Long-term exposure to wildfires and cancer incidence in Canada: a population-based observational cohort study.

BACKGROUND: Wildfires emit many carcinogenic pollutants that contaminate air, water, terrestrial, and indoor environments. However, little is known about the relationship between exposure to wildfires and cancer risk. We aimed to assess the associations between residential exposure to wildfires and the incidence of several cancer outcomes (lung cancer, brain cancer, non-Hodgkin lymphoma, multiple myeloma, and leukaemia) in Canada. METHODS: We did a population-based observational cohort study of participants in the 1996 Canadian Census Health and Environment Cohort. The 1996 Canadian Census Health and Environment Cohort is a nationally representative sample of Canadian adults, followed up for cancer incidence and mortality from 1996 to 2015. For this analysis, we excluded participants who lived in major Canadian cities (with a population size greater than 1·5 million people), recent immigrants, and individuals younger than 25 years or 90 years of age or older at baseline. Exposures to wildfires were assigned on the basis of area burned within a 20 km or 50 km radius of residential locations and updated for annual residential mobility. Multivariable Cox proportional hazards models were used to estimate associations between exposure to wildfires and specific cancers associated with carcinogenic compounds released by wildfires, including lung and brain cancer, non-Hodgkin lymphoma, multiple myeloma, and leukaemia, adjusted for many personal and neighbourhood-level covariates. FINDINGS: Our analyses included more than 2 million people followed up for a median of 20 years, for a total of 34 million person-years. Wildfire exposure was associated with slightly increased incidence of lung cancer and brain tumours. For example, cohort members exposed to a wildfire within 50 km of residential locations in the past 10 years had a 4·9% relatively higher incidence (adjusted hazard ratio [HR] 1·049, 95% CI 1·028-1·071) of lung cancer than unexposed populations, and a 10% relatively higher incidence (adjusted HR 1·100, 1·026-1·179) of brain tumours. Similar associations were observed for the 20 km buffer size. Wildfires were not associated with haematological cancers in this study, and concentration-response trends were not readily apparent when area burned was modelled as a continuous variable. INTERPRETATION: Long-term exposure to wildfires might increase the risk of lung cancer and brain tumours. Further work is needed to develop long-term estimates of wildfire exposures that capture the complex mixture of environmental pollutants released during these events. FUNDING: Canadian Institute for Health Research and Fonds de recherche du Quebec.

Changes in exposure to ambient fine particulate matter after relocating and long term survival in Canada: quasi-experimental study.

OBJECTIVE: To investigate the association between changes in long term residential exposure to ambient fine particulate matter (PM2.5) and premature mortality in Canada. DESIGN: Population based quasi-experimental study. SETTING: Canada. PARTICIPANTS: 663 100 respondents to the 1996, 2001, and 2006 Canadian censuses aged 25-89 years who had consistently lived in areas with either high or low PM2.5 levels over five years preceding census day and moved during the ensuing five years. INTERVENTIONS: Changes in long term exposure to PM2.5 arising from residential mobility. MAIN OUTCOME MEASURES: The primary outcome was deaths from natural causes. Secondary outcomes were deaths from any cardiometabolic cause, any respiratory cause, and any cancer cause. All outcomes were obtained from the national vital statistics database. RESULTS: Using a propensity score matching technique with numerous personal, socioeconomic, health, and environment related covariates, each participant who moved to a different PM2.5 area was matched with up to three participants who moved within the same PM2.5 area. In the matched groups that moved from high to intermediate or low PM2.5 areas, residential mobility was associated with a decline in annual PM2.5 exposure from 10.6 µg/m3 to 7.4 and 5.0 µg/m3, respectively. Conversely, in the matched groups that moved from low to intermediate or high PM2.5 areas, annual PM2.5 increased from 4.6 µg/m3 to 6.7 and 9.2 µg/m3. Five years after moving, individuals who experienced a reduction in exposure to PM2.5 from high to intermediate levels showed a 6.8% (95% confidence interval 1.7% to 11.7%) reduction in mortality (2510 deaths in 56 025 v 4925 deaths in 101 960). A greater decline in mortality occurred among those exposed to a larger reduction in PM2.5. Increased mortality was found with exposure to PM2.5 from low to high levels, and to a lesser degree from low to intermediate levels. Furthermore, the decreases in PM2.5 exposure were most strongly associated with reductions in cardiometabolic deaths, whereas the increases in PM2.5 exposure were mostly related to respiratory deaths. No strong evidence was found for the changes in PM2.5 exposure with cancer related deaths. CONCLUSIONS: In Canada, decreases in PM2.5 were associated with lower mortality, whereas increases in PM2.5 were associated with higher mortality. These results were observed at PM2.5 levels considerably lower than many other countries, providing support for continuously improving air quality.

