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Smoking is associated with mosaic loss of chromosome Y

Science  02 Jan 2015:
Vol. 347, Issue 6217, pp. 81-83
DOI: 10.1126/science.1262092

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Men beware, when smoke gets in your Y's

The relationship between tobacco smoking and elevated cancer risk has been recognized for 60 years. Yet what smoking does to our genetic material is still not fully understood. New work suggests that men should be particularly concerned. In a study of over 6000 men, Dumanski et al. find that men who smoke are more than three times as likely as nonsmokers to show loss of the Y chromosome in their blood cells. Whether this is a causal factor in cancer development or simply a marker of more consequential damage on other chromosomes could not be deduced from the study.

Science, this issue p. 81

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.

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