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Science. 2015 Jan 2;347(6217):81-3. doi: 10.1126/science.1262092. Epub 2014 Dec 4.

Mutagenesis. Smoking is associated with mosaic loss of chromosome Y.

Author information

  • 1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Science for Life Laboratory, Uppsala University, Uppsala, Sweden. jan.dumanski@igp.uu.se lars.forsberg@igp.uu.se.
  • 2Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • 3Södertörn University, School of Life Sciences, Biology, Huddinge, Sweden.
  • 4Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
  • 5Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • 6Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
  • 7Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Department of Biostatistics, University of Liverpool, Liverpool, UK.
  • 8Center for Experimental Social Science, New York University, New York, NY 10012, USA.
  • 9Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
  • 10Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • 11Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Abstract

Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared with females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% confidence interval (CI) = 2.8 to 6.7; Uppsala Longitudinal Study of Adult Men: OR = 2.4, 95% CI = 1.6 to 3.6; and Prospective Investigation of the Vasculature in Uppsala Seniors: OR = 3.5, 95% CI = 1.4 to 8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.

PMID:
25477213
PMCID:
PMC4356728
DOI:
10.1126/science.1262092
[PubMed - indexed for MEDLINE]
Free PMC Article
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