Smoking is associated with mosaic loss of chromosome Y

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 to females. This observation, together with the fact that males have a higher incidence of, and mortality from, most non-sex-specific cancers, remain unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of non-hematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts (TwinGene: odds ratio [OR]=4.3, 95% CI =2.8-6.7; ULSAM: OR=2.4, 95% CI=1.6-3.6; and PIVUS: OR=3.5, 95% CI=1.4-8.4) 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.

Sexual dimorphism in cancer

“…Importantly, Y chromosome loss occurs also in normal tissues; it is frequently observed in normal hematopoietic cells of elderly men and is significantly associated with a greater risk of cancer 140,141 . Y chromosome loss in blood cells could be used as predictive biomarker and is also induced by smoking 141 .…”

“…Y chromosome loss in blood cells could be used as predictive biomarker and is also induced by smoking 141 . However, it remains to be determined whether or not widespread loss of Y chromosomal regions promotes cancer development or simply results from elimination of unnecessary genetic material, as proposed during evolution 142 .…”

Chromosome aberrations frequency in peripheral blood lymphocytes in young tobacco smoking and non-smoking people

“…Shi et al confirmed that the frequency of disomy 13 in sperm cells was significantly higher in light and heavy smokers than in non-smokers (33). In addition, loss of chromosome Y in blood cells is associated with both cigarette smoking and increased risk of nonhematological tumors (34).…”

Systems Epigenomics and Applications to Ageing and Cancer

“…However, predicting the risk of a given cancer requires, in principle, access to a relevant tissue, the most relevant one being the normal cell of origin that gives rise to the cancer. In the case of blood-borne cancers, this is, in principle, feasible, and indeed recent studies indicate that prospective risk prediction of haematological cancers may be possible (Anjum et al 2014;Dumanski et al 2015;Forsberg et al 2014;Genovese et al 2014;Jacobs et al 2012;Laurie et al 2012;Xie et al 2014;Xu et al 2013). However, the case of epithelial cancers is far more challenging given that the normal cell of origin is usually not readily accessible.…”

“…The emphasis in cancer genomics is slowly shifting from prognosis and treatment to early detection and risk prediction (Anjum et al 2014;Dumanski et al 2015;Forsberg et al 2014;Genovese et al 2014;Jacobs et al 2012;Laurie et al 2012;Xie et al 2014;Xu et al 2013). This shift is happening for various reasons.…”