title: Mutagenesis. Smoking is associated with mosaic loss of chromosome Y.
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.
authors.affiliation: 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.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rasi
authors.affiliation: Södertörn University, School of Life Sciences, Biology, Huddinge, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lönn
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Davies
authors.affiliation: Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.affiliation: Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Vilmantas
authors.initials: V
authors.lastname: Giedraitis
authors.affiliation: Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: Center for Experimental Social Science, New York University, New York, NY 10012, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cesarini
authors.affiliation: Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Johannesson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Tiensuu Janson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: 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.
authors.forename: Lars A
authors.initials: LA
authors.lastname: Forsberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000378:metabolism; D041322:Chromosomes, Human, Y / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D013548:Sweden