Format

Send to

Choose Destination
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

1
Department 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.
2
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
3
Södertörn University, School of Life Sciences, Biology, Huddinge, Sweden.
4
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
6
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
7
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Department of Biostatistics, University of Liverpool, Liverpool, UK.
8
Center for Experimental Social Science, New York University, New York, NY 10012, USA.
9
Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
10
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
11
Science 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
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center