Smoking Can Erase Y ‘Masculinity’ Chromosome From Cells

Public health authorities have been handed their next anti-smoking campaign on a plate, at least when targeting men, with the discovery that smoking wipes out the chromosomes that determine genetic masculinity.

Earlier this year, a team led by Lars Fosberg and Jan P. Dumanski of Uppsala University tackled the question of why men develop more cancers that are not related to reproductive organs, and are more likely to die of them when they do.

The authors note that “Age-related loss of chromosome Y is frequent in normal hematopoietic cells,” but that the consequences of this remain poorly understood.

Fosberg and Dumanski found that the loss of Y chromosomes from blood cells occurred in 8.2% of elderly men in a sample of 1,153 and that those affected had life expectancies 5.5% shorter and three and half times the rate of cancer, after excluding haematological cancers.

As the authors point out, “These … could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination.”

This naturally led to the question of what causes the body to lose Y chromosomes, and the same team have now followed up with a paper in Science demonstrating that tobacco smoking is one of the main answers.

While they tested for exercise, diabetes, Body Mass Index, education and alcohol intake, only smoking (and in one case age) significantly increased Y chromosome loss in three separate cohorts aged 48-93. The authors note this was “by far the most common post-zygotic mutation found,” occurring in 12-16% of the samples aged 70 and over. Loss was 2.4-4.3 times as likely for smokers and non smokers.

The effect increases the more one smokes. The one piece of good news is that the effects greatly reduce, or even stop, when smoking ceases, suggesting “a dynamic and reversible process.” This is in keeping with studies that find, “For smokers who quit at 25 to 34 years of age, survival was nearly identical with those who had never smoked.”

All this goes some way to explaining the previously mysterious observation that, in the paper’s words, “Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females.”

The authors admit they do not know whether the disappearance of Y chromosomes is a cancer risk in itself, or simply an incidental factor for other genetic damage. Nevertheless, one test showed the loss was most severe in cells that have a role in the immune system, a finding the authors consider consistent with the idea that Y chromosomes have some ongoing role in fighting tumors.

The authors have founded a startup to provide a blood test for Y chromosome loss to offer a warning of cancer risk for older men.

All those ads associating cigarettes with stereotypically masculine activities like herding cattle look particularly desperate in hindsight.