Disease assimilation: The mortality impacts of fine particulate matter on immigrants to Canada.

BACKGROUND: Immigrants make up 20% of the Canadian population; however, little is known about the mortality impacts of fine particulate matter (PM2.5) air pollution on immigrants compared with non-immigrants, or about how impacts may change with duration in Canada. DATA AND METHODS: This study used the 2001 Canadian Census Health and Environment Cohort, a longitudinal cohort of 3.5 million individuals, of which 764,000 were classified as immigrants (foreign-born). Postal codes from annual income tax files were used to account for mobility among respondents and to assign annual PM2.5 concentrations from 1998 to 2016. Exposures were estimated as a three-year moving average prior to the follow-up year. Cox survival models were used to determine hazard ratios (HRs) for cause-specific mortality, comparing the Canadian and foreign-born populations, with further stratification by year of immigration grouped into 10-year cohorts. RESULTS: Differences in urban-rural settlement patterns resulted in greater exposure to PM2.5 for immigrants compared with non-immigrants (mean = 9.3 vs. 7.5 µg/m3), with higher exposures among more recent immigrants. In fully adjusted models, immigrants had higher HRs per 10 µg/m3 increase in PM2.5 concentration compared with Canadian-born individuals for cardiovascular mortality (HR [95% confidence interval] = 1.22 [1.12 to 1.34] vs. 1.12 [1.07 to 1.18]) and cerebrovascular mortality (HR = 1.25 [1.03 to 1.52] vs. 1.03 [0.93 to 1.15]), respectively. However, tests for differences between the two groups were not significant when Cochran's Q test was used. No significant associations were found for respiratory outcomes, except for lung cancer in non-immigrants (HR = 1.10 [1.02 to 1.18]). When stratified by year of immigration, differences in HRs across varied by cause of death. DISCUSSION: In Canada, PM2.5 is an equal-opportunity risk factor, with immigrants experiencing similar if not higher mortality risks compared with non-immigrants for cardiovascular-related causes of death. Some notable differences also existed with cerebrovascular and lung cancer deaths. Continued reductions in air pollution, particularly in urban areas, will improve the health of the Canadian population as a whole.

Evaluating the Sensitivity of PM2.5-Mortality Associations to the Spatial and Temporal Scale of Exposure Assessment.

BACKGROUND: The temporal and spatial scales of exposure assessment may influence observed associations between fine particulate air pollution (PM2.5) and mortality, but few studies have systematically examined this question. METHODS: We followed 2.4 million adults in the 2001 Canadian Census Health and Environment Cohort for nonaccidental and cause-specific mortality between 2001 and 2011. We assigned PM2.5 exposures to residential locations using satellite-based estimates and compared three different temporal moving averages (1, 3, and 8 years) and three spatial scales (1, 5, and 10 km) of exposure assignment. In addition, we examined different spatial scales based on age, employment status, and urban/rural location, and adjustment for O3, NO2, or their combined oxidant capacity (Ox). RESULTS: In general, longer moving averages resulted in stronger associations between PM2.5 and mortality. For nonaccidental mortality, we observed a hazard ratio of 1.11 (95% CI = 1.08, 1.13) for the 1-year moving average compared with 1.23 (95% CI = 1.20, 1.27) for the 8-year moving average. Respiratory and lung cancer mortality were most sensitive to the spatial scale of exposure assessment with stronger associations observed at smaller spatial scales. Adjustment for oxidant gases attenuated associations between PM2.5 and cardiovascular mortality and strengthened associations with lung cancer. Despite these variations, PM2.5 was associated with increased mortality in nearly all of the models examined. CONCLUSIONS: These findings support a relationship between outdoor PM2.5 and mortality at low concentrations and highlight the importance of longer-exposure windows, more spatially resolved exposure metrics, and adjustment for oxidant gases in characterizing this relationship.

