Air pollution, clustering of particulate matter components, and breast cancer in the sister study: A U.S.-wide cohort

Abstract

BACKGROUND: Particulate matter (PM) is a complex mixture. Geographic variations in PM may explain the lack of consistent associations with breast cancer. OBJECTIVE: We aimed to evaluate the relationship between air pollution, PM components, and breast cancer risk in a United States-wide prospective cohort. METHODS: We estimated annual average ambient residential levels of particulate matter <2:5 lm and <10 lm in aerodynamic diameter (PM2:5 and PM10, respectively) and nitrogen dioxide (NO2) using land-use regression for 47,433 Sister Study participants (breast cancer–free women with a sister with breast cancer) living in the contiguous United States. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk associated with an interquartile range (IQR) increase in pollutants. Predictive k-means were used to assign participants to clusters derived from PM2:5 component profiles to evaluate the impact of heterogeneity in the PM2:5 mixture. For PM2:5, we investigated effect measure modification by component cluster membership and by geographic region without regard to air pollution mixture. RESULTS: During follow-up (mean = 8:4 y), 2,225 invasive and 623 ductal carcinoma in situ (DCIS) cases were identified. PM2:5 and NO2 were associated with breast cancer overall [HR = 1:05 (95% CI:0.99, 1.11) and 1.06 (95% CI:1.02, 1.11), respectively] and with DCIS but not with invasive cancer. Invasive breast cancer was associated with PM2:5 only in the Western United States [HR = 1:14 (95% CI:1.02, 1.27)] and NO2 only in the Southern United States [HR = 1:16 (95% CI:1.01, 1.33)]. PM2:5 was associated with a higher risk of invasive breast cancer among two of seven identified composition-based clusters. A higher risk was observed [HR = 1:25 (95% CI: 0.97, 1.60)] in a California-based cluster characterized by low S and high Na and nitrate (NO3−) fractions and for another Western United States cluster [HR = 1:60 (95% CI: 0.90, 2.85)], characterized by high fractions of Si, Ca, K, and Al. CONCLUSION: Air pollution measures were related to both invasive breast cancer and DCIS within certain geographic regions and PM component clusters.