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

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Electronic address: jason.wong@nih.gov.
² Department of Internal Medicine, School of Medicine, University of California, Davis, CA, USA.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
⁴ Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Leidos Biomedical Research Inc., Bethesda, MD, USA.
⁵ School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.
⁶ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
⁷ Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸ Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, and Division of Epidemiology, Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA, USA; Medical Services, Veteran Affairs, Palo Alto, Health Care System, CA, USA.

PMID: 29698900
PMCID: PMC5971001
DOI: 10.1016/j.envint.2018.04.030

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

Jason Y Y Wong et al. Environ Int. 2018 Jul.

. 2018 Jul:116:239-247.

doi: 10.1016/j.envint.2018.04.030. Epub 2018 Apr 24.

Authors

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Electronic address: jason.wong@nih.gov.
² Department of Internal Medicine, School of Medicine, University of California, Davis, CA, USA.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
⁴ Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Leidos Biomedical Research Inc., Bethesda, MD, USA.
⁵ School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.
⁶ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
⁷ Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸ Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, and Division of Epidemiology, Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA, USA; Medical Services, Veteran Affairs, Palo Alto, Health Care System, CA, USA.

PMID: 29698900
PMCID: PMC5971001
DOI: 10.1016/j.envint.2018.04.030

Abstract

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 (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 μg/m³), the middle (28.5-31.0 μg/m³; β = -0.0044, p = 0.09) and highest (≥31 μg/m³; 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: PM₁₀ may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

Keywords: Air pollution; Genetic mosaicism; Genomic instability; Loss of chromosome Y; PM(10).

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Conflict of interest statement

Competing financial interests

None of the other authors declares any actual or potential competing financial interests.

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

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

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Conflict of interest statement

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