Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study

Background: Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear. Objective: We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY. Methods: We analyzed baseline (1989-1993) blood samples from 933 men >= 65 years of age from the prospective Cardiovascular Health Study. Particulate matter <= 10 mu m (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants' monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR. Results: Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend= 0.03). Compared with the lowest tertile (<= 28.5 mu g/m(3)), the middle (28.5-31.0 mu g/m(3); beta=-0.0044, p= 0.09) and highest (>= 31 mu g/m(3); beta=-0.0054, p= 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (beta=-0.00035, p= 0.06) and smoking pack-years (beta=-0.00011, p= 1.4E-3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants. Conclusions: PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.