higher HRs for cardiovascular disease (HR=1.25; 95% CI: 1.19–1.31), cardio-metabolic disease (HR = 1.27; 95% CI: 1.21–1.33), ischemic heart disease (HR = 1.36; 95% CI: 1.28–1.44) and chronic obstructive pulmonary disease (COPD) mortality (HR = 1.24; 95% CI: 1.11–1.39) compared to HR for all non-accidental causes of death. For non-accidental, cardio-metabolic, ischemic heart disease, respiratory and COPD mortality, the shape of the concentration-response curve was supra-linear, with larger differences in relative risk for lower concentrations. For both pneumonia and lung cancer, there was some suggestion that the curves were sub-linear. ConclusionsAssociations between ambient concentrations of fine particulate matter and several causes of death were non-linear for each cause of death examined.

Occupational variation in incidence of bladder cancer: a comparison of population-representative cohorts from Nordic countries and Canada

ObjectivesThe objective of this study was to compare occupational variation of the risk of bladder cancer in the Nordic countries and Canada.MethodsIn the Nordic Occupational Cancer study (NOCCA), 73 653...

Sedentary work and the risks of colon and rectal cancer by anatomical sub-site in the Canadian census health and environment cohort (CanCHEC)

BackgroundSedentary behaviour is a potential risk factor for colorectal cancer. We examined the association between sedentary work, based on body position, and colorectal cancer risk in Canadians. MethodsA working body position category (a. sitting; b. standing and walking; c. sitting, standing, and walking; d. other) was assigned to occupations reported by 1991 Canadian Census respondents based on national occupational counselling guidelines. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for cancers of the colon (overall, proximal, and distal) and rectum in men and women newly diagnosed from 1992 to 2010. ResultsCompared to “sitting” jobs, men in occupations with “other” (non-sitting, −standing, or −walking) body positions had a weakly significant reduced colon cancer risk (HR=0.93, 95% CI: 0.89, 0.98) primarily attributed to protection at the distal site (HR=0.90, 95% CI: 0.84, 0.97). Men in “standing and walking” and “sitting, standing, and walking” jobs did not have significantly reduced colon cancer risks. No effects were observed for rectal cancer in men or colon and rectal cancer in women. ConclusionThe two significant findings of this analysis should be followed-up in further investigations with additional information on potential confounders. Null findings for rectal cancer were consistent with other studies.

Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC)

BackgroundAgricultural workers may be exposed to potential carcinogens including pesticides, sensitizing agents and solar radiation. Previous studies indicate increased risks of hematopoietic cancers and decreased risks at other sites, possibly due to differences in lifestyle or risk behaviours. We present findings from CanCHEC (Canadian Census Health and Environment Cohort), the largest national population-based cohort of agricultural workers.MethodsStatistics Canada created the cohort using deterministic and probabilistic linkage of the 1991 Canadian Long Form Census to National Cancer Registry records for 1992–2010. Self-reported occupations were coded using the Standard Occupational Classification (1991) system. Analyses were restricted to employed persons aged 25–74 years at baseline (N = 2,051,315), with follow-up until December 31, 2010. Hazard ratios (HR) and 95% confidence intervals (CI) were modeled using Cox proportional hazards for all workers in agricultural occupations (n = 70,570; 70.8% male), stratified by sex, and adjusted for age at cohort entry, province of residence, and highest level of education.ResultsA total of 9515 incident cancer cases (7295 in males) occurred in agricultural workers. Among men, increased risks were observed for non-Hodgkin lymphoma (HR = 1.10, 95% CI = 1.00–1.21), prostate (HR = 1.11, 95% CI = 1.06–1.16), melanoma (HR = 1.15, 95% CI = 1.02–1.31), and lip cancer (HR = 2.14, 95% CI = 1.70–2.70). Decreased risks in males were observed for lung, larynx, and liver cancers. Among female agricultural workers there was an increased risk of pancreatic cancer (HR = 1.36, 95% CI = 1.07–1.72). Increased risks of melanoma (HR = 1.79, 95% CI = 1.17–2.73), leukemia (HR = 2.01, 95% CI = 1.24–3.25) and multiple myeloma (HR = 2.25, 95% CI = 1.16–4.37) were observed in a subset of female crop farmers.ConclusionsExposure to pesticides may have contributed to increased risks of hematopoietic cancers, while increased risks of lip cancer and melanoma may be attributed to sun exposure. The array of decreased risks suggests reduced smoking and alcohol consumption in this occupational group compared to the general population.