Cohort profile: The Canadian Census Health and Environment Cohorts (CanCHECs).

The Canadian Census Health and Environment Cohorts (CanCHECs) are population-based linked datasets of the household population at the time of census collection. The CanCHECs combine data from respondents to the long-form census or the National Household Survey between 1991 and 2011 with administrative health data (e.g., mortality, cancer incidence, hospitalizations, emergency ambulatory care) and annual mailing address postal codes. The CanCHEC datasets are rich national data resources that can be used to measure and examine health inequalities across socioeconomic and ethnocultural dimensions for different periods and locations. These datasets can also be used to examine the effects of exposure to environmental factors on human health. Because of their large size, the CanCHECs are an excellent resource for examining rare health outcomes and small population groups. They are ideally suited for environmental health research because of their geographic coverage across all regions of Canada, their long follow-up periods and their linkage to annual postal code history.

Low concentrations of fine particle air pollution and mortality in the Canadian Community Health Survey cohort.

BACKGROUND: Approximately 2.9 million deaths are attributed to ambient fine particle air pollution around the world each year (PM2.5). In general, cohort studies of mortality and outdoor PM2.5 concentrations have limited information on individuals exposed to low levels of PM2.5 as well as covariates such as smoking behaviours, alcohol consumption, and diet which may confound relationships with mortality. This study provides an updated and extended analysis of the Canadian Community Health Survey-Mortality cohort: a population-based cohort with detailed PM2.5 exposure data and information on a number of important individual-level behavioural risk factors. We also used this rich dataset to provide insight into the shape of the concentration-response curve for mortality at low levels of PM2.5. METHODS: Respondents to the Canadian Community Health Survey from 2000 to 2012 were linked by postal code history from 1981 to 2016 to high resolution PM2.5 exposure estimates, and mortality incidence to 2016. Cox proportional hazard models were used to estimate the relationship between non-accidental mortality and ambient PM2.5 concentrations (measured as a three-year average with a one-year lag) adjusted for socio-economic, behavioural, and time-varying contextual covariates. RESULTS: In total, 50,700 deaths from non-accidental causes occurred in the cohort over the follow-up period. Annual average ambient PM2.5 concentrations were low (i.e. 5.9 µg/m3, s.d. 2.0) and each 10 µg/m3 increase in exposure was associated with an increase in non-accidental mortality (HR = 1.11; 95% CI 1.04-1.18). Adjustment for behavioural covariates did not materially change this relationship. We estimated a supra-linear concentration-response curve extending to concentrations below 2 µg/m3 using a shape constrained health impact function. Mortality risks associated with exposure to PM2.5 were increased for males, those under age 65, and non-immigrants. Hazard ratios for PM2.5 and mortality were attenuated when gaseous pollutants were included in models. CONCLUSIONS: Outdoor PM2.5 concentrations were associated with non-accidental mortality and adjusting for individual-level behavioural covariates did not materially change this relationship. The concentration-response curve was supra-linear with increased mortality risks extending to low outdoor PM2.5 concentrations.

Evaluation of a method to indirectly adjust for unmeasured covariates in the association between fine particulate matter and mortality.

