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

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Dumanski, Jan P; Rasi, Chiara; Lönn, Mikael; Davies, Hanna; Ingelsson, Martin; Giedraitis, Vilmantas; Lannfelt, Lars; Magnusson, Patrik K E; Lindgren, Cecilia M; Morris, Andrew P; Cesarini, David; Johannesson, Magnus; Tiensuu Janson, Eva; Lind, Lars; Pedersen, Nancy L; Ingelsson, Erik; Forsberg, Lars A
Year of Publication: 2015
Journal: Science
Volume: 347
Issue: 6217
Pagination: 81-3
Date Published: 2015 Jan 2
Publication Language: eng
ISSN: 1095-9203
Keywords: Aged, Aged, 80 and over, Blood Cells, Chromosomes, Human, Y, Cohort Studies, Female, Humans, Incidence, Lung Neoplasms, Male, Middle Aged, Mutagenesis, Risk Factors, Sex Factors, Smoking, Sweden

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.

DOI: 10.1126/science.1262092
Alternate Journal: Science