Sex differences in the inflammation-depression link: A systematic review and meta-analysis.

Major Depressive Disorder (MDD) is a heterogeneous disorder that affects twice as many women than men. Precluding advances in more tailored and efficacious treatments for depression is the lack of reliable biomarkers. While depression is linked to elevations in inflammatory immune system functioning, this relationship is not evident among all individuals with depression and may vary based on symptom subtypes and/or sex. This systematic review and meta-analysis examined whether inflammatory immune peripheral markers of depression are sex-specific. PRISMA guidelines were followed for the systematic review, and a comprehensive search strategy that identified studies from PubMed and PsycInfo was applied. Studies were included if they reported C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and/or IL-1ß for males and/or females among depressed and healthy adults. We identified 23 studies that satisfied these inclusion criteria. Random-effects meta-analysis models were fit, and measures of association were summarized between levels of circulating markers of inflammation in depressed and healthy males and females. Sex-based analyses revealed elevated levels of CRP among females with depression (Cohen's d = 0.19) relative to their healthy counterparts (p = 0.02), an effect not apparent among males (Cohen's d = -0.01). Similarly, levels of IL-6 were increased among females with depression compared to healthy controls (Cohen's d = 0.51; p = 0.04), but once again this was not found among males (Cohen's d = 0.16). While TNF-α levels were elevated among individuals with depression compared to controls (p = 0.01), no statistically significant sex differences were found. The meta-analysis for IL-1ß resulted in only three articles, and thus, results are presented in the supplemental section. This meta-analysis advances our understanding of the unique involvement of inflammatory biomarkers in depression among men and women, which may help inform more tailored sex-specific treatment approaches in the future.

Residential exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and incident breast cancer among young women in Ontario, Canada.

BACKGROUND: Air pollution has been classified as a human carcinogen based largely on findings for respiratory cancers. Emerging, but limited, evidence suggests that it increases the risk of breast cancer, particularly among younger women. We characterized associations between residential exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and breast cancer. Analyses were performed using data collected in the Ontario Environmental Health Study (OEHS). METHODS: The OEHS, a population-based case-control study, identified incident cases of breast cancer in Ontario, Canada among women aged 18-45 between 2013 and 2015. A total of 465 pathologically confirmed primary breast cancer cases were identified from the Ontario Cancer Registry, while 242 population-based controls were recruited using random-digit dialing. Self-reported questionnaires were used to collect risk factor data and residential histories. Land-use regression and remote-sensing estimates of NO2 and PM2.5, respectively, were assigned to the residential addresses at interview, five years earlier, and at menarche. Logistic regression was used to estimate odds ratios (OR) and their 95 % confidence intervals (CI) in relation to an interquartile range (IQR) increase in air pollution, adjusting for possible confounders. RESULTS: PM2.5 and NO2 were positively correlated with each other (r = 0.57). An IQR increase of PM2.5 (1.9 µg/m3) and NO2 (6.6 ppb) at interview residence were associated with higher odds of breast cancer and the adjusted ORs and 95 % CIs were 1.37 (95 % CI = 0.98-1.91) and 2.33 (95 % CI = 1.53-3.53), respectively. An increased odds of breast cancer was observed with an IQR increase in NO2 at residence five years earlier (OR = 2.16, 95 % CI: 1.41-3.31), while no association was observed with PM2.5 (OR = 0.96, 95 % CI 0.64-1.42). CONCLUSIONS: Our findings support the hypothesis that exposure to ambient air pollution, especially those from traffic sources (i.e., NO2), increases the risk of breast cancer in young women.

Ambient polycyclic aromatic hydrocarbon exposure and breast cancer risk in a population-based Canadian case-control study.

PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) represent a class of ubiquitous pollutants recognized as established human carcinogens and endocrine-disrupting chemicals. PAHs have seldom been modeled at the population-level in epidemiological studies. Fluoranthene is a prevalent PAH in urban settings and correlates with the occurrence of other PAHs. The purpose of this study was to evaluate associations between long-term residential exposure to ambient PAHs and breast cancer risk, both pre- and post-menopausal, in Canada. METHODS: Using the National Enhanced Cancer Surveillance System (NECSS), a national-scale Canadian population-based case-control study, annual fluoranthene exposures were estimated using the GEM-MACH-PAH chemical transport model on the basis of geocoded residential histories throughout a 20-year exposure window. Odds ratios (ORs) and 95% confidence intervals (CIs) controlling for potential confounders were estimated using logistic regression. Separate analyses were conducted for Ontario and national samples given a finer-resolution exposure surface and additional risk factor information available for Ontario. RESULTS: Positive associations were observed between fluoranthene exposure and premenopausal breast cancer, with inconsistent findings for postmenopausal breast cancer. For premenopausal breast cancer, adjusted ORs of 2.48 (95% CI: 1.29, 4.77) and 1.59 (95% CI: 1.11, 2.29) were observed when comparing the second highest category of exposure to the lowest, among the Ontario and national samples, respectively. For postmenopausal breast cancer, adjusted ORs were 1.10 (95% CI: 0.67, 1.80) and 1.33 (95% CI: 1.02, 1.73). Associations for the highest level of exposure, across both samples and menopausal strata, were non-significant. CONCLUSION: This study provides support for the hypothesis that ambient PAH exposures increase the risk of premenopausal breast cancer.

Updated Analysis of Radon Exposure and Lung Cancer Mortality in the Cohort of Newfoundland Fluorspar Miners (1950-2016).

The commercial mining of fluorspar in St. Lawrence Newfoundland began in 1933. Miners who worked underground were exposed to high levels of radon progeny, especially before ventilation was introduced into the mines in 1960. The mean cumulative radon exposure for underground miners in this cohort was 380.9 working level months (WLM). A series of studies of this cohort have characterized the increased risks of lung cancer mortality due to radon. We have extended the follow-up of this cohort an additional 15 years to provide additional insights on the risks of low levels of radon exposure, and the modifying effects of time since exposure, age at first exposure, attained age, duration of exposure, and cigarette smoking. The cohort consisted of 1,735 underground and 315 male surface miners who, combined, accrued 81,650 person-years of follow-up. The mortality experience of the cohort was determined from 1950-2016 through record linkage to Canadian national death data. Individual-level estimates of exposure to radon progeny, in WLMs, were determined for each year of employment. We compared the mortality experience of the underground miners to Newfoundland men using the standardized mortality ratio (SMR). Poisson regression models were fit to estimate excess relative risks (ERR) per 100 WLM. There were 236 lung cancer deaths identified, and of these, 221 occurred among underground workers. The SMR for lung cancer among underground miners compared to Newfoundland men was 2.67 (95% CI: 2.33, 3.04). The ERR per 100 WLM for lung cancer mortality, assuming a 5-year exposure lag, was 0.41 (95% CI: 0.23, 0.59). Attained age and time since exposure were important modifiers to the radon-lung cancer relationship. The joint relationship between smoking and radon on lung cancer risk was sub-additive, however, the smoking data were limited and available for only half of the cohort.

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000-2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. METHODS: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. RESULTS: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6-1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9-28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7-35.0) for NMSC deaths and 30.4 % (UR 29.0-31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180-19,740) and 0.5 million DALYs (UR 0.4-0.5). Men and older age groups carried larger burden. Over 2000-2019, attributable deaths and DALYs almost doubled. CONCLUSIONS: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.

Exposure to low-dose radiation in occupational settings and ischaemic heart disease: a systematic review and meta-analysis.