BACKGROUND: Indirect adjustment via partitioned regression is a promising technique to control for unmeasured confounding in large epidemiological studies. The method uses a representative ancillary dataset to estimate the association between variables missing in a primary dataset with the complete set of variables of the ancillary dataset to produce an adjusted risk estimate for the variable in question. The objective of this paper is threefold: 1) evaluate the method for non-linear survival models, 2) formalize an empirical process to evaluate the suitability of the required ancillary matching dataset, and 3) test modifications to the method to incorporate time-varying exposure data, and proportional weighting of datasets. METHODS: We used the association between fine particle air pollution (PM2.5) with mortality in the 2001 Canadian Census Health and Environment Cohort (CanCHEC, N = 2.4 million, 10-years follow-up) as our primary dataset, and the 2001 cycle of the Canadian Community Health Survey (CCHS, N = 80,630) as the ancillary matching dataset that contained confounding risk factor information not available in CanCHEC (e.g., smoking). The main evaluation process used a gold-standard approach wherein two variables (education and income) available in both datasets were excluded, indirectly adjusted for, and compared to true models with education and income included to assess the amount of bias correction. An internal validation for objective 1 used only CanCHEC data, whereas an external validation for objective 2 replaced CanCHEC with the CCHS. The two proposed modifications were applied as part of the validation tests, as well as in a final indirect adjustment of four missing risk factor variables (smoking, alcohol use, diet, and exercise) in which adjustment direction and magnitude was compared to models using an equivalent longitudinal cohort with direct adjustment for the same variables. RESULTS: At baseline (2001) both cohorts had very similar PM2.5 distributions across population characteristics, although levels for CCHS participants were consistently 1.8-2.0 µg/m3 lower. Applying sample-weighting largely corrected for this discrepancy. The internal validation tests showed minimal downward bias in PM2.5 mortality hazard ratios of 0.4-0.6% using a static exposure, and 1.7-3% when a time-varying exposure was used. The external validation of the CCHS as the ancillary dataset showed slight upward bias of -0.7 to -1.1% and downward bias of 1.3-2.3% using the static and time-varying approaches respectively. CONCLUSIONS: The CCHS was found to be fairly well representative of CanCHEC and its use in Canada for indirect adjustment is warranted. Indirect adjustment methods can be used with survival models to correct hazard ratio point estimates and standard errors in models missing key covariates when a representative matching dataset is available. The results of this formal evaluation should encourage other cohorts to assess the suitability of ancillary datasets for the application of the indirect adjustment methodology to address potential residual confounding.

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

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.

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

BACKGROUND: Large 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. METHODS: To 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. RESULTS: In 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. CONCLUSIONS: Associations between ambient concentrations of fine particulate matter and several causes of death were non-linear for each cause of death examined.

The risk of melanoma associated with ambient summer ultraviolet radiation.

BACKGROUND: Depletion of the ozone layer has meant that ambient ultraviolet radiation (UVR) has increased in recent decades. At the same time, the incidence of skin cancers, including melanoma, has risen. The relatively few large-scale studies that linked ambient UVR to melanoma found a trend toward rising incidence closer to the equator, where UVR estimates are highest. Similar research has not been conducted in Canada, where ambient UVR is generally lower than in countries further south. DATA AND METHODS: Modelled UVR data for the months of June through August during the 1980-to-1990 period were spatially linked in Geographic Information Systems to 2.4 million white members of the 1991 Canadian Census Health and Environment Cohort and tracked for melanoma diagnosis over an 18-year period (1992 to 2009). Standard Cox proportional hazards models were used to estimate melanoma risk associated with increases of ambient summer UVR, assigned by residence at baseline. Models were adjusted for age, sex and socioeconomic (SES) characteristics. Separate analyses by body site of melanoma were conducted. Effect modification of the association between ambient UVR and melanoma by sex, age, outdoor occupation and selected SES characteristics was evaluated. RESULTS: Differences of one standard deviation (446 J/m², or 7% of the mean) in average ambient summer UVR were associated with an increased hazard ratio (HR) for melanoma of 1.22 (95% CI: 1.19 to 1.25) when adjusting for sex, age and SES characteristics. The HR for melanoma in relative UVR (per 1 standard deviation) was larger for men (HR = 1.26; 95% CI: 1.21 to 1.30) than for women (HR = 1.17; 95% CI: 1.13 to 1.22). INTERPRETATION: Ambient summer UVR is associated with a greater risk of melanoma among the white population, even in a country where most people live within a narrow latitudinal belt. A stronger association between melanoma and ambient UVR was evident among men and among people of lower SES.

Sun exposure, sun protection and sunburn among Canadian adults.

