02793nas a2200289 4500008004100000022001400041245010900055210006900164260001600233300001200249490000800261520193000269100002002199700002402219700002302243700001702266700002302283700002002306700001802326700001902344700002202363700002402385700002302409700001402432700002102446856003602467 2018 eng d a1873-675000aOutdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study.0 aOutdoor air pollution and mosaic loss of chromosome Y in older m c2018 Apr 23 a239-2470 v1163 a

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 μm (PM), 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 PM was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m), the middle (28.5-31.0 μg/m; β = -0.0044, p = 0.09) and highest (≥31 μg/m; β = -0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = -0.00035, p = 0.06) and smoking pack-years (β = -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: PM may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

1 aY Y Wong, Jason1 aMargolis, Helene, G1 aMachiela, Mitchell1 aZhou, Weiyin1 aOdden, Michelle, C1 aPsaty, Bruce, M1 aRobbins, John1 aJones, Rena, R1 aRotter, Jerome, I1 aChanock, Stephen, J1 aRothman, Nathaniel1 aLan, Qing1 aLee, Jennifer, S uhttps://chs-nhlbi.org/node/7663