Ionising radiation is a human carcinogen, but the evidence is less clear that exposure to low-dose ionising radiation (LDIR) increases the risk of adverse cardiovascular outcomes. We synthesised the literature of chronic occupational exposure to LDIR and cardiovascular disease, particularly for ischaemic heart disease (IHD).The literature search was conducted using three databases including studies published between 1990 and 2022. A quality assessment of the studies was completed using the Office of Health and Assessment and Translation Risk of Bias Rating Tool. We conducted meta-analyses for IHD mortality using random effects models using measures of excess relative risk per sievert (ERR/Sv) obtained from internal cohort comparisons, as well as with standardised mortality ratios (SMRs) from external cohort comparisons.We identified 2189 articles, and of these, 26 provided data on IHD and were retained. Most studies were classified as having a 'moderate' level of risk of bias. Fourteen and 10 studies reporting external radiation doses were included in meta-analyses using SMR and ERR/Sv, respectively. The meta-summary SMR was 0.81 (95% CI 0.74 to 0.89) with evidence of reduced risk but high heterogeneity across studies. For internal cohort measures, the summary ERR/Sv for a lagged exposure of 10 years was 0.10 (95% CI 0.01 to 0.20) with low heterogeneity. The subgroup analysis by lagged exposure time showed the strongest association were for the 15 and 20 years lag.Our findings suggest that occupational exposure to LDIR increases the risk IHD mortality and highlight the relevance of internal cohort comparisons.

Exposure to Ionizing Radiation and Risk of Dementia: A Systematic Review and Meta-Analysis.

The number of people living with dementia is rising globally as life expectancy increases. Dementia is a multifactorial disease. Due to the ubiquity of radiation exposure in medical and occupational settings, the potential association between radiation and dementia, and its subtypes (Alzheimer's and Parkinson's disease), is of particular importance. There has also been an increased interest in studying radiation induced dementia risks in connection with the long-term manned space travel proposed by The National Aeronautics and Space Administration (NASA). Our aim was to systematically review the literature on this topic, and use meta-analysis to generate a summary measure of association, assess publication bias and explore sources of heterogeneity across studies. We identified five types of exposed populations for this review: 1. survivors of atomic bombings in Japan; 2. patients treated with radiation therapy for cancer or other diseases; 3. occupationally exposed workers; 4. those exposed to environmental radiation; and 5. patients exposed to radiation from diagnostic radiation imaging procedures. We included studies that considered incident or mortality outcomes for dementia and its subtypes. Following PRISMA guidelines, we systematically searched the published literature indexed in PubMed between 2001 and 2022. We then abstracted the relevant articles, conducted a risk-of-bias assessment, and fit random effects models using the published risk estimates. After we applied our eligibility criteria, 18 studies were identified for review and retained for meta-analysis. For dementia (all subtypes), the summary relative risk was 1.11 (95% CI: 1.04, 1.18; P = 0.001) comparing individuals receiving 100 mSv of radiation to those with no exposure. The corresponding summary relative risk for Parkinson's disease incidence and mortality was 1.12 (95% CI 1.07, 1.17; P <0.001). Our results provide evidence that exposure to ionizing radiation increases the risk of dementia. However, our findings should be interpreted with caution due to the small number of included studies. Longitudinal studies with improved exposure characterization, incident outcomes, larger sample size, and the ability to adjust for effects of potential confounders are needed to better assess the possible causal link between ionizing radiation and dementia.

Circulatory system disease mortality and occupational exposure to radon progeny in the cohort of Newfoundland Fluorspar Miners between 1950 and 2016.

OBJECTIVES: Exposure to ionizing radiation may increase the risk of circulatory diseases, including heart disease. A limited number of cohort studies of underground miners have investigated these associations. We previously reported a positive but non-statistically significant association between radon progeny and heart disease in a cohort of Newfoundland fluorspar miners. In this study, we report updated findings that incorporate 15 additional years of follow-up. METHODS: The cohort included 2050 miners who worked in the fluorspar mines from 1933 to 1978. Statistics Canada linked the personal identifying data of the miners to Canadian mortality data to identify deaths from 1950 to 2016. We used previously derived individual-level estimates of annual radon progeny exposure in working-level months. Cumulative exposure was categorized into quantiles. We estimated relative risks and their 95% confidence intervals using Poisson regression for deaths from circulatory, ischemic heart disease and acute myocardial infarction. Relative risks were adjusted for attained age, calendar year, and the average number of cigarettes smoked daily. RESULTS: Relative to the Newfoundland male population, the standardized mortality ratio for circulatory disease in this cohort was 0.82 (95% CI 0.74-0.91). Those in the highest quantile of cumulative radon progeny exposure had a relative risk of circulatory disease mortality of 1.03 (95% CI 0.76-1.40) compared to those in the lowest quantile. The corresponding estimates for ischemic disease and acute myocardial infarction were 0.99 (95% CI 0.66-1.48), and 1.39 (95% CI 0.84-2.30), respectively. CONCLUSIONS: Our findings do not support the hypothesis that occupational exposure to radon progeny increases the risk of circulatory disease.

