Search

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 (PM 2.5 ) and nitrogen dioxide (NO 2 ) 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 NO 2 and PM 2.5, 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: PM 2.5 and NO 2 were positively correlated with each other (r = 0.57). An IQR increase of PM 2.5 (1.9 µg/m 3 ) and NO 2 (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 NO 2 at residence five years earlier (OR = 2.16, 95 % CI: 1.41-3.31), while no association was observed with PM 2.5 (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., NO 2 ), increases the risk of breast cancer in young women., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul J. Villeneuve reports financial support was provided by The Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Striking geographic variations in prostate cancer incidence suggest an aetiological role for spatially-distributed factors. We assessed whether neighbourhood social deprivation, which can reflect limited social contacts, unfavourable lifestyle and environmental exposures, is associated with prostate cancer risk., Methods: In 2005-2012, we recruited 1931 incident prostate cancer cases and 1994 controls in a case-control study in Montreal, Canada. Lifetime residential addresses were linked to an area-based social deprivation index around recruitment (2006) and about 10 years earlier (1996). Logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Men residing in areas characterised by greater social deprivation had elevated prostate cancer risks (ORs of 1.54 and 1.60 for recent and past exposures, respectively; highest vs lowest quintiles), independently from area- and individual-level confounders and screening patterns. The increase in risk with recent high social deprivation was particularly elevated for high-grade prostate cancer at diagnosis (OR 1.87, 95% CI 1.32-2.64). Associations were more pronounced for neighbourhoods with higher proportions of separated/divorced or widowed individuals in the past, and with higher percentages of residents living alone recently., Conclusions: These novel findings, suggesting that neighbourhood-level social deprivation increases the risk of prostate cancer, point out to potential targeted public health interventions., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS 269 ). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS 269 . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS 269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS 269 developed from multi-ancestry GWASs and fine-mapping., Competing Interests: Declaration of interests The authors have no conflicts of interest to disclose., (Copyright © 2023 American Society of Human Genetics. All rights reserved.)

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility., Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry., Design, Setting, and Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry., Outcome Measurements and Statistical Analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness., Results and Limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10 -4 )., Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry., Patient Summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Social isolation has been linked to a poorer prostate cancer prognosis. Little is known about how it could also influence its incidence. We investigated the association between family structure and living arrangements as potential indicators of social isolation, and prostate cancer risk, globally and according to disease aggressiveness. Data from the Prostate Cancer & Environment Study (PROtEuS), a case-control population-based study conducted between 2005 and 2012 in Montreal, Canada, were used. The study population comprised 1931 incident cases of prostate cancer, aged ≤75 years, and 1994 age-matched (±5 years) population controls. In-person interviews collected information on family composition and living arrangements recently and at age 40. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. Single men had an increased risk of high-grade prostate cancer at diagnosis (OR 1.80; 95% CI 1.29-2.51), compared to men currently married or with a partner. Having at least one daughter was associated with a lower risk of aggressive cancer (OR 0.76; 95% CI 0.61-0.96) while no association was found with having son(s). An inverse dose-response relationship was observed between the number of people living with the subject 2 years before diagnosis/interview and prostate cancer risk (p-trend<0.001). These results suggest a protective role of a rich personal environment on the risk of developing prostate cancer. As several of the associations studied here are novel, replication is required., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflict of interests., (Copyright © 2023. Published by Elsevier Inc.)

Volatile organic compounds (VOCs) are components of the complex mixture of air pollutants within cities and can cause various adverse health effects. Therefore, it is necessary to understand their spatial distribution for exposure assessment in epidemiological studies., Objectives: The objective was to model measured concentrations of five VOCs within the city of Montreal, Canada, developing spatial prediction models that can be used in health studies., Methods: We measured concentrations using 3M 3500 Organic Vapor Monitors, over 2-week periods, for three monitoring campaigns between 2005 and 2006 in over 130 locations in the city. Using GC/MSD (Gas Chromatography/Mass Selective Detector), we measured concentrations of benzene, n-decane, ethylbenzene, hexane, and trimethylbenzene. We fitted four different models that combine land-use regression and geostatistical methods to account for the potential spatial structure that remains after accounting for the land-use variables. The fitted models also accounted for possible variations in the concentration of air pollutants across campaigns., Results: The highest concentrations for all VOCs were found in December with hexane being the most abundant followed by ethylbenzene. We obtained predicted surfaces for the VOCs for the three campaigns and mean surfaces across campaigns. We found higher concentrations of some VOCs along highways and in the Eastern part of Montreal, which is a highly industrialized area., Conclusions: Each of the fitted models captured the spatial and across-campaigns variability for each VOC, and we found that different VOCs required different model structures., Competing Interests: S.Z.-M. would like to acknowledge CONACYT, Health Canada, and FRQNT. A.M.S. acknowledges financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada (DiscoveryGrant RGPIN-2017-04999). The other authors have no conflicts to report. This work was funded through a contract with Health Canada under the Addressing Air Pollution Horizontal Initiative program. The original measurements were supported from a grant from the Canadian Institutes for Health Research. Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background and Purpose: The bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of multiple sclerosis (MS) through immunomodulation. Previous studies, presenting some limitations, reported no association. We re-examined this association in a large cohort focusing on relapsing-remitting MS (RRMS)., Methods: The cohort included 400,563 individuals, and was linked with the Quebec provincial BCG vaccination registry and administrative health data. Individuals were followed up from 1983 to 2014 and then within Period 1 (1983-1996) and Period 2 (1997-2014), for the occurrence of MS. Incident MS cases were defined as those with ≥3 hospital or physician claims for MS. Subjects with ≥1 drug reimbursement for MS disease-modifying therapies were classified as RRMS. Cox proportional hazards regression was used to estimate hazard ratios (HRs) over the follow-ups, adjusting for potential confounders. Possible effect modification due to sex was assessed., Results: A total of 178,335 (46%) individuals were BCG vaccinated. There were 274 (0.06%) incident MS cases identified in 1983-1996, and 1433 (0.4%) in 1997-2014. No association was found with RRMS, either in Period 1 (adjusted HR [HR adj ] = 0.96, 95% confidence interval [CI] = 0.63-1.45; 96 cases) or in Period 2 (HR adj  = 1.02, 95% CI = 0.85-1.23; 480 cases). The remaining MS cases, for whom the phenotype was unknown, were positively associated with BCG over the entire follow-up (HR adj  = 1.25, 95% CI = 1.10-1.41; 1131 cases) and in Period 2 (HR adj  = 1.33, 95% CI = 1.17-1.52; 953 cases). No interaction with sex was found., Conclusions: Findings suggest that BCG vaccination does not decrease the risk of RRMS, and that future studies should consider phenotypes of MS., (© 2022 European Academy of Neurology.)

