"Long before it's in the papers"
January 27, 2015


Men’s “Y chromosome” may be a vulnerability

Dec. 4, 2014
Courtesy of Uppsala University
and World Science staff

New re­search sug­gests the Y chro­mo­some—a re­pos­i­tory of genes that only males have—may help ex­plain why men live less long than wom­en, and are more sus­cep­ti­ble to smok­ing-related can­cers.

With ad­vanc­ing age, some cells can lose their Y chro­mo­some. Two new studies sug­gest this loss may in­crease can­cer risk—and that smok­ing may ex­ac­er­bate the chro­mo­some loss. Both pro­jects came from the same group of re­search­ers, and while they did not prove cause-and-ef­fect rela­t­ion­ships, they found as­socia­t­ions be­tween the events in ques­tion.

The ear­li­er stu­dy, pub­lished in the re­search jour­nal Na­ture Ge­net­ics on­line April 28, “demon­strated an as­socia­t­ion be­tween loss of the Y chro­mo­some in blood and great­er risk for can­cer,” said Lars Fors­berg of Upp­sa­la Uni­vers­ity in Swe­den, one of the in­ves­ti­ga­tors.

For the sec­ond proj­ect, pub­lished in the Dec. 4 is­sue of the re­search jour­nal Sci­ence, he added that the group tested “if there were any lifestyle- or clin­i­cal fac­tors that could be linked to loss of the Y chro­mo­some.”

The re­sult: “Out of a large num­ber of fac­tors that were stud­ied, such as age, blood pres­sure, di­a­be­tes, al­co­hol in­take and smok­ing, we found that loss of the Y chro­mo­some in a frac­tion of the blood cells was more com­mon in smok­ers than in non-smok­ers.”

Y chro­mo­some loss is “the most com­mon hu­man muta­t­ion” to beg­in with, added Jan Du­man­ski, a co-re­searcher at Upp­sa­la. The new work “may in part ex­plain why men in gen­er­al have a shorter life span than wom­en, and why smok­ing is more dan­ger­ous for men.”

Smok­ing is a risk fac­tor for var­i­ous dis­eases, not only lung can­cer, the re­search­ers not­ed; male smok­ers have shown a great­er risk of de­vel­op­ing non-respiratory-tract can­cers than female smok­ers.

The in­ves­ti­ga­tors found the as­socia­t­ion be­tween smok­ing and Y chro­mo­some loss to be “dose de­pen­den­t”—heavy smok­ers had more wide­spread losses. But ex-smok­ers who had quit showed nor­mal lev­els of Y chro­mo­some loss. So “this pro­cess might be re­versible,” which “could be very per­sua­sive for mo­ti­vat­ing smok­ers to quit,” said Fors­berg.

How the smok­ing-induced Y chro­mo­some loss in blood cells is linked to can­cer re­mains un­clear. Per­haps im­mune cells in blood, be­reft of Y chro­mo­somes, are less able to fight can­cer cells, the sci­en­tists spec­u­lat­ed.

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New research suggests the Y chromosome—a repository of genes that only males have—may help explain why men live less long than women and are more susceptible to smoking-related cancers. Two new studies focus on a common occurrence in which with advancing age, some cells lose their Y chromosome. The research suggests this loss may increase cancer risk, and that smoking may exacerbate the Y chromosome loss. Both projects came from the same group of researchers, and while they did not prove cause-and-effect relationships, they found associations between the events in question. The earlier study, published in the research journal Nature Genetics online April 28, “demonstrated an association between loss of the Y chromosome in blood and greater risk for cancer,” said Lars Forsberg of Uppsala University in Sweden, one of the investigators. For the second project, published in the Dec. 4 issue of the research journal Science, he added that the group tested “if there were any lifestyle- or clinical factors that could be linked to loss of the Y chromosome.” The result: “Out of a large number of factors that were studied, such as age, blood pressure, diabetes, alcohol intake and smoking, we found that loss of the Y chromosome in a fraction of the blood cells was more common in smokers than in non-smokers.” Y chromosome loss is “the most common human mutation” to begin with, added Jan Dumanski, a co-researcher at Uppsala. The new work “may in part explain why men in general have a shorter life span than women, and why smoking is more dangerous for men.” Smoking is a risk factor for various diseases, not only lung cancer, the researchers noted; male smokers have shown a greater risk of developing non-respiratory-tract cancers than female smokers. The investigators found the association between smoking and Y chromosome loss to be “dose dependent”—heavier smokers had more widespread losses. But ex-smokers who had quit showed normal levels of Y chromosome loss. So “this process might be reversible,” which “could be very persuasive for motivating smokers to quit,” said Forsberg. How the smoking-induced Y chromosome loss in blood cells is linked to cancer remains unclear. Perhaps immune cells in blood, bereft of Y chromosomes, are less able to fight cancer cells, the scientists speculated.