Physical activity and the risk of non-Hodgkin lymphoma subtypes: A pooled analysis.

Non-Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case-control studies to examine the association between moderate-to-vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T-cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study-specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case-control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.

Low-dose ionizing radiation and adverse birth outcomes: a systematic review and meta-analysis.

OBJECTIVE: Ionizing radiation is a human carcinogen, and there is evidence that exposure to low-dose ionizing radiation increases the risk of adverse birth outcomes. METHODS: We undertook a systematic review and meta-analysis to synthesize the research of maternal and paternal exposure to low-dose radiation on low birth weight, miscarriage, pre-term delivery, and stillbirth. Our literature search used four databases (PubMed, Environmental Index, GeoBASE, and the Cumulative Index to Nursing and Allied Health Literature). We included study populations exposed to occupational and medical sources of radiation, nuclear disasters, and those living near nuclear power plants. We considered papers published between January 1st, 1990, and June 30th, 2021. The quality of the studies was assessed, and we performed meta-analysis using random effects models to generate summary measures of association. Forest plots were created to assess the heterogeneity in these measures, and funnel plots were used to assess publication bias. RESULTS: Overall, 26 studies were identified, and these yielded measures of association from 10, 11, and 8 studies for low birth weight, miscarriage, and stillbirth outcomes, respectively. It was not possible to perform meta-analyses for pre-term delivery due to a small number of studies. The meta-analysis summary relative risk (RR) of having a low-birth-weight infant among those ever exposed to radiation relative to those unexposed, after adjusting for publication bias, was 1.29 (95% CI 0.97-1.73). The corresponding risk estimates for miscarriage and stillbirth were 1.15 (95% CI 1.02-1.30), and 1.19 (95% CI 0.98-1.45), respectively. CONCLUSIONS: Our findings suggest that ionizing radiation increases the risk of adverse birth outcomes. Future work should strive to provide data needed to better understand the shape of the exposure-response curve.

Protective effects of physical activity on mental health outcomes during the COVID-19 pandemic.

The COVID-19 pandemic has been linked with increased reports of depression, anxiety, and stress. Stay-at-home directives during the pandemic-imposed lifestyle changes, including eating and sedentary behaviors that can further undermine mental health outcomes. Physical activity is a vital component for metabolic health, as well as for mental health by serving as an active coping strategy to manage stress and promote resilience. Global reports of increased sedentary leisure behaviors have been associated with feelings of depression and anxiety, but it unclear whether the relationship between physical activity and depression or anxiety persists over time. In this longitudinal study, we investigated (i) whether physical activity at the onset of the pandemic was related to feelings of depression or anxiety over time and (ii) whether this relationship was mediated by stress appraisals during the pandemic. We surveyed 319 adults living in Canada or the United States to assess physical activity, stress appraisals, and mental health outcomes at two time points over a 6-month period. We found a reduction in leisure-time physical activity that was linked to subsequent feelings of depression. Furthermore, individuals with lower levels of physical activity were more likely to appraise their COVID-19 situation to be uncontrollable at pandemic onset and as the pandemic continued. Stress appraisals of threat and uncontrollability were also positively related to feelings of depression. Modelling these three factors together showed that appraising a situation as uncontrollable mediated the relationship between initial physical activity and subsequent depressive feelings. Although correlational, these data highlight the protective role of leisure-time physical activity against worsened mental health outcomes during periods of prolonged stress.

Ambient air pollution and prostate cancer risk in a population-based Canadian case-control study.