Aims: Bacillus Calmette-Guerin (BCG) vaccination limits blood sugar elevations and autoimmunity. Previous studies focused on type 1 diabetes among children, despite possible effects on other phenotypes later in life. We studied associations between BCG vaccination and type 1, type 2 and latent autoimmune diabetes (LADA) in adulthood., Methods: A 1970-1974 birth cohort was linked with the BCG vaccination registry and administrative health data of Quebec. 396,118 people aged 22-44 years were followed-up for diabetes mellitus (DM) onset. Incident DM cases were subjects with ≥1 hospitalization or ≥2 physician claims related to DM over a 2-year period. Type 1 diabetes, type 2 diabetes, and LADA cases were individuals with ≥1 reimbursement of insulin, oral antidiabetic agent, or both. Cox proportional regressions were used to estimate hazard ratios (HR), adjusting for potential confounders., Results: Forty-four percent of subjects were BCG vaccinated, 88% of these before age 1. For type 1 diabetes, no association was found before 30 years old, but vaccinated subjects had a lower risk of this phenotype after age 30 (HRadj= 0.65, 95% CI: 0.44-0.95). BCG vaccination was associated with a lower risk of type 2 diabetes (HRadj=0.85, 95% CI: 0.79-0.92), whereas no association was observed for LADA (HRadj=1.30, 95% CI: 0.71-2.38). Results did not differ by sex., Conclusions: Early life BCG vaccination was associated with lower risks of both type 1 and type 2 diabetes from early to middle adulthood, but not of LADA. Future studies should explore these long-term associations, while distinguishing diabetes phenotypes., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets., Methods: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured., Results: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively., Conclusions: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations., (© 2022. The Author(s).)

Background: Mixed models are used to correct for confounding due to population stratification and hidden relatedness in genome-wide association studies. This class of models includes linear mixed models and generalized linear mixed models. Existing mixed model approaches to correct for population substructure have been previously investigated with both continuous and case-control response variables. However, they have not been investigated in the context of extreme phenotype sampling (EPS), where genetic covariates are only collected on samples having extreme response variable values. In this work, we compare the performance of existing binary trait mixed model approaches (GMMAT, LEAP and CARAT) on EPS data. Since linear mixed models are commonly used even with binary traits, we also evaluate the performance of a popular linear mixed model implementation (GEMMA)., Results: We used simulation studies to estimate the type I error rate and power of all approaches assuming a population with substructure. Our simulation results show that for a common candidate variant, both LEAP and GMMAT control the type I error rate while CARAT's rate remains inflated. We applied all methods to a real dataset from a Québec, Canada, case-control study that is known to have population substructure. We observe similar type I error control with the analysis on the Québec dataset. For rare variants, the false positive rate remains inflated even after correction with mixed model approaches. For methods that control the type I error rate, the estimated power is comparable., Conclusions: The methods compared in this study differ in their type I error control. Therefore, when data are from an EPS study, care should be taken to ensure that the models underlying the methodology are suitable to the sampling strategy and to the minor allele frequency of the candidate SNPs., (© 2022. The Author(s).)

Background: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ., Materials and Methods: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC., Results: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings., Conclusion: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

According to current US recommendations, the choice to undergo screening for prostate cancer should be an individual one, after considering with a clinician the balance of harms and benefits, and the values and preferences in the decision. Social relationships may influence such a decision. The purpose of this scoping review was to map the evidence on the association between social relationships and prostate cancer screening in the epidemiological literature and to highlight gaps in knowledge. We performed a systematic search of all relevant articles published up to February 1st 2021. We used variations in search terms related to prostate cancer screening, as well as indicators of social relationships. From the 908 records identified, 19 studies, published in 2007-2020, were included. The most common indicator of social relationships was marital status. Overall, married men or men with a partner had a higher screening uptake. Church attendance, based on studies conducted in the United states, was also associated with screening. We found little evidence linking screening with parenthood status or perceived social support. The overall evidence points to a potentially causal association between social relationships and men's decision to undergo prostate cancer screening. More research is needed on the underlying mechanisms and on the potential barriers and facilitators for screening., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of type 1 diabetes through non-specific immunomodulation. Previous epidemiological studies, presenting some limitations, report no association. We examined this association of early life BCG vaccination and age at vaccination with type 1 diabetes incidence in adolescence in a large representative cohort in Quebec. The cohort included 387,704 individuals born in Quebec between 1970 and 1974 whose BCG vaccination status was determined from a provincial registry. Individuals were followed up from 1985 to their 19th birthday (maximum to 1993) for their use of physician services. Individuals were defined as type 1 diabetes cases if they had ≥4 related physician claims over a 2-year period, with at least 30 days between two claims. Cox proportional hazards regression was used to estimate the association of BCG vaccination and age at vaccination with type 1 diabetes. Covariates were selected based on a directed acyclic graph. Interaction according to sex was evaluated. A total of 178,133 (45.9%) individuals were vaccinated and 442 (0.11%) incident cases of type 1 diabetes were identified. The risk of type 1 diabetes was similar in vaccinated compared with unvaccinated individuals (adjusted hazard ratio = 1.06 [95% CI: 0.88-1.29]). There was no association with age at vaccination, and results did not differ by sex (Interaction, p = 0.60). Our results suggest that BCG vaccination does not prevent type 1 diabetes in adolescence., (Copyright © 2021 Elsevier Inc. All rights reserved.)

While being in a committed relationship is associated with a better prostate cancer prognosis, little is known about how marital status relates to its incidence. Social support provided by marriage/relationship could promote a healthy lifestyle and an increased healthcare seeking behavior. We investigated the association between marital status and prostate cancer risk using data from the PRACTICAL Consortium. Pooled analyses were conducted combining 12 case-control studies based on histologically-confirmed incident prostate cancers and controls with information on marital status prior to diagnosis/interview. Marital status was categorized as married/partner, separated/divorced, single, or widowed. Tumours with Gleason scores ≥ 8 defined high-grade cancers, and low-grade otherwise. NCI-SEER's summary stages (local, regional, distant) indicated the extent of the cancer. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CI) for the association between marital status and prostate cancer risk, adjusting for potential confounders. Overall, 14,760 cases and 12,019 controls contributed to analyses. Compared to men who were married/with a partner, widowed men had an OR of 1.19 (95% CI 1.03-1.35) of prostate cancer, with little difference between low- and high-grade tumours. Risk estimates among widowers were 1.14 (95% CI 0.97-1.34) for local, 1.53 (95% CI 1.22-1.92) for regional, and 1.56 (95% CI 1.05-2.32) for distant stage tumours. Single men had elevated risks of high-grade cancers. Our findings highlight elevated risks of incident prostate cancer among widowers, more often characterized by tumours that had spread beyond the prostate at the time of diagnosis. Social support interventions and closer medical follow-up in this sub-population are warranted., (© 2021. Springer Nature B.V.)

