Smoking is associated with mosaic loss of chromosome Y

Jan P. Dumanski, Chiara Rasi, Mikael Lönn, Hanna Davies, Martin Ingelsson, Vilmantas Giedraitis, Lars Lannfelt, Patrik K.E. Magnusson, Cecilia M. Lindgren, Andrew P. Morris, David Cesarini, Magnus Johannesson, Eva Tiensuu Janson, Lars Lind, Nancy L. Pedersen, Erik Ingelsson, Lars A. Forsberg

    Research output: Contribution to journalArticlepeer-review

    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.

    Original languageEnglish (US)
    Pages (from-to)81-83
    Number of pages3
    JournalScience
    Volume347
    Issue number6217
    DOIs
    StatePublished - Jan 2 2015

    ASJC Scopus subject areas

    • General

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