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 more likely to die of them when they do.
Researchers have found that smokers are up to four times more likely to have blood cells with no Y chromosome than nonsmokers. A recent study found an association between Y chromosome loss and a shorter life span, as well as a higher risk of multiple cancers.
Fosberg and Dumanski found that the loss of Y chromosomes from blood cells occurred in 8.2% of elderly men in a sample of 1153 and that those affected had life expectancies 5.5% shorter and three and half times the rate of cancer, after excluding haematological cancers.
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 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.
Meanwhile, there is some reassuring news for smokers, Forsberg says. Y chromosome damage caused by smoking appears to be reversible and dose-dependent. Previous smokers were no more likely to have Y chromosome loss than those who have never smoked, he notes, so it’s never too late to quit.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.