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 publication




Journal article


Science (New York, N.Y.)

Publication Date





81 - 83


Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.


Blood Cells, Chromosomes, Human, Y, Humans, Lung Neoplasms, Incidence, Risk Factors, Cohort Studies, Smoking, Sex Factors, Mutagenesis, Aged, Aged, 80 and over, Middle Aged, Sweden, Female, Male