Cancer Risks among Welders and Occasional Welders in a National Population-Based Cohort Study: Canadian Census Health and Environmental Cohort.

BackgroundWelders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort.MethodsAmong 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992–2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders.ResultsAmong welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03–1.31], mesothelioma (HR: 1.78, 95% CI: 1.01–3.18), bladder cancer (HR: 1.40, 95% CI: 1.15–1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01–1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased.ConclusionExcess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.

Geographical Variation and Factors Associated with Non-Small Cell Lung Cancer in Manitoba.

Background Screening decreases non-small cell lung cancer (NSCLC) deaths and is recommended by the Canadian Task Force on Preventive Health Care. We investigated risk factor prevalence and NSCLC incidence at a small region level to inform resource allocation for lung cancer screening. Methods NSCLC diagnoses were obtained from the Canadian Cancer Registry, then geocoded to 283 small geographic areas (SGAs) in Manitoba. Sociodemographic characteristics of SGAs were obtained from the 2006 Canadian Census and Canadian Community Health Survey. Geographical variation was modelled using a Bayesian spatial Poisson model. Results NSCLC incidence in SGAs ranged from 1 to 343 cases per 100,000 population per year. The highest incidence rates were in the Southeastern, Southwestern, and Central regions of Manitoba, while most of Northern Manitoba had lower rates. Poisson regression suggested areas with higher proportions of Aboriginal people and higher average income, and immigrants had lower NSCLC incidence whereas areas with higher proportions of smokers had higher incidence. Conclusion On an SGA level, smoking rates remain the most significant factor driving NSCLC incidence. Socioeconomic status and proportions of immigrants or Aboriginal peoples independently impact NSCLC rates. We have identified SGAs in Manitoba to target in policy and infrastructure planning for lung cancer screening.

Health benefits of reducing NOx emissions in the presence of epidemiological and atmospheric nonlinearities

Recent epidemiological evidence suggests that the logarithm of concentration is a better predictor of mortality risk from long-term exposure to ambient PM2.5 and NO2 than concentration itself. A log-concentration-response function (CRF) predicts a heightened excess risk per unit concentration at low levels of exposure that further increases as the air becomes less polluted. Using an adjoint air quality model, we estimate the public health benefits of reducing NOx emissions, on a per-ton and source-by-source basis. Our estimates of benefits-per-ton assume linear in concentration and log-concentration CRFs for NO2 and a CRF that is linear in concentration for O3. We apply risk coefficients estimated using the Canadian Census Health and Environment Cohort. We find that a log-concentration CRF for NO2 leads almost consistently to larger benefits-per-ton than a linear in concentration CRF (e.g., $500 000 ton−1 compared to $270 000 ton−1 for Ottawa). We observe that concentrations gradually decline due to widespread, progressive emissions abatement, entailing increasing health benefits as a result of (1) a log-concentration CRF for NO2 and (2) the nonlinear response of O3 to NOx emissions. Our results indicate that NOx abatement has the potential to incur substantial and increasing health benefits, by up to five times with 85% emission reductions, for Canada into the future.

Ozone exposure and cardiovascular-related mortality in the Canadian Census Health and Environment Cohort (CANCHEC) by spatial synoptic classification zone