Ambient air pollution is a human carcinogen and a possible risk factor for prostate cancer. Methods: We investigated associations between ambient concentrations particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) and incident prostate cancer in a Canadian case-control study. Between 1994 and 1997, cases were identified from provincial cancer registries, and a population-based series of controls was recruited. Among men 50 years of age or older, risk factor and residential history data (1975 to 1994) were collected from 1,420 prostate cancer cases and 1,424 controls. Three methods were used to estimate the residential mean exposure to PM2.5 and NO2 during this period: (1) satellite-derived observations; (2) satellite-derived observations scaled with historical fixed-site measurements; and (3) a national land-use regression (LUR) model. Odds ratios (ORs) and their 95% confidence intervals (CIs) in relation to interquartile range (IQR) increases in PM2.5 and NO2 were estimated using logistic regression, adjusting for personal and contextual factors. Results: We found positive associations between exposure to PM2.5 and NO2 over the previous 20 years and prostate cancer. An IQR increase in PM2.5 (3.56 µg/m3 for satellite and 4.48 µg/m3 for scaled satellite observations) yielded ORs of 1.28 (95% CI = 1.07, 1.52) and 1.20 (95% CI = 1.03, 1.40), respectively. For NO2, IQR increases (1.45 ppb for satellite, 15.18 ppb for scaled satellite-derived information, and 15.39 ppb for the national LUR) were associated with ORs of 1.09 (95% CI = 0.95, 1.24), 1.21 (95% CI = 1.02, 1.43), and 1.19 (95% CI = 1.03, 1.38), respectively. Conclusions: Our findings support the hypothesis that ambient air pollution increases the risk of prostate cancer.

Family History and Risk of Bladder Cancer: An Analysis Accounting for First- and Second-degree Relatives.

Although evidence suggests that a positive family history of bladder cancer in first-degree relatives is an important risk factor for bladder cancer occurrence, results remain unclear. The influence of family history of nonbladder cancers and more distant relatives on bladder cancer risk is inconsistent. This research, therefore, aims to increase the understanding of the association between family history and bladder cancer risk based on worldwide case-control studies. In total 4,327 cases and 8,948 non-cases were included. Pooled ORs, with corresponding 95% confidence intervals (CI), were obtained using multilevel logistic regression models, adjusted by age, sex, ethnicity, smoking status, and smoking pack-years. The results show bladder cancer risk increased by having a first- or second-degree relative affected with bladder cancer (OR, 2.72; 95% CI, 1.55-4.77 and OR, 1.71; 95% CI, 1.22-2.40, respectively), and nonurologic cancers (OR, 1.61; 95% CI, 1.19-2.18). Moreover, bladder cancer risk increased by number of cancers affected first-degree relatives (for 1 and >1 first-degree relatives: OR, 1.42; 95% CI, 1.02-2.04; OR, 2.67; 95% CI, 1.84-3.86, respectively). Our findings highlight an increased bladder cancer risk for a positive bladder cancer family history in first- and second-degree relatives, and indicate a possible greater effect for an increment of numbers of affected relatives. PREVENTION RELEVANCE: This study found a positive association between family history and bladder cancer in first- and second-degree relatives, with an added effect attributed to smoking. Given the detriments of bladder cancer, at-risk individuals should receive family history screening and tobacco cessation and avoidance counseling.

Ambient air pollution and inflammatory effects in a Canadian pregnancy cohort.

