Journal
SCIENCE
Volume 347, Issue 6217, Pages 81-83Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1262092
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Funding
- Swedish Cancer Society
- Swedish Research Council [M-2005-1112]
- Swedish Heart-Lung Foundation and Science for Life Laboratory Uppsala
- Olle Enqvist Byggmastare Foundation
- Wellcome Trust [WT098017, WT064890, WT090532]
- Uppsala University
- Uppsala University Hospital
- Swedish Heart-Lung Foundation
- GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254]
- NIH DK [U01-066134]
- Swedish Foundation for Strategic Research (SSF)
- Heart and Lung foundation [20070481]
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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.
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