Our objective is to analyse the association between long term ozone exposure and cardiovascular related mortality while accounting for climate, location, and socioeconomic factors. We assigned subjects with 16 years of follow-up in the Canadian Census Health and Environment Cohort (CanCHEC) to one of seven regions based on spatial synoptic classification (SSC) weather types and examined the interaction of exposure to both fine particulate matter (PM2.5) and ground level ozone and cause of death using survival analysis, while adjusting for socioeconomic characteristics and individual confounders. Correlations between ozone and PM2.5 varied across SSC zones from −0.02 to 0.7. Comparing zones using the most populated SSC zone as a reference, a 10 ppb increase in ozone exposure was associated with increases in hazard ratios (HRs) that ranged from 1.007 (95% CI 0.99, 1.015) to 1.03 (95% CI 1.02, 1.041) for cardiovascular disease, 1.013 (95% CI 0.996, 1.03) to 1.058 (95% CI 1.034, 1.082) for cerebrovascular disease, and 1.02 (95% CI 1.006, 1.034) for ischemic heart disease. HRs remained significant after adjustment for PM2.5. Long term exposure to ozone is related to an increased risk of mortality from cardiovascular and cerebrovascular diseases; the risk varies by location across Canada and is not attenuated by adjustment for PM2.5. This research shows that the SSC can be used to define geographic regions and it demonstrates the importance of accounting for that spatial variability when studying the long term health effects of air pollution.

A class of non-linear exposure-response models suitable for health impact assessment applicable to large cohort studies of ambient air pollution.

The effectiveness of regulatory actions designed to improve air quality is often assessed by predicting changes in public health resulting from their implementation. Risk of premature mortality from long-term exposure to ambient air pollution is the single most important contributor to such assessments and is estimated from observational studies generally assuming a log-linear, no-threshold association between ambient concentrations and death. There has been only limited assessment of this assumption in part because of a lack of methods to estimate the shape of the exposure-response function in very large study populations. In this paper, we propose a new class of variable coefficient risk functions capable of capturing a variety of potentially non-linear associations which are suitable for health impact assessment. We construct the class by defining transformations of concentration as the product of either a linear or log-linear function of concentration multiplied by a logistic weighting function. These risk functions can be estimated using hazard regression survival models with currently available computer software and can accommodate large population-based cohorts which are increasingly being used for this purpose. We illustrate our modeling approach with two large cohort studies of long-term concentrations of ambient air pollution and mortality: the American Cancer Society Cancer Prevention Study II (CPS II) cohort and the Canadian Census Health and Environment Cohort (CanCHEC). We then estimate the number of deaths attributable to changes in fine particulate matter concentrations over the 2000 to 2010 time period in both Canada and the USA using both linear and non-linear hazard function models.Electronic supplementary materialThe online version of this article (doi:10.1007/s11869-016-0398-z) contains supplementary material, which is available to authorized users.

Oxidative burden of fine particulate air pollution and risk of cause-specific mortality in the Canadian Census Health and Environment Cohort (CanCHEC)

BackroundFine particulate air pollution (PM2.5) is known to contribute to cardiorespiratory mortality but it is not clear how PM2.5 oxidative burden (i.e. the ability of PM2.5 to cause oxidative stress) may influence long-term mortality risk. MethodsWe examined the relationship between PM2.5 oxidative burden and cause-specific mortality in Ontario, Canada. Integrated PM2.5 samples were collected from 30 provincial monitoring sites between 2012 and 2013. The oxidative potential (% depletion/µg) of regional PM2.5 was measured as the ability of filter extracts to deplete antioxidants (glutathione and ascorbate) in a synthetic respiratory tract lining fluid. PM2.5oxidative burden was calculated as the product of PM2.5 mass concentrations and regional estimates of oxidative potential. In total, this study included 193,300 people who completed the Canadian long-form census in 1991 and who lived within 5km of a site where oxidative potential was measured. Deaths occurring between 1991 and 2009 were identified through record linkages and Cox proportional hazard models were used to estimate hazard ratios (and 95% confidence intervals) for interquartile changes in exposure adjusting for individual-level covariates and indirect-adjustment for smoking and obesity. ResultsGlutathione-related oxidative burden was associated with cause-specific mortality. For lung cancer specifically, this metric was associated with a 12% (95% CI: 5.0–19) increased risk of mortality whereas a 5.0% (95% CI: 0.1, 10) increase was observed for PM2.5. Indirect adjustment for smoking and obesity decreased the lung cancer hazard ratio for glutathione-related oxidative burden but it remained significantly elevated (HR=1.07, 95% CI: 1.005, 1.146). Ascorbate-related oxidative burden was not associated with mortality. ConclusionsOur findings suggest that glutathione-related oxidative burden may be more strongly associated with lung cancer mortality than PM2.5 mass concentrations.

