Research Postmenopausal Breast Cancer Is Associated with Exposure to Traffic-Related Air Pollution in Montreal, Canada: A Case–Control Study Dan L. Crouse,1 Mark S. Goldberg,2,3 Nancy A. Ross,1 Hong Chen,4 and France Labrèche 5 1Department of Geography, and 2Department of Medicine, McGill University, Montreal, Quebec, Canada; 3Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada; 4Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; 5Département de médecine sociale et préventive et Département de santé environnementale et santé au travail, Université de Montréal, Montreal, Quebec, Canada increased risks. k ey words 6 October 2010] Background : Only about 30% of cases of breast cancer can be explained by accepted risk factors. Occupational studies have shown associations between the incidence of breast cancer and exposure to contaminants that are found in ambient air. o Bjectivs : We sought to determine whether the incidence of postmenopausal breast cancer is associated with exposure to urban air pollution. Msdohte : We used data from a case–control study conducted in Montreal, Quebec, in 1996–1997. Cases were 383 women with incident invasive breast cancer, and controls were 416 women with other incident, malignant cancers, excluding those potentially associated with selected occupational exposures. Concentrations of nitrogen dioxide (NO2) were measured across Montreal in 2005–2006. We developed a land-use regression model to predict concentrations of NO2 across Montreal for 2006, and developed two methods to extrapolate the estimates to 1985 and 1996. We linked these estimates to addresses of residences of subjects at time of interview. We used unconditional logistic regression to adjust for accepted and suspected risk factors and occupational exposures. r esult : For each increase of 5 ppb NO2 estimated in 1996, the adjusted odds ratio was 1.31 (95% confidence interval, 1.00–1.71). Although the size of effect varied somewhat across periods, we found an increased risk of approximately 25% for every increase of 5 ppb in exposure. c onclusion : We found evidence of an association between the incidence of postmenopausal breast cancer and exposure to ambient concentrations of NO2. Further studies are needed to confirm whether NO2 or other components of traffic-related pollution are indeed associated with : air pollution, case–control study, Montreal, nitrogen dioxide, postmenopausal breast cancer. Environ Health Perspect 118:1578–1583 (2010). doi:10.1289/ehp.1002221 [Online New York State (Lewis-Michl et al. 1996), suggested a possible increased risk of breast cancer among postmenopausal women liv- ing near areas characterized by relatively high traffic compared with other areas [adjusted odds ratio (OR), 1.29; 95% confidence inter- val (CI), 0.77–2.15]. In a case–control study in Erie and Niagara Counties, New York State, Bonner et al. (2005) used observations from fixed-site pollution monitors to estimate exposure to total suspended particulates and found that early-life exposures to relatively high concentrations (i.e., > 140 gμ/m 3 ) were associated with an increased risk of devel- oping postmenopausal breast cancer (OR = 2.42; 95% CI, 0.97–6.09) compared with exposure to relatively low concentrations (i.e., < 84 μg/m 3). In a second analysis from that study (Nie et al. 2007), estimates of residential exposures to benzo[a]pyrene, derived from a traffic emissions model, showed an OR of 2.57 (95% CI, 1.16–5.69) for postmenopausal women exposed to higher concentrations at the time of first giving birth compared with those exposed at lower concentrations. They found no evidence that exposures at other periods were associated with increased risk. Furthermore, in analyses stratified by smoking status, statistically significant associations were limited to lifetime nonsmokers. The purpose of the present study was to determine whether the incidence of post- menopausal breast cancer in Montreal, Address correspondence to D.L. Crouse, Department of Geography, McGill University, 805 Sherbrooke St. West, Burnside Hall Rm. 705, Montreal, Quebec, Canada, H3A 2K6. Telephone: (514) 849- 7483. Fax: (514) 398-7437. E-mail: daniel.crouse@ mail.mcgill.ca Supplemental Material is available online (doi:10.1289/ehp.1002221 via http://dx.doi.org/). This study was supported financially through a grant from the Canadian Institutes for Health Research (CIHR). D.C. gratefully acknowledges receipt of a Canada Graduate Scholarship from the CIHR, and M.G. gratefully acknowledges receipt of an Investigator Award from the CIHR. N.R. holds a career award from the Fonds de la Recherche en Santé Québec and gratefully acknowledges receipt of a New Investigator Award from the CIHR (2003–2008). The Canadian Breast Cancer Research Initiative sup- ported the initial case–control study. We thank R. Burnett (Health Canada) for helpful comments. The authors declare they have no actual or potential competing financial interests. Received 28 March 2010; accepted 17 August 2010. ovlume 118 | number 11 | November 2010 • Environmental Health Perspectives Breast cancer has the highest incidence rate of all cancers in women and is the second leading cause of death from cancer in both Canada (Canadian Cancer Society 2009) and the United States (American Cancer Society 2009). Accepted risk factors for breast cancer include genetic mutations, family history of breast cancer, aspects of reproductive history, and lifestyle factors, such as alcohol consump- tion. Only about one-third of new cases of breast cancer are attributable to known risk factors, and much of the etiology remains unexplained (Coyle 2004). There have been consistent findings of higher rates of breast cancer in urban areas compared with rural areas, in both Canada (Bako et al. 1984) and the United States (Hall et al. 2005; Reynolds et al. 2004). Local vehicular traffic is the primary contributor to air pollution in urban areas. Vehicular emissions include gases, particles, volatile organic compounds, and polycyclic aromatic hydrocarbons (PAHs), many of which are accepted or potential carcinogens. Benzene, for example, is present in gasoline, is an accepted human carcinogen (International Agency for Research on Cancer 1987), and has been shown to cause mammary carcino- mas in rodents (Huff et al. 1989; Maltoni 1578 et al. 1988, 1989). Exposure to other aromatic hydrocarbons associated with gasoline, includ- ing kerosene, toluene, and xylenes, has also produced increased rates of mammary cancers in female rats (Maltoni et al. 1997). Aromatic hydrocarbons are lipophilic and may there- fore reach elevated concentrations in breast tissue and promote carcinogenesis in the cells of the breast (Morris and Seifter 1992). We postulated in the mid-1990s (Labrèche and Goldberg 1997) that exposure to organic sol- vents and other lipophilic toxics may cause breast cancer. Santodonato (1997) concluded that, regarding the etiology of human breast cancer, current scientific literature provides “persuasive evidence for the hypothesis that certain carcinogenic PAHs produce a unique duality of pathologic effects encompassing both genotoxic and nongenotoxic components.” Several studies have shown associations between the incidence of breast cancer and occupational exposure to benzene and to PAHs (Gammon et al. 2002; Labrèche et al. 2010; Petralia et al. 1999). Given that these same pollutants are present in vehicular exhaust and thus present in urban air pollution, it is plausi- ble that traffic-related exposures may contrib- ute to the incidence of breast cancer. A study conducted in Nassau and Suffolk Counties,