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A study led by Dr. Dan Theodorescu, a physician-scientist at the University of Arizona Cancer Center, found that losing the Y chromosome in men\u2019s body tissue may help cancer develop.<\/strong><\/p>\n Research recently published in JCI Insights shows that losing this chromosome, which often happens as men get older, creates a hidden area of genetic weakness in normal tissue. This makes it easier for cancer to form.<\/span><\/p>\n Normally, each cell in a man\u2019s body has one X and one Y chromosome. \u201cLoss of Y\u201d is a common genetic change where an immune cell in the blood loses its Y chromosome.<\/span><\/p>\n Earlier studies found that losing the Y chromosome in blood cells increases disease risk. This new study looked at Y chromosome loss in normal, precancerous, and cancerous tissues in 11 major organs.<\/span><\/p>\n \u201cWe were able to show that the loss of the Y chromosome is found in normal-appearing tissues adjacent to a tumor,\u201d said Theodorescu, the paper\u2019s senior author and Nancy C. and Craig M. Berge endowed chair and director of the Cancer Center. \u201cThat finding is what makes this discovery so exciting. It suggests we may be looking at one of the earliest signposts of cancer forming.\u201d<\/span><\/p>\n The team studied 1,000 tissue samples from 405 men. They used an automated fluorescent imaging system to examine over 4.3 million cell nuclei and measure the ratio of Y to X chromosomes.<\/span><\/p>\n In one part of the study, researchers made detailed maps of bladder tissue taken during cancer surgery. These maps showed how Y chromosome loss increased from normal tissue to early abnormal cells and then to cancer.<\/span><\/p>\n Loss of the Y chromosome in normal-looking tissue was most common in colon, rectum, esophagus, pancreas, and lung cancers.<\/span><\/p>\n \u201cWe are now thinking of this as a gradient, similar to a hillside that slowly gets steeper,\u201d said Theodorescu, who is also a professor at the U of A College of Medicine \u2013 Tucson. \u201cThe closer the tissue is to a cancer, the more Y chromosome loss we see. That gradient could one day help doctors suspect trouble in biopsies that miss a smaller cancer.\u201d<\/span><\/p>\n