Background: There remains controversy as to whether cell phones cause cancer. We evaluated whether temporal changes in cell phone use and the incidence of glioma in Canada were consistent with the hypothesis of an increased risk., Design: We used data from the Canadian Cancer Registry to calculate annual incidence rates for glioma between 1992 and 2015. The annual number of new cell phone subscribers was determined using national industry statistics. The number of newly diagnosed gliomas was compared to the predicted number by applying risks from epidemiological studies to age-specific population estimates. Specifically, we calculated the "predicted" number of incident gliomas by determining the annual prevalence of cell phone users and years of use. These estimates were multiplied by the corresponding risk estimates to determine the predicted number of gliomas., Results: The number of cellular subscriptions in Canada increased from nil in the early-1980s to approximately 29.5 million in 2015. In contrast, age-standardized glioma incidence rates remained stable between 1992 and 2015. When applying risk estimates from i) a recent pooled analysis of Swedish case-control studies, ii) the 13 country INTERPHONE study, and iii) more recent results from data collected from the Canadian component of the INTERPHONE these risks overestimated the observed number of glioma cases diagnosed in Canada in 2015 by 50%, 86%, and 63%, respectively., Interpretation: Predictions of glioma incidence counts using estimates of the relative risk of glioma due to cell phone use from case-control studies over-estimated the incidence rates of glioma in Canada. The absence of an elevation in incidence rates of glioma in conjunction with marked increases in cell phone use suggests that there may not be a causal link between cellphones and glioma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer., Methods: In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands - each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman's Standard International Occupational Prestige Scale) were affected by adjustment for the job indices., Results: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56-1.93), PSI 1.33 (95% CI 1.17-1.51)] and women [PHI 1.62 (95% CI 1.24-2.11), PSI 1.31 (95% CI 1.09-1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32-1.58) to 1.30 (95% CI 1.17-1.45)], but not PSI., Conclusions: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.

Purpose: Greater body fatness is a probable cause of advanced prostate cancer (PCa). Body fat distribution and timing of exposure may be relevant. We investigated associations between body size trajectories and PCa incidence in a population-based case-control study in Montreal, Canada., Methods: Cases (n = 1,931), aged ≤ 75 years, were diagnosed with PCa in 2005-2009; 1,994 controls were selected from the electoral list. Interviews were conducted to assess body mass index (BMI) and Stunkard's silhouette at ages 20, 40, 50, 60 years, and before interview. Current waist and hip circumferences were measured, and a predictive model estimated waist circumference in the past. BMI and waist circumference trajectories were determined to identify subgroups. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between anthropometric indicators and PCa., Results: Subjects with a current BMI ≥ 30 kg/m 2 had a lower risk of overall PCa (OR 0.71, 95% CI 0.59-0.85). Associations with adult BMI followed similar trends for less and more aggressive tumors, with stronger inverse relationships in early adulthood. Contrastingly, current waist circumference ≥ 102 cm was associated with elevated risk of high-grade PCa (OR 1.33, 95% CI 1.03-1.71). Men with increasing BMI or waist circumference adult trajectories had a lower risk of PCa, especially low-grade, than those in the normal-stable range. This was especially evident among men in the obese-increase group for BMI and waist circumference., Conclusion: Abdominal obesity increased the risk of aggressive PCa. The inverse relationship between body size trajectories and PCa may reflect PSA hemodilution, lower detection, and/or a true etiological effect.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS 1 ) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS 2 (PHS 1 , adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS 2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10 -180 ). Comparing the 80 th /20 th PHS 2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS 2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans., (© 2020 Union for International Cancer Control.)

Objectives: If prostate cancer screening practices relate to occupation, this would have important implications when studying the aetiological role of workplace exposures on prostate cancer. We identified variations in screening by occupation among men in Montreal, Canada (2005-2012)., Methods: Prostate specific antigen testing and digital rectal examination (ever-screened and frequency of screening, previous five years) were examined among population controls from the Prostate Cancer & Environment Study . Face-to-face interviews elicited lifestyle and occupational histories. Multivariable logistic regression was used to estimate the odds of ever-screening for the longest-held occupation, adjusting for potential confounders. Negative binomial models were used to examine relationships with screening frequency., Results: Among 1989 controls, 81% reported ever having had a prostate specific antigen test, and 77% a digital rectal examination. Approximately 40% of men reported having a prostate specific antigen test once a year, on average. Compared with those in management or administrative jobs, men in primary industry (odds ratio 0.26, 95% confidence interval 0.10-0.65), construction (0.44, 0.25-0.79), machining (0.45, 0.21-0.97), and teaching (0.37, 0.20-0.70) were less likely to have undergone prostate specific antigen screening. Results were similar when considering the most recent job., Conclusions: Our findings highlight substantial variations in prostate cancer screening by occupation. Men in occupations where carcinogen exposures are more common are less likely to participate in prostate screening activities. This could be an important source of bias, and occupational studies of prostate cancer should account for screening practices.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes. Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations. Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m 3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined. Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

This study aimed at characterizing anthropometric indicators that can be used as alternatives to measurements for assessing overall obesity over adulthood and abdominal obesity among men. We used data from a population-based case-control study of prostate cancer conducted in Montreal, Canada in 2005-2012. It included men aged ≤ 75 years, 1872 of which were newly diagnosed with prostate cancer, and 1918 others randomly selected from the electoral list. In-person interviews elicited reports of height as well as of weight, pants size and Stunkard's silhouette at 5 time points over adulthood, i.e., for the ages of 20, 40, 50 and 60 years, if applicable, and at the time of interview. Waist and hip circumferences were measured by interviewers following a validated protocol. Analyses were conducted on the overall sample of 3790 subjects, after having confirmed that results did not differ according to disease status. Stunkard's silhouette scale proved to be an easy-to-administer tool that reflects well reported body mass index, either recently or decades in the past among adult males. It was discriminatory enough to classify individuals according to commonly-used obesity categories. We observed that a model including age, reported pants size, silhouette and weight can reasonably predict current abdominal obesity. In conclusion, alternative anthropometric indicators can serve as valuable means to assess overall and abdominal obesity when measurements cannot be envisaged in the context of epidemiological studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

