A study led by Dr. Dan Theodorescu, a physician and researcher at the University of Arizona Cancer Center, revealed that the loss of the Y chromosome in men's body tissues may pave the way for the development of cancer.
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According to a recent paper published in JCI Insights, the loss of this chromosome, which is common in men as they age, creates a "pre-tumoral field effect," a hidden area of genetic vulnerability in normal tissue that provides fertile ground for cancer development.
The Y chromosome is known as the chromosome responsible for determining maleness in men, as every cell in a man's body normally contains one X and one Y chromosome. With age, some cells lose this chromosome, a common genetic change that occurs when an immune cell in the blood loses its Y chromosome. Previous research has shown that this loss in blood cells increases the risk of disease, but the current study expanded the scope of the investigation to include a systematic analysis of Y chromosome loss in normal, precancerous, and malignant tissues across 11 major organs of the human body.
Theodorescu, lead author of the paper and director of the cancer center, said: "We were able to show that the loss of the Y chromosome is present in tissues that appear normal and are adjacent to the tumor. This finding is what makes this so exciting. It suggests that we may be looking at one of the earliest signs of cancer formation."
The team analyzed 1,000 tissue samples from 405 men, using an automated fluorescence imaging system to examine more than 4.3 million individual cell nuclei and measure the Y-to-X chromosome ratio. As part of the study, the researchers created detailed maps of bladder tissue removed during cancer surgery, allowing them to see how Y chromosome loss increases from normal bladder tissue through early abnormal cells to full-blown cancer. Y chromosome loss in seemingly normal tissue was highest in colorectal, esophageal, pancreatic, and lung cancers.
Theodorescu explained: "What we are seeing now is a clear gradient, like a slope that gradually gets steeper. The closer the tissue is to the cancer, the more Y chromosomes are lost. This means that a doctor may notice this change even in tissues that look normal but are close to the tumor. This gradient may one day help doctors suspect the presence of a small cancer that was not detected by the biopsy, because the sample was taken from an area close to the tumor, even if it did not reach it directly."
Theodorescu's previous research focused on how the loss of the Y chromosome in cancer cells allows them to evade the immune system, explaining why Y loss is associated with increased cancer mortality rates. These findings open the door to the possibility of using Y chromosome loss as an early marker for cancer detection and the development of new treatment strategies.
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