BACKGROUND: Epidemiologic studies have consistently reported associations between air pollution and pregnancy outcomes including preeclampsia and gestational diabetes. However, the biologic mechanisms underlying these relationships remain unclear as few studies have collected relevant biomarker data. We examined relationships between ambient PM2.5 and NO2 with markers of inflammation during pregnancy in a prospective cohort of Canadian women. METHODS: We analyzed data from 1170 women enrolled in the Maternal-Infant Research on Environmental Chemicals study. Daily residential PM2.5 and NO2 exposures during pregnancy were estimated using satellite-based and land-use regression models and used to create 14-day and 30-day exposure windows before blood-draw. Inflammatory markers C-reactive protein, interleukin-6, interleukin-8, and tumor necrosis factor-α were measured in third trimester plasma samples. Multivariable linear regression was used to estimate associations for an interquartile range (IQR) increase in PM2.5 and NO2 and markers of inflammation, while adjusting for individual-level confounders. RESULTS: Fourteen-day (IQR: 6.85 µg/m3) and 30-day (IQR: 6.15 µg/m3) average PM2.5 exposures before blood-draw were positively associated with C-reactive protein after adjustment for covariates (24.6% [95% CI = 9.4, 41.9] and 17.4% [95% CI = 1.0, 35.0] increases, respectively). This association was found to be robust in several sensitivity analyses. Neither PM2.5 nor NO2 exposures were associated with interleukin-6, interleukin-8, or tumor necrosis factor-α. CONCLUSION: Exposure to ambient PM2.5 is positively associated with maternal inflammatory pathways in late pregnancy. This may contribute to positive associations between ambient PM2.5 and risk of adverse pregnancy outcomes.

Estimating the future cancer management costs attributable to modifiable risk factors in Canada.

OBJECTIVES: An estimated 33-37% of incident cancers in Canada are attributable to modifiable risk factors. Interventions targeting these risk factors would minimize the substantial health and economic burdens Canadians face due to cancer. We estimate the future health and economic burden of cancer in Canada by incorporating data from the Canadian Population Attributable Risk of Cancer (ComPARe) study into OncoSim, a web-based microsimulation tool. METHODS: Using the integrated OncoSim population attributable risk and population impact measures, we evaluated risk factor-targeted intervention scenarios implemented in 2020, assuming the targeted risk factor prevalence reduction would be achieved by 2032 with a 12-year latency period. RESULTS: We estimate that smoking will be the largest contributor to cancer-related costs, with a cost of CAD $44.4 billion between 2032 and 2044. An estimated CAD $3.3 billion of the cost could be avoided with a 30% reduction in smoking prevalence by 2022. Following smoking, the next highest cancer management costs are associated with inadequate physical activity and excess body weight, accounting for CAD $10.7 billion ($2.7 billion avoidable) and CAD $9.8 billion ($3.2 billion avoidable), respectively. Avoidable costs for other risk factors range from CAD $90 million to CAD $2.5 billion. CONCLUSION: Interventions targeting modifiable cancer risk factors could prevent a substantial number of incident cancer cases and billions of dollars in cancer management costs. With limited budgets and rising costs in cancer care in Canada, these simulation models and results are valuable for researchers and policymakers to inform decisions and prioritize and evaluate intervention programs.

RéSUMé: OBJECTIFS: Il est estimé que de 33 % à 37 % des cancers incidents au Canada sont imputables à des facteurs de risque modifiables. Des interventions ciblant ces facteurs de risque réduiraient le fardeau sanitaire et économique considérable du cancer dans la population canadienne. Nous avons estimé le futur fardeau sanitaire et économique du cancer au Canada en intégrant les données de l'étude ComPARe (Canadian Population Attributable Risk of Cancer) dans l'outil de microsimulation en ligne OncoSim. MéTHODE: À l'aide des indicateurs d'impact dans la population et du risque attribuable dans la population intégrés dans OncoSim, nous avons évalué des scénarios d'intervention mis en œuvre en 2020 axés sur les facteurs de risque, en partant de l'hypothèse que la réduction de la prévalence des facteurs de risque ciblés serait atteinte d'ici 2032 avec une période de latence de 12 ans. RéSULTATS: Nous estimons que le tabagisme sera le facteur qui contribuera le plus aux coûts du cancer, avec un coût de 44,4 milliards $ CA entre 2032 et 2044. Il est estimé qu'une part de 3,3 milliards $ CA de ce coût pourrait être évitée en réduisant de 30 % la prévalence du tabagisme d'ici 2022. Après le tabagisme, les coûts de prise en charge du cancer les plus élevés sont associés à l'inactivité physique et au surpoids, qui représentent respectivement 10,7 milliard $ CA (dont 2,7 milliards $ évitables) et 9,8 milliards $ CA (dont 3,2 milliards $ évitables). Les coûts évitables pour d'autres facteurs de risque vont de 90 millions $ CA à 2,5 milliards $ CA. CONCLUSION: Des interventions ciblant les facteurs de risque de cancer modifiables pourraient prévenir un nombre considérable de cas de cancers incidents et épargner des milliards de dollars en coûts de prise en charge du cancer. Avec les budgets serrés et la hausse des coûts des soins du cancer au Canada, ces modèles de simulation et leurs résultats permettent aux chercheurs et aux responsables des politiques d'éclairer les décisions et de hiérarchiser et d'évaluer les programmes d'intervention.