This study describes the association between dietary patterns and prostate cancer (PCa) risk in a population-based case-control study conducted in Montreal, Canada (2005-2012). Cases ( n = 1919) were histologically confirmed, aged ≤75 years. Concomitantly, controls ( n = 1991) were randomly selected from the electoral list and frequency-matched to cases by age (±5 years). During face-to-face interviews, a 63-item food frequency questionnaire focusing on the two years before diagnosis/interview was administered. Three dietary patterns were identified from principal component analysis. Unconditional logistic regression estimated the association between dietary patterns and PCa, adjusting for age, ethnicity, education, family history, and timing of last PCa screening. When comparing scores in the highest vs. lowest quartiles, the Healthy Eating pattern was associated with a decreased risk of overall PCa (Odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61, 0.93); this association was stronger for high-grade cancers (OR = 0.66, 95% CI = 0.48, 0.89). By contrast, the Western Sweet and Beverages pattern was associated with an elevated risk of overall PCa (OR = 1.35, 95% CI = 1.10, 1.66). The Western Salty and Alcohol pattern was not associated with PCa risk. These findings suggest that some dietary patterns influence PCa development.

Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate-to-vigorous recreational physical activity (MVPA) in relation to ovarian cancer risk. In a population-based case-control study conducted in Montreal, Canada from 2011 to 2016 (485 cases and 887 controls), information was collected on lifetime participation in various recreational physical activities, which was used to estimate MVPA for each participant. MVPA was represented as average energy expenditure over the lifetime and in specific age-periods in units of metabolic equivalents (METs)-hours per week. Odds ratios (OR) and 95% confidence intervals (CI) for the relation between average MVPA and ovarian cancer risk were estimated using multivariable logistic regression models. Confounding was assessed using directed acyclic graphs combined with a change-in-estimate approach. The adjusted OR (95% CI) for each 28.5 MET-hr/week increment of lifetime recreational MVPA was 1.11 (0.99-1.24) for ovarian cancer overall. ORs for individual age-periods were weaker. When examined by menopausal status, the OR (95% CI) for lifetime MVPA was 1.21 (1.00-1.45) for those diagnosed before menopause and 1.04 (0.89-1.21) for those diagnosed postmenopausally. The suggestive positive associations were stronger for invasive ovarian cancers and more specifically for high-grade serous carcinomas. These results do not support a reduced ovarian cancer risk associated with MVPA., (© 2019 UICC.)

Lymphoma etiology remains ill-defined, but immune factors seem to play a major role. The Bacillus Calmette-Guérin (BCG) vaccine, a non-specific stimulator of the cellular immune response, could influence lymphoma risk. Previous studies addressing this issue showed conflicting results. In this study, we performed a systematic review and meta-analysis to synthesize the epidemiological evidence. We conducted a systematic search of all relevant articles in PubMed, Embase, Library and Archives Canada, and Cochrane databases, up to November 1 st 2018. A total of 11 studies were included. Each study was summarized, methodological quality was assessed by independent evaluators, and a consensus score was generated. Heterogeneity and publication bias were evaluated. Summary odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) by either a fixed effect (FE) or a random effect (RE) model depending on heterogeneity. In this meta-analysis, BCG vaccination was not associated with HL (FE summary OR = 1.10; 95 % CI 0.93-1.30), but positively associated with NHL (RE summary OR = 1.20; 95 % CI 1.01-1.43). However, when restricting to higher quality studies, no association was found between BCG vaccination and either HL (RE summary OR = 0.97; 95 % CI 0.67-1.43) or NHL (RE summary OR = 1.15; 95 % CI 0.84-1.59). Overall, our findings do not support that BCG vaccination is associated with lymphoma risk. Yet, lack of statistical power and relatively high heterogeneity among studies prevent us from making definitive conclusions. Future studies investigating this issue are needed, using robust methodology., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Silica and asbestos are recognized lung carcinogens. However, their role in carcinogenesis at other organs is less clear. Clearance of inhaled silica particles and asbestos fibers from the lungs may lead to translocation to sites such as the bladder where they may initiate carcinogenesis. We used data from a Canadian population-based case-control study to evaluate the associations between these workplace exposures and bladder cancer., Methods: Data from a population-based case-control study were used to characterize associations between workplace exposure to silica and asbestos and bladder cancer among men. Bladder cancer cases (N = 658) and age-frequency matched controls (N = 1360) were recruited within the National Enhanced Cancer Surveillance System from eight Canadian provinces (1994-97). Exposure concentration, frequency and reliability for silica and asbestos were assigned to each job, based on lifetime occupational histories, using a combination of job-exposure profiles and expert review. Exposure was modeled as ever/never, highest attained concentration, duration (years), highest attained frequency (% worktime) and cumulative exposure. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using adjusted logistic regression., Results: A modest (approximately 20%) increase in bladder cancer risk was found for ever having been exposed to silica, highest attained concentration and frequency of exposure but this increase was not statistically significant. Relative to unexposed, the odds of bladder cancer were 1.41 (95%CI: 1.01-1.98) times higher among men exposed to silica at work for ≥27 years. For asbestos, relative to unexposed, an increased risk of bladder cancer was observed for those first exposed ≥20 years ago (OR:2.04, 95%CI:1.25-3.34), those with a frequency of exposure of 5-30% of worktime (OR:1.45, 95%CI:1.06-1.98), and for those with < 10 years of exposure at low concentrations (OR:1.75, 95%CI:1.10-2.77) and the lower tertile of cumulative exposure (OR:1.69, 95%CI:1.07-2.65). However, no clear exposure-response relationships emerged., Conclusions: Our results indicate a slight increase in risk of bladder cancer with exposure to silica and asbestos, suggesting that the effects of these agents are broader than currently recognized. The findings from this study inform evidence-based action to enhance cancer prevention efforts, particularly for workers in industries with regular exposure.