BACKGROUND: Ultraviolet radiation (UVR) exposure and a history of sunburn are important risk factors for skin cancer. Sunburn is more common among men, younger age groups, and people in higher income households. Sun protection measures also vary by sex, age, and socioeconomic characteristics. Associations between ambient UVR and sunburn and sun safety measures have not been quantified. DATA AND METHODS: A total of 53,130 respondents aged 18 or older answered a Canadian Community Health Survey (CCHS) module on sun safety, which was administered in six provinces from 2005 to 2014. The module contained questions about sunburn, time in the sun, and sun protection. These respondents were linked to an ambient erythemal UVR dataset representing the June-to-August mean. Descriptive statistics and logistic regression were used to examine associations between population characteristics, sunburn, sun safety, time in the sun, and ambient UVR. RESULTS: Sunburn was reported by 33% of respondents and was more common among men, younger age groups, people who were not members of visible minorities, residents of higher income households, and individuals who were employed. On a typical summer day, a larger percentage of women than men sought shade and wore sunscreen, whereas a larger percentage of men wore a hat or long pants. As ambient summer UVR increased, women were more likely to apply sunscreen to their face, seek shade, or wear a hat (OR~1.02 to 1.09 per increase of 187 J/m² of erythemally-weighted UVR, or 5.4% of the mean); these associations were not observed among men. INTERPRETATION: Findings related to sunburn and sun protection were similar to those of previous studies. The association between ambient UVR and women's precautionary measures suggests that information about UVR may influence their decision to protect their skin.

Risk estimates of mortality attributed to low concentrations of ambient fine particulate matter in the Canadian community health survey cohort.

BACKGROUND: Understanding the shape of the relationship between long-term exposure to ambient fine particulate matter (PM2.5) concentrations and health risks is critical for health impact and risk assessment. Studies evaluating the health risks of exposure to low concentrations of PM2.5 are limited. Further, many existing studies lack individual-level information on potentially important behavioural confounding factors. METHODS: A prospective cohort study was conducted among a subset of participants in a cohort that linked respondents of the Canadian Community Health Survey to mortality (n = 299,500) with satellite-derived ambient PM2.5 estimates. Participants enrolled between 2000 and 2008 were followed to date of death or December 31, 2011. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mortality attributed to PM2.5 exposure, adjusted for individual-level and contextual covariates, including smoking behaviour and body mass index (BMI). RESULTS: Approximately 26,300 non-accidental deaths, of which 32.5 % were due to circulatory disease and 9.1 % were due to respiratory disease, occurred during the follow-up period. Ambient PM2.5 exposures were relatively low (mean = 6.3 µg/m(3)), yet each 10 µg/m(3) increase in exposure was associated with increased risks of non-accidental (HR = 1.26; 95 % CI: 1.19-1.34), circulatory disease (HR = 1.19; 95 % CI: 1.07-1.31), and respiratory disease mortality (HR = 1.52; 95 % CI: 1.26-1.84) in fully adjusted models. Higher hazard ratios were observed for respiratory mortality among respondents who never smoked (HR = 1.97; 95 % CI: 1.24-3.13 vs. HR = 1.45; 95 % CI: 1.17-1.79 for ever smokers), and among obese (BMI ≥ 30) respondents (HR = 1.76; 95 % CI: 1.15-2.69 vs. HR = 1.41; 95 % CI: 1.04-1.91 for normal weight respondents), though differences between groups were not statistically significant. A threshold analysis for non-accidental mortality estimated a threshold concentration of 0 µg/m(3) (+95 % CI = 4.5 µg/m(3)). CONCLUSIONS: Increased risks of non-accidental, circulatory, and respiratory mortality were observed even at very low concentrations of ambient PM2.5. HRs were generally greater than most literature values, and adjusting for behavioural covariates served to reduce HR estimates slightly.

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

BACKROUND: Fine 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. METHODS: We 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. RESULTS: Glutathione-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. CONCLUSIONS: Our findings suggest that glutathione-related oxidative burden may be more strongly associated with lung cancer mortality than PM2.5 mass concentrations.