Ambient PM2.5, O₃, and NO₂ Exposures and Associations with Mortality over 16 Years of Follow-Up in the Canadian Census Health and Environment Cohort (CanCHEC).

BackgroundFew studies examining the associations between long-term exposure to ambient air pollution and mortality have considered multiple pollutants when assessing changes in exposure due to residential mobility during follow-up.ObjectiveWe investigated associations between cause-specific mortality and ambient concentrations of fine particulate matter (≤ 2.5 μm; PM2.5), ozone (O3), and nitrogen dioxide (NO2) in a national cohort of about 2.5 million Canadians.MethodsWe assigned estimates of annual concentrations of these pollutants to the residential postal codes of subjects for each year during 16 years of follow-up. Historical tax data allowed us to track subjects’ residential postal code annually. We estimated hazard ratios (HRs) for each pollutant separately and adjusted for the other pollutants. We also estimated the product of the three HRs as a measure of the cumulative association with mortality for several causes of death for an increment of the mean minus the 5th percentile of each pollutant: 5.0 μg/m3 for PM2.5, 9.5 ppb for O3, and 8.1 ppb for NO2.ResultsPM2.5, O3, and NO2 were associated with nonaccidental and cause-specific mortality in single-pollutant models. Exposure to PM2.5 alone was not sufficient to fully characterize the toxicity of the atmospheric mix or to fully explain the risk of mortality associated with exposure to ambient pollution. Assuming additive associations, the estimated HR for nonaccidental mortality corresponding to a change in exposure from the mean to the 5th percentile for all three pollutants together was 1.075 (95% CI: 1.067, 1.084). Accounting for residential mobility had only a limited impact on the association between mortality and PM2.5 and O3, but increased associations with NO2.ConclusionsIn this large, national-level cohort, we found positive associations between several common causes of death and exposure to PM2.5, O3, and NO2.CitationCrouse DL, Peters PA, Hystad P, Brook JR, van Donkelaar A, Martin RV, Villeneuve PJ, Jerrett M, Goldberg MS, Pope CA III, Brauer M, Brook RD, Robichaud A, Menard R, Burnett RT. 2015. Ambient PM2.5, O3, and NO2 exposures and associations with mortality over 16 years of follow-up in the Canadian Census Health and Environment Cohort (CanCHEC). Environ Health Perspect 123:1180–1186; http://dx.doi.org/10.1289/ehp.1409276

Within- and between-city contrasts in nitrogen dioxide and mortality in 10 Canadian cities; a subset of the Canadian Census Health and Environment Cohort (CanCHEC).

The independent and joint effects of within- and between-city contrasts in air pollution on mortality have been investigated rarely. To examine the differential effects of between- versus within-city contrasts in pollution exposure, we used both ambient measurements and land use regression models to assess associations with mortality and exposure to nitrogen dioxide (NO2) among ~735,600 adults in 10 of the largest Canadian cities. We estimated exposure contrasts partitioned into within- and between-city contrasts, and the sum of these as overall exposures, for every year from 1984 to 2006. Residential histories allowed us to follow subjects annually during the study period. We calculated hazard ratios (HRs) adjusted for many personal and contextual variables. In fully-adjusted, random-effects models, we found positive associations between overall NO2 exposures and mortality from non-accidental causes (HR per 5 p.p.b.: 1.05; 95% confidence interval (CI): 1.03–1.07), cardiovascular disease (HR per 5 p.p.b.: 1.04; 95% CI: 1.01–1.06), ischaemic heart disease (HR per 5 p.p.b.: 1.05; 95% CI: 1.02–1.08) and respiratory disease (HR per 5 p.p.b.: 1.04; 95% CI: 0.99–1.08), but not from cerebrovascular disease (HR per 5 p.p.b.: 1.01; 95% CI: 0.96–1.06). We found that most of these associations were determined by within-city contrasts, as opposed to by between-city contrasts in NO2. Our results suggest that variation in NO2 concentrations within a city may represent a more toxic mixture of pollution than variation between cities.