We studied the association between food intake, based on the extent of processing, and prostate cancer risk in a population-based case-control study conducted in Montreal, Canada in 2005-2012. Incident prostate cancer cases ( n = 1919) aged ≤75 years were histologically confirmed. Population controls ( n = 1991) were randomly selected from the electoral list and frequency-matched to cases by age (±5 years). A 63-item food frequency questionnaire focusing on the two years prior to diagnosis/interview was administered by interviewers. The NOVA classification was used to categorize foods based on processing level. Unconditional logistic regression estimated the association between food intake and prostate cancer risk, adjusting for age, education, ethnicity, family history, and timing of last prostate cancer screening. Consumption of unprocessed or minimally processed foods showed a slight, inverse association (Odd ratio [OR] 0.86, 95% confidence interval [CI] 0.70-1.07; highest vs. lowest quartile) with prostate cancer. An increased risk was observed with higher intake of processed foods (OR 1.29, 95%CI 1.05-1.59; highest vs. lowest quartile), but not with consumption of ultra-processed food and drinks. The associations with unprocessed/minimally processed foods and processed foods were slightly more pronounced for high-grade cancers (ORs 0.80 and 1.33, respectively). Findings suggest that food processing may influence prostate cancer risk., Competing Interests: The authors declare no conflict of interest.

The CANJEM job-exposure matrix compiles expert evaluations of 31 673 jobs from four population-based case-control studies conducted in Montreal. For each job, experts had derived indices of intensity, frequency, and probability of exposure to 258 agents. CANJEM summarizes the exposures assigned to jobs into cells defined by occupation/industry, agent, and period. Some cells may, however, be less populated than others, resulting in uncertain estimates. We developed a modelling framework to refine the estimates of sparse cells by drawing on information available in adjacent cells. Bayesian hierarchical logistic and linear models were used to estimate the probability of exposure and the geometric mean (GM) of frequency-weighted intensity (FWI) of cells, respectively. The hierarchy followed the Canadian Classification and Dictionary of Occupations (CCDO) classification structure, allowing for exposure estimates to be provided across occupations (seven-digit code), unit groups (four-digit code), and minor groups (three-digit code). The models were applied to metallic dust, formaldehyde, wood dust, silica, and benzene, and four periods, adjusting for the study from which jobs were evaluated. The models provided estimates of probability and FWI for all cells that pulled the sparsely populated cells towards the average of the higher-level group. In comparisons stratified by cell sample size, shrinkage of the estimates towards the group mean was marked below 5 jobs/cell, moderate from 5 to 9 jobs/cell, and negligible at ≥10 jobs/cell. The modelled probability of three-digit cells were slightly smaller than their descriptive estimates. No systematic trend in between-study differences in exposure emerged. Overall, the modelling framework for FWI appears to be a suitable approach to refine CANJEM estimates. For probability, the models could be improved by methods better adapted to the large number of cells with no exposure., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Most risk factors for lymphoma identified so far relate to immunosuppression, but its aetiology remains unclear., Objectives: We investigated whether Bacillus Calmette-Guérin (BCG) vaccination is associated with lymphoma, overall and separately for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL)., Methods: A cohort of 400 611 subjects born in the province of Québec, Canada, between 1970 and 1974 was used. Information on BCG vaccination was extracted from the Quebec BCG Vaccination Registry. Lymphomas cases were individuals who had ≥2 health encounters, medical visits or hospitalizations, for lymphoma within 2 months or who were identified through the Quebec Tumor Registry. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CI), adjusting for potential confounders., Results: A total of 178 335 (46.0%) subjects were BCG-vaccinated, and 1478 (0.38%) cases of lymphomas were ascertained. Amongst them, 922 were identified as NHL and 421 as HL. After adjustment, no association was observed between BCG vaccination and either lymphoma (any type) (HR = 1.03, 95% CI: 0.96-1.11) or NHL (HR = 0.99, 95% CI: 0.86-1.13). For HL, nonproportional hazards were observed. Before the age of 18, the risk of HL was elevated amongst vaccinated individuals (HR = 2.26, 95% CI: 1.39-3.69). However after 18 years of age, no association was found (HR = 0.93, 95% CI: 0.75-1.15)., Conclusion: Bacillus Calmette-Guérin vaccination may increase the risk of HL before 18 years of age, but residual confounding cannot entirely be excluded. Given the benefits of BCG vaccination, these results need to be reproduced in other populations before firm conclusions can be drawn., (© 2019 The Association for the Publication of the Journal of Internal Medicine.)

Background: Work histories generally cover all jobs held for ≥1 year. However, it may be time and cost prohibitive to conduct a detailed exposure assessment for each such job. While disregarding short-term jobs can reduce the assessment burden, this can be problematic if those jobs contribute important exposure information towards understanding disease aetiology., Objective: To characterize short-term jobs, defined as lasting more than 1 year, but less than 2 years, in a population-based study conducted in Montreal, Canada., Methods: In 2005-2012, we collected work histories for some 4000 participants in a case-control study of prostate cancer. Overall, subjects had held 19 462 paid jobs lasting ≥1 year, including 3655 short-term jobs. Using information from interviews and from the Canadian Classification and Dictionary of Occupations, we characterized short-term jobs and compared them to jobs held ≥2 years., Results: Short-term jobs represented <4% of subjects' work years on average. Forty-five per cent of subjects had at least one short-term job; of these, 49% had one, 24% had two, and 27% had at least three. Half of all short-term jobs had been held before the age of 24. Short-term jobs entailed more often exposure to fumes, odours, dust, and/or poor ventilation than longer jobs (17 versus 13%), as well as outdoor work (10 versus 5%) and heavy physical activity (16 versus 12%)., Conclusions: Short-term jobs occurred often in early careers and more frequently entailed potentially hazardous exposures than longer-held jobs. However, as they represented a small proportion of work years, excluding them should have a marginal impact on lifetime exposure assessment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: While the expert-based occupational exposure assessment approach has been considered the reference method for retrospective population-based studies, its implementation in large study samples has become prohibitive. To facilitate its application and improve upon it we developed, in the context of a Montreal population-based study of prostate cancer (PROtEuS), a hybrid approach combining job-exposure profiles (JEPs) summarizing expert evaluations from previous studies and expert review. We aim to describe the hybrid expert method and its impacts on the exposures assigned in PROtEuS compared to those from a previous study coded using the traditional expert method., Methods: Applying the hybrid approach, experts evaluated semi-quantitative levels of confidence, concentration and frequency of exposure to 313 agents for 16,065 jobs held by 4005 subjects in PROtEuS. These assessments were compared to those from a different set of jobs coded in an earlier study of lung cancer, conducted on the same study base, for 90 blue-collar occupations and 203 agents. Endpoints evaluated included differences in the number of exposures and in the distribution of ratings across jobs, and the within-occupation variability in exposure., Results: Compared to jobs from the lung cancer study, jobs in PROtEuS had on average 0.3 more exposures. PROtEuS exposures were more often assigned definite confidence ratings, but concentration and frequency levels tended to be lower. The within-occupation variability in ratings assigned to jobs were lower in PROtEuS jobs for all metrics. This was particularly evident for concentration, although considerable variability remained with over 40% of occupation/agent cells in PROtEuS exposed at different levels. The hybrid approach reduced coding time by half, compared to the traditional expert assessment., Conclusions: The new hybrid expert approach improved on efficiency and transparency, and resulted in greater confidence in assessments, compared to the traditional expert method applied in an earlier study involving a similar set of jobs. Assigned ratings were more homogeneous with the hybrid approach, possibly reflecting clearer guidelines for coding, greater coherence between experts and/or reliance on summaries of past assessments. Nevertheless, significant within-occupation variability remained with the hybrid approach, suggesting that experts took into account job-specific factors in their assessments.

