Air pollution and breast cancer: an examination of modification by familial breast cancer risk

Abstract

BACKGROUND AND AIM: Women with a breast cancer family history may differ in their susceptibility to carcinogenic effects of environmental exposures. We evaluated whether associations between air pollution and breast cancer varied by underlying breast cancer risk predicted by a family history-based score among a population enriched with high-risk women. METHODS: We included 48,453 Sister Study participants living in the contiguous US who were ages 35-74 at enrollment (2003-2009) and were followed-up for breast cancer through September 2019. Annual PM10, PM2.5, and NO2 concentrations at enrollment residences were estimated using a regionalized universal kriging model. We predicted each woman’s 1-year risk of breast cancer using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a pedigree-based model incorporating cancer information on first- and second-degree relatives. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression. Associations between each pollutant and breast cancer were stratified by BOADICEA ( vs. ≤ median ( 0.46%)) and modification was examined using an air pollution-by-BOADICEA interaction term. Given the regional heterogeneity of air pollution, we also evaluated differences across US regions. RESULTS:BOADICEA did not significantly modify the associations between the air pollutants and breast cancer. However, PM2.5 was associated with a higher breast cancer risk among women median BOADICEA (PM2.5 quartile 4 vs. 1: HR=1.12; 95% CI: 0.99-1.26), but not ≤ median (HR=0.95; 95% CI: 0.82-1.10) (p-heterogeneity=0.3). This was particularly evident in the Southern US: PM2.5 quartile 4 vs. HR=1.41 (95% CI: 1.10-1.80) among those median and HR=0.89 (95% CI: 0.66-1.20) among those ≤ median BOADICEA (p-heterogeneity=0.1). CONCLUSIONS:We did not find strong evidence that women at greater underlying breast cancer risk are more susceptible to air pollution. Suggestive associations for PM2.5 among women at greater underlying risk who reside in the Southern US may warrant further investigation. KEYWORDS: Air pollution, particulate matter, cancer and cancer precursors