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

DOI

10.1126/science.1262092

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

01/2015

Volume

347

Pages

81 - 83

Addresses

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.

Keywords

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