Objectives: The CANJEM general population job-exposure matrix summarizes expert evaluations of 31 673 jobs from four population-based case-control studies of cancer conducted in Montreal, Canada. Intensity in each CANJEM cell is represented as relative distributions of the ordinal (low, medium, high) ratings of jobs assigned by the experts. We aimed to apply quantitative concentrations to CANJEM cells using Canadian historical measurements from the Canadian Workplace Exposure Database (CWED), taking exposure to wood dust as an example., Methods: We selected 5170 personal and area wood dust measurements from 31 occupations (2011 Canadian National Occupational Classification) with a non-zero exposure probability in CANJEM between 1930 and 2005. The measurements were taken between 1981 and 2003 (median 1989). A Bayesian hierarchical model was applied to the wood dust concentrations with occupations as random effects, and sampling duration, year, sample type (area or personal), province, and the relative proportion of jobs exposed at medium and high intensity in CANJEM cells as fixed effects., Results: The estimated geometric mean (GM) concentrations for a CANJEM cell with all jobs exposed at medium or high intensity were respectively 1.3 and 2.4 times higher relative to a cell with all jobs at low intensity. An overall trend of -3%/year in exposure was observed. Applying the model estimates to all 198 cells in CANJEM with some exposure assigned by the experts, the predicted 8-hour, personal wood dust GM concentrations by occupation for 1989 ranged from 0.48 to 1.96 mg m-3., Conclusions: The model provided estimates of wood dust concentrations for any CANJEM cell with exposure, applicable for quantitative risk assessment at the population level. This framework can be implemented for other agents represented in both CANJEM and CWED.

Background: Many previous studies on asthma phenotypes were conducted in selected clinical populations and overlooked changes throughout the life course., Objective: To identify asthma phenotypes based on use of health services for allergic diseases in 3 life periods and document transitions among phenotypes across life periods., Methods: In a population-based cohort of 78,211 individuals born in 1974 in the province of Québec, Canada, we documented medical visits and hospitalizations for asthma and other allergic diseases until 1994. Phenotypes based on clusters of health services use in childhood (8-12 years of age), adolescence (13-17 years of age), and young adulthood (18-20 years of age) were identified using a hierarchical method among 9,989 individuals (12.8%) who had at least one health encounter for asthma during follow-up. Population-level probabilities of transitioning among phenotypes were estimated in the full study population., Results: In the subset with asthma, 6 phenotypes were identified during both childhood and young adulthood and 7 during adolescence. The most common phenotype was no asthma or allergic diseases: 58% in childhood, 42% in adolescence, and 54% in adulthood. The second most common was the mild asthma and no allergic diseases phenotype, representing 36%, 31%, and 21%, respectively, in these 3 periods. In the study population, 87% of the individuals remained in the no asthma phenotype group during the follow-up. Most individuals in the asthma phenotypes transitioned over time., Conclusion: Our study uniquely contributes to a better understanding, at the population level, of the manifestations and transitions in asthma phenotypes during the life course., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The purpose of this study was to describe dietary patterns among 1636 French-speaking men residing in Montreal, Canada and to assess sociodemographic and lifestyle characteristics of men adhering to the dietary patterns identified. Participants were population controls from the Prostate Cancer and Environment Study, a case-control study conducted between 2006 and 2011 in Montreal. Information on diet was collected using a food frequency questionnaire, and principal component analysis, a data-driven method and a posteriori method, was used to identify dietary patterns. Three dietary patterns were identified; Healthy, Modified Western - Salty and Modified Western - Sweet patterns accounted for 7.0%, 5.4%, and 3.2% of the variance, respectively. The Healthy pattern was characterized by consumption of fruits, vegetables, vegetable soup, chicken, fish and seafood, cheese, rice, yogurt, and wine. The Modified Western - Salty pattern included high loadings for beef, pork, chicken, hot-dogs or sausages, cold cuts, bacon, barbecue cooking, meat slightly blackened, potatoes, pasta with tomato sauce, pizza, pastries, dark carbonated soft drinks, ice cream, and white bread. The third pattern, labelled as Modified Western - Sweet, had high loadings of cookies, muffins, cakes, pastries, pies, ice cream, fruits and vegetables. In multivariate analyses, the Healthy pattern was positively associated with higher income and education, moderate recreational physical activity and less heavy smoking, and inversely associated with French ancestry. The Modified Western - Salty pattern was positively associated with French, other European, and Latino ancestries, and with married and common-law relationships. Finally, the Modified Western - Sweet pattern was more common among men of French ancestry and users of vitamin/mineral supplements. The Healthy pattern has been frequently observed in other Western populations, but the other two are described for the first time in a study population of men.

Background: Previous studies on socioeconomic position (SEP) and risk of prostate cancer (PCa) have produced contradictory results. Most measured SEP only once during the individuals' life span. The aim of the study was to identify life course models that describe best the relationship between SEP measured during childhood/adolescence, early- and late-adulthood, and risk of PCa overall as well as according to tumor aggressiveness at diagnosis. Methods: We used data from a population-based case-control study of PCa conducted in the predominantly French-speaking population in Montreal, Canada. Cases ( n = 1,930) with new, histologically-confirmed PCa were ascertained across hospitals deserving the French-speaking population in 2005-2009. Controls ( n = 1,991), selected from Quebec's list of French-speaking electors, were frequency-matched to cases (±5 years). In-person interviews collected information on socio-demographic and lifestyle characteristics, and a complete occupational history. Measures of SEP during childhood/adolescence included parents' ownership of a car and father's longest occupation, while the subject's first and longest occupations were used to indicate early- and late-adulthood SEP, respectively. We used the Bayesian relevant life course exposure model to investigate the relationship between lifelong SEP and PCa risk. Results: Cumulative exposure to disadvantageous SEP was associated with about a 50% increase in odds of developing PCa. Late-adulthood SEP was identified as a sensitive period for aggressive PCa. Childhood/adolescence SEP based on parents' ownership of a car was associated with non-aggressive PCa. Associations were independent from PCa screening. Conclusion: Disadvantageous SEP over the life course was associated with higher PCa incidence, with consistent evidence of sensitive time periods for cancer aggressiveness. The mechanisms through which disadvantageous SEP relates to PCa risk need to be further elucidated.

