Men who lose Y chromosome have high risk of cancer

Genetic defect in blood cells also associated with shorter life span

illustration of X and Y chromosomes

SMALL BUT MIGHTY  The Y chromosome (blue in an illustration) is far smaller than the X chromosome (green) and contains few genes, but its loss may spell big trouble for men. Men whose blood cells have jettisoned the chromosome have a higher risk of cancer and may have shorter life spans.


SAN DIEGO — Losing the Y chromosome in blood cells may bring on cancer and shorten men’s lives, new research suggests. By age 70, about 15 percent of men have lost the Y chromosome from a proportion of their blood cells, statistician and bioinformaticist Lars Forsberg of Uppsala University in Sweden reported October 21 at the annual meeting of the American Society of Human Genetics.

Forsberg and his colleagues made the discovery by examining the DNA of more than 6,000 Swedish men.

In June, Forsberg’s team reported linking Y chromosome loss to a higher risk of several types of cancer and a decreased life span in a smaller group of men. Men in whom at least 10 percent of blood cells lack the Y chromosome have an average life expectancy of 5.5 years, while men who keep their Ys live around twice as long. The older a man gets, the more of his blood cells lack a Y chromosome, the researchers found.

The Y chromosome loss may weaken immune cells, including white blood cells, making it harder to fight off cancer, Forsberg said.

The researchers think that Y loss may start sometime around age 40 but doesn’t become detectable until 5 to 10 percent of blood cells are missing the chromosome. Y chromosomes are probably lost when cells divide, with some cells failing to divvy up their chromosomes equally. The team is still investigating what might trigger the process in middle age.

A separate study of more than 8,700 men with cancer and more than 5,300 healthy men also found that Y chromosome loss increases with age. About 19 percent of men in the study were missing the chromosome in blood cells by age 80, Stephen Chanock of the National Cancer Institute in Rockville, Md., and colleagues reported October 19 at the conference. Smoking may get Y chromosome loss started, the researchers found.

Although Chanock’s group found no association with shorter life span, the researchers did find a link between missing Y chromosomes and certain types of cancer.

“They’ve discovered a correlation that replicates, so it’s probably not a fluke,” said Michael Province, a statistical geneticist at Washington University in St. Louis, noting that two research teams independently discovered the correlation in different groups of men.

But that doesn’t necessarily mean that losing the Y chromosome causes cancer, he stressed. “We just know that they’re cohappening.” Different types of studies are needed to find the true nature of the relationship between Y chromosome loss and cancer, Province said.

Even if losing the Y doesn’t directly cause cancer, the event might signal that a man is at risk, Forsberg said. Men missing Y chromosomes should probably receive more frequent cancer screening, he suggested.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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