Abstract Background: Growing evidence suggests that air pollution may be a risk factor for colorectal cancer (CRC). We examined the association between ambient particulate matter (PM) exposure and CRC risk within the Multiethnic Cohort Study (MEC), representing the first study to include a large sample of racial and ethnic minoritized populations. Methods: The MEC is a prospective study that recruited, from 1993 through 1996, men and women ages 45-75 years largely from five racial and ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and Non-Hispanic White) living in Hawai‘i and California. This study included 98,675 California MEC participants, residing predominately in Los Angeles County. Satellite-based PM2.5 (PM with an aerodynamic diameter <2.5μm) exposures were estimated from a published spatiotemporal model. Kriging interpolation was used to estimate PM10 (PM <10μm) exposures using routine air monitoring data from the US Environmental Protection Agency. Time-varying PM exposures were assessed from time of recruitment through 12/31/2018. Incident invasive CRC cases were identified via linkage with the California Cancer Registry (n=3,217). Cox proportional hazards models were used to examine the association between PM and CRC risk using age as the time metric, with strata defined by age at cohort entry and race and ethnicity, and adjusting for demographic and lifestyle factors. Heterogeneity of the PM-CRC association was assessed by sex, race and ethnicity, and CRC subsite (right colon, left colon, rectum). Results: Risk of CRC increased with PM2.5 (per 10μg/m3 hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.96-1.33) with a larger HR observed among females (HR 1.29, 95% CI 1.03-1.62) than males (HR 0.96, 95% CI 0.76-1.22) (Pheterogeneity=0.24). CRC risk was positively associated with PM2.5 across race and ethnicity (except for African American participants) with the largest HR observed among Latino participants (HR 1.47, 95% CI 1.03-2.08) (Pheterogeneity=0.20). There was no statistically significant heterogeneity of PM2.5 effect by tumor subsite (Pheterogeneity=0.07); although larger HRs were seen for left colon (HR 1.52, 95% CI 1.08- 2.14) and rectal cancers (HR 1.54, 95% CI 1.05-2.25) than right colon cancers (HR 1.09, 95% CI 0.88-1.35). PM10 was not associated with CRC risk (per 10 μg/m3; HR 1.02, 95% CI 0.93-1.22) with no evidence of heterogeneity in associations by sex or race and ethnicity (respective Pheterogeneity 0.75, 0.44). Although HRs for PM10 appeared to differ by CRC subsite (Pheterogeneity=0.03), the 95% CI of these HRs included the null (right HR 0.95, 95% CI 0.84-1.06; left HR 1.13, 95% CI 0.95-1.35; rectal HR 1.18, 95% CI 0.97-1.43). Conclusions: Preliminary findings suggest that PM2.5 exposure is associated with CRC risk with larger associations in females and, possibly, for left colon and rectal cancer. Additional studies are needed to confirm these findings and evaluate the potential biological pathways underlying these associations. Citation Format: Ugonna Ihenacho, Chiuchen Tseng, Jun Wu, Scott Fruin, Timothy V. Larson, Salma Shariff-Marco, Loïc Le Marchand, Daniel O. Stram, Lynne R. Wilkens, Christopher A. Haiman, Beate Ritz, Iona Cheng, Anna H. Wu. Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A048.