Introduction: Kidney cancer is the fifth most common incident cancer in Canadian men. Diesel and gasoline exhausts are common workplace exposures that have been examined as risk factors for non-lung cancer sites, including the kidney, but limitations in exposure assessment methods have contributed to inconsistent findings. The objective of this study was to assess the relationship between occupational gasoline and diesel engine exhausts and the risk of kidney cancer in men., Methods: The National Enhanced Cancer Surveillance System (NECSS) is a Canadian population-based case-control study conducted in 1994-1997. Incident kidney cancer cases were identified using provincial registries, while the control series was identified through random-digit dialing, or provincial administrative databases. Self-reported questionnaires were used to obtain information on lifetime occupational history and cancer risk factors. Two hygienists, blinded to case status, coded occupational histories for diesel and gasoline exhaust exposures using concentration, frequency, duration, and reliability. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) separately by exhaust type. The separate and combined impacts of both engine exhausts were also examined. ORs were adjusted for age, province, body mass index, occupational secondhand smoke exposure, and education., Results: Of the kidney cancer cases (n = 712), 372 (52%) had exposure to both exhausts at some point, and 984 (40%) of the controls (n = 2457) were ever exposed. Workers who had ever been exposed to engine exhausts were more likely to have kidney cancer than those who were never exposed (OR diesel = 1.23, 95% CI = 0.99-1.53; OR gasoline = 1.51, 95% CI = 1.23-1.86). Exposure to gasoline exhaust was consistently associated with kidney cancer in a dose-response manner (P value for trends in highest attained and cumulative exposure both <0.0001). Those men with high cumulative exposure to both gasoline and diesel exhaust had a 76% increased odds of kidney cancer (95% CI = 1.27-2.43)., Conclusions: This study provides evidence that occupational gasoline, and to a lesser extent, diesel exhaust exposure may increase the risk of kidney cancer.

Objectives: We developed a job-exposure matrix called CANJEM using data generated in population-based case-control studies of cancer. This article describes some of the decisions in developing CANJEM, and some of its performance characteristics., Methods: CANJEM is built from exposure information from 31673 jobs held by study subjects included in our past case-control studies. For each job, experts had evaluated the intensity, frequency, and likelihood of exposure to a predefined list of agents based on jobs histories and descriptions of tasks and workplaces. The creation of CANJEM involved a host of decisions regarding the structure of CANJEM, and operational decisions regarding which parameters to present. The goal was to produce an instrument that would provide great flexibility to the user. In addition to describing these decisions, we conducted analyses to assess how well CANJEM covered the range of occupations found in Canada., Results: Even at quite a high level of resolution of the occupation classifications and time periods, over 90% of the recent Canadian working population would be covered by CANJEM. Prevalence of exposure of specific agents in specific occupations ranges from 0% to nearly 100%, thereby providing the user with basic information to discriminate exposed from unexposed workers. Furthermore, among exposed workers there is information that can be used to discriminate those with high exposure from those with low exposure., Conclusions: CANJEM provides good coverage of the Canadian working population and possibly that of several other countries. Available in several occupation classification systems and including 258 agents, CANJEM can be used to support exposure assessment efforts in epidemiology and prevention of occupational diseases.

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

Background: Little is known about occupational risk factors for meningioma., Objectives: To study whether risk of meningioma is associated with several occupational exposures, including selected combustion products, dusts and other chemical agents., Methods: The INTEROCC study was an international case-control study of brain cancer conducted in seven countries. Data collection by interview included lifetime occupational histories. A job exposure matrix was used to derive estimates of exposure for the 12 agents. ORs for ever versus never exposed and for exposure-response using duration of exposure and cumulative exposure were derived using conditional logistic regression stratified by sex, age group, country/region, adjusted for education., Results: These analyses included 1906 cases and 5565 controls. For 11 of the 12 agents, no excess risk was found for ever exposed. For ever exposure to oil mists, an elevated OR of 1.57 (95% CI 1.10 to 2.22, 51 exposed cases) was found. Statistically significant exposure-response relationships were observed with cumulative exposure (p=0.01) and duration of exposure (p=0.04). Among women, there were also significant trends for cumulative and duration of exposure to asbestos and excesses in the highest exposure categories for formaldehyde., Conclusions: Most agents examined did not provoke excess risks of meningioma. The main finding from this study is that it is the first study to identify a statistical association between exposure to oil mists and meningioma. This may be a chance finding or could be due to confounding with iron exposure and further research is required to understand whether the relationship is causal., Competing Interests: Competing interests: MCT reports personal fees from ICF, outside this work. DK reports to serving as Chief Risk Scientist and CEO at Risk Sciences International (http://www.risksciences.com), a Canadian company established in 2006 in partnership with the University of Ottawa conducting work in risk assessment, management and communication of health and environmental risks and their broader impacts on both public and private interests. He also holds an Industrial Research Chair in Risk Science under a peer-reviewed university-industry partnership programme administered by the Natural Sciences and Engineering Research Council of Canada., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We undertook a re-analysis of the Canadian data from the 13-country case-control Interphone Study (2001-2004), in which researchers evaluated the associations of mobile phone use with the risks of brain, acoustic neuroma, and parotid gland tumors. In the main publication of the multinational Interphone Study, investigators concluded that biases and errors prevented a causal interpretation. We applied a probabilistic multiple-bias model to address possible biases simultaneously, using validation data from billing records and nonparticipant questionnaires as information on recall error and selective participation. In our modeling, we sought to adjust for these sources of uncertainty and to facilitate interpretation. For glioma, when comparing those in the highest quartile of use (>558 lifetime hours) to those who were not regular users, the odds ratio was 2.0 (95% confidence interval: 1.2, 3.4). After adjustment for selection and recall biases, the odds ratio was 2.2 (95% limits: 1.3, 4.1). There was little evidence of an increase in the risk of meningioma, acoustic neuroma, or parotid gland tumors in relation to mobile phone use. Adjustments for selection and recall biases did not materially affect interpretation in our results from Canadian data., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is scant information as to whether traffic-related air pollution is associated with the incidence of breast cancer. Nitrogen dioxide (NO 2 ) and ultrafine particles (UFPs, <0.1µm), are two pollutants that capture intra-urban variations in traffic-related air pollution and may also be associated with incidence., Methods: We conducted a population-based, case-control study of street-level concentrations of NO 2 and UFPs and incident postmenopausal breast cancer in Montreal, Canada. Incident cases were identified between 2008 and 2011 from all but one hospital that treated breast cancer in the Montreal area. Population controls were identified from provincial electoral lists of Montreal residents and frequency-matched to cases using 5-year age groups. Concentrations of NO 2 and UFPs were estimated using two separate land-use regression models. Exposures were assigned to residential locations at the time of recruitment, and we identified residential histories of women who had lived in these residences for 10 years or more. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models adjusting for individual-level and ecological covariates. We assessed the functional form of NO 2 and UFP exposures using natural cubic splines., Results: We found that the functional form of the response functions between incident postmenopausal breast cancer and concentrations of NO 2 and UFPs were consistent with linearity. For NO 2 , we found increasing risks of breast cancer for all subjects combined and stronger associations when analyses were restricted to those women who had lived at their current address for 10 years or more. Specifically, the OR, adjusted for personal covariates, per increase in the interquartile range (IQR=3.75 ppb) of NO 2 was 1.08 (95%CI: 0.92-1.27). For women living in their homes for 10 years or more, the adjusted OR was 1.17 (95%CI: 0.93-1.46; IQR=3.84 ppb); for those not living at that home 10 years before the study, it was 0.93 (95%CI: 0.64, 1.36; IQR=3.65 ppb). For UFPs, the ORs were lower than for NO 2 , with little evidence of association in any of the models or sub-analyses and little variability in the ORs (about 1.02 for an IQR of ~3500cm -3 ). On the other hand, we found higher ORs amongst cases with positive oestrogen and progesterone receptor status; namely for NO 2 , the OR was 1.13 (95%CI: 0.94-1.35) and for UFPs it was 1.05 (95%CI: 0.96-1.14)., Conclusions: Our findings suggest that exposure to ambient NO 2 and UFPs may increase the risk of incident postmenopausal breast cancer especially amongst cases with positive oestrogen and progesterone receptor status., (Copyright © 2017. Published by Elsevier Inc.)

