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 $<2.5\mu m$ and $<10\mu m$ in aerodynamic diameter (${\mathrm{PM}}_{2.5}$ and ${\mathrm{PM}}_{10}$, respectively) and nitrogen dioxide (${\mathrm{NO}}_2$) 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 ${\mathrm{PM}}_{2.5}$ component profiles to evaluate the impact of heterogeneity in the ${\mathrm{PM}}_{2.5}$ mixture. For ${\mathrm{PM}}_{2.5}$, we investigated effect measure modification by component cluster membership and by geographic region without regard to air pollution mixture.

Results: During follow-up ($\text{mean}=8.4y$), 2,225 invasive and 623 ductal carcinoma in situ (DCIS) cases were identified. ${\mathrm{PM}}_{2.5}$ and ${\mathrm{NO}}_2$ were associated with breast cancer overall [$\text{HR}=1.05$ (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 ${\mathrm{PM}}_{2.5}$ only in the Western United States [$\text{HR}=1.14$ (95% CI:1.02, 1.27)] and ${\mathrm{NO}}_2$ only in the Southern United States [$\text{HR}=1.16$ (95% CI:1.01, 1.33)]. ${\mathrm{PM}}_{2.5}$ was associated with a higher risk of invasive breast cancer among two of seven identified composition-based clusters. A higher risk was observed [$\text{HR}=1.25$ (95% CI: 0.97, 1.60)] in a California-based cluster characterized by low S and high Na and nitrate (${\mathrm{NO}}_3^{-}$) fractions and for another Western United States cluster [$\text{HR}=1.60$ (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. https://doi.org/10.1289/EHP5131.

Figure 1.

Predicted ${\mathrm{PM}}_{2.5}$ component cluster membership by geographic region (jittered to protect confidentiality), Sister Study, 2003–2009. Figure adapted from Keller et al. (2017). ${\mathrm{PM}}_{2.5}$, particulate matter $<2.5\mathrm{\mu }\mathrm{m}$ in aerodynamic diameter.

Figure 2.

Relative composition by ${\mathrm{PM}}_{2.5}$ clusters. Clusters were identified using predictive k-means in the 2010 annual average ${\mathrm{PM}}_{2.5}$ component data. Species mass fractions were log transformed and then standardized. EC, elemental carbon; NO3, nitrate; OC, organic carbon; ${\mathrm{PM}}_{2.5}$, particulate matter $<2.5\mathrm{\mu }\mathrm{m}$ in aerodynamic diameter; SO4, sulfate.