Y Chromosome Loss Linked to Higher Cancer Risk in Men
MONDAY, April 28, 2014 -- As men age, the Y chromosome can start to disappear from some of their body cells -- something scientists have seen as normal. But a new study suggests that "loss of Y" might signal an increased risk of cancer.
Researchers found that of more than 1,100 elderly men, those who showed a significant depletion of the Y chromosome in their blood cells died about five years earlier. They also had over three times the risk of dying from cancer.
The findings, published online April 28 in Nature Genetics, don't prove that Y chromosome loss causes cancer. But researchers said it might serve as a "marker" (or indicator) of an increased cancer risk and help explain the higher incidence of nonsex-related cancer in older men than in women.
Men have an X and a Y chromosome, while women have two X chromosomes. And experts used to think that the Y -- short and stumpy compared with the X -- did little more than determine male sex and ensure normal sperm production.
But recent studies have shown that the Y chromosome actually contains a large number of genes, whose jobs are not fully understood yet. Researchers have also found that the chromosome is sometimes absent in human cancer cells.
"Loss of Y has previously been considered a part of normal aging," said Lars Forsberg, a researcher at Uppsala University in Sweden who led the new study.
But based on his team's findings, that might not be the case. Forsberg said the findings raise the possibility that blood tests looking for loss of Y could help predict men's cancer risk.
A researcher who reviewed the study said it was "very interesting."
"We used to think most of the Y chromosome was junk," said Dr. Martin Bialer, a medical geneticist with North Shore-LIJ Health System in Great Neck, N.Y.
"But this study suggests there could be something on the chromosome that's important in cancer prevention," Bialer said. "What that is, is unclear."
The study shows only an association between Y chromosome loss and cancer, not a cause-and-effect relationship. But, Bialer said, the researchers accounted for some other factors that might have explained the connection, including older age, smoking, excess weight, diabetes and high blood pressure.
Even then, Y chromosome loss itself was linked to shorter survival and a higher cancer risk.
The findings are based on 1,153 Swedish men who were part of a long-term health study. Forsberg's team analyzed DNA from blood samples the men gave when they were in their 70s and early 80s.
Overall, at least 8 percent of the men had a loss of Y in their blood cells, the researchers found. And around 2 percent had no Y chromosome in at least 35 percent of their blood cells. Those men typically died 5.5 years sooner than other men, and were over three times more likely to die of cancer.
"One of the most important aspects of our results is that loss of Y in cells in a single sample of blood can predict cancer in the other organs of the body," Forsberg said.
He speculated that without the Y chromosome, immune system cells may function less well, potentially allowing cancer to grow and spread. But that's still under study.
The other big question is whether a Y chromosome blood test could really help gauge an older man's cancer risk.
Although similar results were found in a group of slightly younger men, more studies should be done in different populations, to confirm that the association is consistent, Bialer said. If it is, that would still leave a larger issue: Is testing older men for Y chromosome loss worthwhile?
"Clinicians will have to determine whether testing is even useful," Bialer said. "If a test shows that a man has an increased cancer risk, would there be anything you can do about it?"
Men are not the only ones who lose their sex chromosomes as they age. Women, too, can lose X chromosomes from their cells, Bialer noted.
Forsberg said he expects that "similar biomarkers" for disease risk will be found for women.
The U.S. National Library of Medicine has more on the Y chromosome.
Posted: April 2014
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