Background: The etiology of malignant brain cancer remains largely unknown. The two established risk factors, ionizing radiation and a history of allergies or atopic disease, explain less than 10% of the disease. In 2012, the International Agency for Research on Cancer classified air pollution and particulate matter (PM) as carcinogenic to humans (Group 1). The carcinogenic effects of air pollution may reach the brain via the systemic circulation, crossing the blood-brain barrier. There are increasing concerns about the potential impact of air pollution on outcomes of central nervous system (CNS), including chronic brain inflammation and microglia cell activation, but evidence of its carcinogenic effects is still limited. Methods: Kriging interpolation of air pollution data from monitoring stations were used to estimate long-term exposures of particulate matter pollutants (PM2.5, PM10), gaseous pollutants (oxides of nitrogen (NOx, NO2), ozone (O3), carbon monoxide (CO), and air toxics (benzene) for 103,308 men and women from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993-1996) at age 45-75 through 12/31/2013. Cox proportional hazards models were used to examine the associations between time-varying air pollutant levels and risk of malignant brain cancer (95 men, 116 women) and meningioma (130 men, 425 women) with adjustment for sex, race/ethnicity, neighborhood socioeconomic status, smoking, occupation, and other covariates. Stratified analyses were conducted by sex and race/ethnicity (African Americans, Japanese Americans, Latinos, Whites). Results: In men and women combined, risk of malignant brain cancer appeared to be increased in association with higher exposure to benzene (per 1 ppb HR=1.68, 95% CI:1.00-2.83), O3 (per 10 ppb HR=1.54, 95% CI: 0.95-2.51) and PM10(per 10 μg/m3 HR=1.24, 95% CI: 0.84-1.82) Malignant brain cancer associations with benzene (P=0.002) as well as PM10 (P=0.03) were driven by the results in men, although the interaction by sex did not reach statistical significance. Brain cancers in Latino men and women accounted for about half of the number of malignant brain cancers in this analysis. Subgroup analyses suggested stronger associations of risk of malignant brain cancer and exposure to PM10 (P=0.03), O3 (P=0.01), and benzene (P=0.03) in Latino men but not in Latino women. There were no significant associations between air pollution and risk of meningioma, except for a positive association with O3 exposure (P=0.04) in men. Conclusions: To our knowledge, this is one of the first studies of air pollution and malignant and benign brain cancers to include large numbers of nonwhites and to examine risk patterns by sex. The stronger findings in Latino men and the suggestive male/female differences in results are intriguing as there are parallel sex differences in rates of brain diseases and in survival. Confirmation of these air pollution-brain cancer associations in additional diverse populations is warranted.

Citation Format: Anna H Wu, Jun Wu, Chiuchen Tseng, Juan Yang, Salma Shariff-Marco, Veronica W Setiawan, Shahir Masri, Jennifer Jain, Jacqueline Porcel, Scott Fruin, Timothy Larson, Florence Hofman, Thomas Chen, Loic Le Marchand, Daniel Stram, Beate Ritz, Iona Cheng. Association between outdoor air pollution and risk of malignant and benign brain diseases: The Multiethnic Cohort Study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C068.