Background: In the province of Québec, Canada, the Bacillus Calmette-Guérin (BCG) vaccine was offered to newborns and school-age children from the 1950s to mid-1970s in an organized tuberculosis prevention program., Objective: We aimed to describe the annual rates of skin test administration, proportion of skin tests that were positive, and rates of BCG vaccination from 1956 to 1974 according to age, sex, and administrative region., Methods: For rates, numerators were extracted from the Québec BCG Vaccination Registry whereas population denominators were obtained from the Canadian Census and governmental publications. Time trends were assessed with linear regression., Results: A total of 2,755,336 skin tests and 2,531,366 BCG vaccinations were administered. Yearly rates of skin tests, routinely administered before vaccination among all except newborns, were highest among children aged 5-9 (9.3 per 100) and 10-14years (7.9 per 100). The proportion of positive skin tests varied greatly by age, ranging from 10.2% among children <1year to 67.2% among adults ≥20years. The vast majority of individuals who had a negative skin test were subsequently vaccinated, whereas those with a positive result were not, as per recommended guidelines. The average annual vaccination rate was highest among children aged <1year (43.8 per 100) and 5-9year-olds (6.9 per 100). There were salient differences in immunization rates, including positive skin tests and vaccinations, across administrative regions but no difference by sex., Conclusion: This is the first comprehensive description of the tuberculosis prevention program in Québec which offered free, non-mandatory BCG vaccination. Our results confirm that the targeted groups, newborns and school-age children, were preferentially reached. Socioeconomic, demographic, and organizational factors may explain regional differences in immunization rates. Beyond presenting a historical context for this vaccination campaign, our findings are relevant to contemporary uses of the Québec BCG Vaccination Registry in epidemiological research., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Hormone-related factors have been associated with ovarian cancer, the strongest being parity and oral contraceptive use. Given reductions in birth rates and increases in oral contraceptive use over time, associations in more recent birth cohorts may differ. Furthermore, consideration of ovarian cancer heterogeneity (i.e., Type I/II invasive cancers) may contribute to a better understanding of etiology. We examined hormone-related factors in relation to ovarian cancer risk overall, for Type I and Type II cancers, as well as borderline tumors., Methods: A population-based case-control study was carried out in Montreal, Canada from 2011 to 2016, including 496 cases and 908 controls. For each hormone-related variable, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for ovarian cancer overall, and using polytomous logistic regression for associations by tumor behavior and ovarian cancer type., Results: Parity was inversely associated with risk overall and by tumor behavior and type, with a stronger OR (95% CI) for Type I [0.09 (0.04-0.24) for ≥3 full-term births vs. nulliparity] vs. Type II [0.66 (0.43-1.02)] invasive cancers; the OR (95% CI) for borderline tumors was 0.41 (0.22-0.77). Oral contraceptive ever use was not associated with risk overall, but ≥10 years of use vs. never use reduced risk, particularly for invasive cancers. A history of endometriosis was most strongly associated with Type I cancers. Associations with other factors were less clear., Conclusions: These results suggest that associations with some hormone-related factors may differ between borderline and invasive Type I and II ovarian cancers.

Background: The association between perceived workplace psychological stress, over the entire work career, and cancer among men has never been assessed. This was explored in the context of a population-based case-control study conducted in Montreal, Canada., Methods: 3103 incident cancer cases (11 types) diagnosed in 1979-1985 and 512 population controls were interviewed. Subjects described in detail each job held during their lifetime, including the occurrence of stress, and its reason. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between perceived workplace stress and its duration, and each cancer site, adjusting for lifestyle and occupational factors., Results: Employment in at least one stressful job was associated with increased odds of cancers of the lung (OR=1.33, 95% CI: 1.01-1.75), colon (OR=1.51, 95% CI: 1.15-1.98), bladder (OR=1.37, 95% CI: 1.03-1.81), rectal (OR=1.52, 95% CI: 1.10-2.10), and stomach (OR=1.53, 95% CI: 1.08-2.15). A duration-response trend was found for cancers of the lung, colon, rectum, stomach, and for NHL. Subjects reported changes in stress level over their career. Perceived stress was ascribed to several sources, including high demand and time pressure, financial issues, job insecurity, and hazardous conditions., Conclusion: Prolonged exposure to perceived stress at work was associated with greater odds of cancer at 5 out of 11 sites. While over reporting of stress by cases cannot be fully ruled out, these associations, if substantiated, would bear important public health significance. Prospective studies building on detailed stress assessment protocols considering all sources and changes over the career are necessary., (Copyright © 2016 Elsevier Inc. All rights reserved.)