Cigarette Smoking Associated With Loss of Y Chromosome

Cigarette Smoking Associated With Loss of Y Chromosome

One of the most commonly acquired human mutations is the loss of chromosome Y (LOY) in blood cells. Blood cell LOY is associated with an increased risk for nonhematologic tumors. A new study suggests that smoking induces LOY and is thus a preventable risk factor for this common human mutation.

Jan P. Dumanski, PhD, from Uppsala University in Sweden, and colleagues published the results of their research online December 4 in Science.

The study was designed to determine possible causes of LOY. The researchers evaluated three separate cohorts (a total of 6014 men) for their analysis: TwinGene, the Uppsala Longitudinal Study of Adult Men, and the Prospective Investigation of the Vasculature in Uppsala Seniors.

LOY was the most common postzygotic mutation identified in the three cohorts. The investigators found that men who smoked were three times more likely to lose their Y chromosomes than nonsmokers. Moreover, LOY was more common in current smokers than in nonsmokers.

The only factor other than smoking that was associated with LOY was age.

The association between smoking and LOY appeared to exist only in current smokers. Thus, smoking appears to have a transient mutagenic effect on LOY status.

“Our results are consistent with a previously described dynamic nature of expanding-contracting noncancerous cell clones in blood affected with mosaic genetic aberrations; i.e., it appears that the relative frequency of cells from a cell clone can first increase and then decrease later in life. In the present analyses, LOY was detected in ≥10% of blood cells from about 15% of elderly males in three cohorts,” the authors write.

Tobacco smoking is estimated to have killed approximately 100 million people during the twentieth century and is a known risk factor for cancers outside of the respiratory tract. Epidemiologic data suggest that smoking represents a greater cancer risk for men than for women. Men also have a higher incidence of and mortality from most cancers that are not sex-specific.

The investigators note that the study was not designed to determine whether smoking-induced LOY plays a direct role in cancer.

Dr Dumanski is a cofounder and shareholder in Cray Innovatio AB as well as coowner of a patent protecting the commercial applications of LOY for the assessment of cancer risk.