Estimates of future cancer mortality attributable to modifiable risk factors in Canada.

OBJECTIVES: Modifiable lifestyle, environmental, and infectious risk factors associated with cancer impact both cancer incidence and mortality at the population level. Most studies estimating this burden focus on cancer incidence. However, because these risk factors are associated with cancers of disparate mortality rates, the burden associated with cancer incidence could differ from cancer mortality. Therefore, estimating the cancer mortality attributable to these risk factors provides additional insight into cancer prevention. Here, we estimated future cancer deaths and the number of avoidable deaths in Canada due to modifiable risk factors. METHODS: The projected cancer mortality data came from OncoSim, a web-based microsimulation tool. These data were applied to the methodological framework that we previously used to estimate the population attributable risks and the potential impact fractions of modifiable risk factors on Canadian cancer incidence. RESULTS: We estimated that most cancer deaths will be attributed to tobacco smoking with an average of 27,900 deaths annually from 2024 to 2047. If Canada's current trends in excess body weight continue, cancer deaths attributable to excess body weight would double from 2786 deaths in 2024 to 5604 deaths in 2047, becoming the second leading modifiable cause of cancer death. Applying targets to reduce these risk factors, up to 34,600 cancer deaths could be prevented from 2024 to 2047. CONCLUSION: Our simulated results complement our previous findings on the cancer incidence burden since decreasing the overall burden of cancer will be accelerated through a combination of decreasing cancer incidence and improving survival outcomes through improved treatments.

RéSUMé: OBJECTIFS: Les facteurs de risque modifiables associés au cancer (liés au mode de vie, à l'environnement, aux maladies infectieuses) ont des effets à la fois sur l'incidence du cancer et sur la mortalité par cancer à l'échelle de la population. La plupart des études qui estiment ce fardeau portent sur l'incidence du cancer. Cependant, comme les facteurs de risque susmentionnés sont associés à des cancers dont les taux de mortalité sont disparates, le fardeau associé à l'incidence du cancer pourrait différer de la mortalité par cancer. En conséquence, l'estimation de la mortalité par cancer imputable à ces facteurs de risque pourrait éclairer la prévention du cancer. Nous estimons ici les décès futurs par cancer et le nombre de décès évitables au Canada dus à des facteurs de risque modifiables. MéTHODE: Les données projetées sur la mortalité par cancer proviennent d'OncoSim, un outil de microsimulation en ligne. Elles ont été appliquées au cadre méthodologique que nous avions déjà utilisé pour estimer les risques attribuables dans la population et les fractions de l'incidence potentielle des facteurs de risque modifiables sur l'incidence canadienne du cancer. RéSULTATS: Selon nos estimations, entre 2024 et 2047, la plupart des décès par cancer seront imputés au tabagisme, qui causera en moyenne 27 900 décès par année. Si les tendances actuelles au Canada en matière de surpoids se maintiennent, les décès par cancer attribuables au surpoids doubleraient, passant de 2 786 décès en 2024 à 5 604 en 2047, et le surpoids deviendrait la deuxième cause modifiable de décès par cancer. En appliquant des cibles de réduction de ces facteurs de risque, jusqu'à 34 600 décès par cancer pourraient être évités entre 2024 et 2047. CONCLUSION: Les résultats de notre simulation confirment nos constatations antérieures sur le fardeau de l'incidence du cancer, car la diminution du fardeau global du cancer sera accélérée par une combinaison de la diminution de l'incidence du cancer et de l'amélioration des résultats de survie grâce à l'amélioration des traitements.