26 May, 2024
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Male chromosome loss linked to life-threatening cancers and early death


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Two mysteries. More men develop colo-rectal cancer than women, and more of them die. Meanwhile, more men develop aggressive bladder cancer.


Well… ‘Y’ indeed.

Two new studies found that the Y chromosome – the thing that makes a person biologically male – is to blame.

As you’ll remember from school, biological women have two X chromosomes, and men have an X and Y chromosome.

As men age…

This may sound strange, but at least 40 percent of males lose the Y chromosome from some of their blood cells by age of 70. This loss occurs during cell division.

The rate of this loss increases with age: at least 57 percent of men aged 93 have lost some of their Y chromosomes.

This has been known for more than 50 years and for most of that time it was deemed a matter of no consequence.

Hair, teeth, cartilage, erections and mental sharpness tend to fall out or fall apart as men age.

The sporadic loss of the Y chromosome was seen as just one more thing.

That began to change

In 2017, an article in Human Genetics pointed to accumulating evidence that suggested men who have lost their Y chromosomes are prone to a range of diseases associated with ageing.

Specifically, “harbouring cells without the Y chromosome in the peripheral blood was associated with increased risk for all-cause mortality and disease such as different forms of cancer (and) Alzheimer’s disease.

The point of the article was to offer a potential explanation as to why men, in the main, lived shorter lives than women.

Last year, US and Japanese researchers, in a mouse model study,  found that loss of the Y chromosome seemed to cause scar tissue in the heart, heart failure and death.

These researchers also cited studies that had shown an increase in risk for heart disease and cancer in men who had lost the Y chromosome.

Bladder cancer joins the missing Y club

New research from Cedars-Sinai Cancer, published in the journal Nature, found that “loss of the Y chromosome helps cancer cells evade the body’s immune system”.

Dr Dan Theodorescu, director of Cedars-Sinai Cancer.

Specifically, found that this Y chromosome loss “results in aggressive bladder cancer, but somehow also renders the disease more vulnerable –  and responsive – to a standard treatment called immune checkpoint inhibitors”.

“This study for the first time makes a connection that has never been made before between loss of the Y chromosome and the immune system’s response to cancer,” said Dr Dan Theodorescu, director of Cedars-Sinai Cancer, and the corresponding author of the paper.

“We discovered that loss of the Y chromosome allows bladder cancer cells to elude the immune system and grow very aggressively.”

The authors note that loss of the Y chromosome “is observed in multiple cancer types, including 10–40 per cent of bladder cancers, but its clinical and biological significance is unknown”.

Until now. To read more about the research, see here.

Colorectal cancer

Even when the Y chromosome isn’t missing it sometimes causes serious trouble.

A mouse study of colorectal cancer found that a gene on the Y chromosome “raises the risk of some colorectal cancers spreading to other parts of the body”.

The researchers, from the University of Texas, found that the gene, called KDM5D, not only drives metastasis (spreading of the cancer) but also inhibits anti-tumor immunity.

The researchers found that KDM5D appears to “weaken connections between tumour cells, helping the cells to break away and spread to other parts of the body”.

Obviously, again, this mechanism occurs only in men.

An article in Nature reports: “When that gene was deleted, tumour cells became less invasive.” They were also more likely to be recognized by immune cells.”

This presents “a potential target for anti-cancer therapies”, said co-author Ronald DePinho. “This is a druggable target.”

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