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Men Who Smoke Lose Their Y Chromosomes

by Lulu Chang

In case you needed yet another reason not to smoke, scientists from Sweden's Uppsala University have found that men who smoke lose their Y chromosomes in their blood cells, which may explain why male smokers are at a higher risk of contracting cancer than their female counterparts. In the recent study published in Science , researchers discovered a link between smoking and the loss of Y chromosomes (men's sex is determined by the presence of one X and one Y chromosome, whereas women have two X chromosomes). While the disappearance of Y chromosomes has long been observed in older men, recent medical research has suggested that the loss of the chromosome is closely associated with shorter life spans and cancer.

Study co-author Lars Forsberg spoke of the troubling discovery with LiveScience, saying "The cells that lose the Y chromosome…They don't die. But we think that they would have a disrupted biological function." And the particular biological function they disrupt is that which fights cancer. Simply put, "Male smokers are at greater risk 'for loss of Y.' It’s the most common human mutation, and it’s associated with cancer." While it is unclear whether the loss of the chromosome contributes separately to the other carcinogenic factors associated with smoking, it should be noted that cigarettes have yet another potentially dangerous side effect.

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The study examined 6,000 men who were also participating in other health-related studies. This allowed Forsberg and his colleagues to monitor their participants' habits and other factors, including their age, blood pressure, diabetes and alcohol intake. When they examined the men who were missing Y chromosomes from their blood cells, they found that the only consistent factor amongst these individuals, other than age, was smoking. The more a man smoked, the fewer Y chromosomes he had, scientists said. In fact, across the board, smokers were between 2.4 and 4.3 more likely to lose Y chromosomes when compared with nonsmokers of the same age.

Interestingly enough, the effects of smoking on Y chromosomes appears to be reversible, as researchers also noted that men who stopped smoking had nearly identical levels of Y chromosomes floating around in their blood stream as men who had never smoked a day in their lives. "When you stop smoking," Forsberg said, "These cell clones with loss of [the] Y [chromosome] will disappear from circulation," so the damage is far from permanent, at least in terms of this particular side effect.

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The loss of the Y chromosome, despite its role as a sex determinant, has nothing to do with "manliness" or other supposedly masculine traits among men. As Forsberg pointed out, "The Y chromosome is involved in much more than sex determination and reproduction," and scientists believe that Y chromosomes may contain some of the genetic code that is needed to fight off cancer and other ailments. Male smokers not only have a higher risk of lung cancer than female smokers, but also are more likely to suffer from other types of cancer as well.

Despite these new discoveries, significant research is still needed to determine what about smoking causes Y chromosomes to disappear, and more importantly, what the role of Y chromosomes is in the immune system. This may shed much-needed light on the question of why the loss of Y chromosomes is linked to cancer and shorter life spans in general.

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Daniel Bellot, a geneticist at MIT unaffiliated with the study, told The Verge that the results of the study were exciting and potentially groundbreaking — if nothing else, "it provides more evidence that smoking can cause cancer by a second mechanism," not just the chemicals in smoke. If entire chromosomes can be affected, or in this case, completely lost as a result of smoking, "dozens to thousands of genes would be affected at once," which is "pretty scary," according to Bellot.

If the loss of Y chromosomes is ultimately determined to be an early marker of cancer, this could provide new screening methods for the disease. Already, a startup called CRAY Innovation (Cancer Risk Assessment from loss of chromosome Y Innovation), has been developed with the purpose of creating a "diagnostic test that could assess a man’s risk of cancer based on loss of chromosome Y in blood cells."

Forsberg and his co-author Jan Dumanski both recognize that considerably more research is needed in order to fully understand the effects of smoking on the male genome, but this presents an intriguing starting point that may provide new insights into cancer prevention, particularly among smokers. And regardless of any additional research, Forsberg noted that these preliminary findings should "be very persuasive for motivating smokers to quit." Said Forsberg, "If you want to stay healthy and alive, quit smoking today."

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