Loss of Y chromosome in men promotes cancer growth, new study finds

“If it is missing we can say that these patients will be more likely to respond to “immune checkpoint inhibitors” treatment,” he added.

Connections between the Y chromosome and cancer 

Men have XY as sex chromosomes, and women have XX. So when the researchers say men lose Y chromosomes with age, they don’t mean men lose all their sex chromosomes. This age-related loss of the Y chromosome is only limited to some body cells.

However, previous studies hint that this change has some profound implications. For instance, about 10 to 40 percent of bladder cancer cases are reported in men who suffer the loss of Y chromosomes in their white blood cells, according to the researchers. 

This loss is also associated with a higher risk of cancer, heart ailments, and neurological disease. Still, until now, nobody could explain how the Y chromosome affects our body’s immune response. 

The study authors realized that the Y chromosome regulates the expression of specific genes in many body cells, including those which make up the bladder. 

So they analyzed the data of bladder cancer patients and performed some experiments to find links between the Y chromosome and cancer immunity. They found that those patients who lost Y chromosomes and went through immune checkpoint inhibitor treatment had better survival rates than those who didn’t receive the treatment and instead had their bladders removed.

"Fortunately, this aggressive cancer has an Achilles’ heel, in that it is more sensitive than cancers with an intact Y chromosome to immune checkpoint inhibitors,” said Hany Abdel-Hafiz, study co-author and an associate professor at Cedars-Sinai.

To investigate their findings further, they cultured bladder cancer cells in a dish and, at the same time, checked the growth of bladder cancer in mouse models. The dish and the mice lacked immunity cells, but unlike the culture, mice had Y chromosomes in their body cells. 

The researchers noticed that cancer tumors increased at the same rate in the dish (no Y chromosome) and mice (Y chromosome present). They further studied the growth of the disease in another mice group having immune cells.  

Surprisingly, cancer was found to be growing at a faster rate in mice whose tumor cells lacked the Y chromosome. “These results imply that when cells lose the Y chromosome, they exhaust T-cells. And without T-cells to fight cancer, the tumor grows aggressively,” said Theodorescu.

Can men recover their lost Y chromosomes?

The main limitation of the current study is that it has shown the connection only about bladder cancer. There is a great possibility that Y chromosome loss is also linked to other cancer types.

The study authors plan to demonstrate their findings' relevance across multiple cancer types. They suggest that by knowing this, they can develop tests that evaluate tumors for patients diagnosed with cancer, look at the Y chromosome, and suggest which treatment will work best.

Since the loss of the Y chromosome triggers cancer growth in the first place, we asked the researchers if men could take steps to limit or prevent this loss. 

Responding to this question, Theodorescu told IE, “There are no ways to truly reverse the chromosome loss but there are ways to mitigate the impact that this loss has on a cell. We are working on some very clever ways to do this right now.”

Also, although women lack Y chromosomes, these findings might reveal valuable insights about certain genes common in X and Y chromosomes and play a role in cancer. However, further research is required to explore such possibilities. 

The study is published in the journal Nature.