A new study led by a University of Arizona Cancer Center physician-scientist has found that the loss of the Y chromosome in men’s normal-looking body tissue may create a hidden genetic environment that allows cancer to develop, potentially providing an early warning sign of the disease.
The research, led by Dr. Dan Theodorescu, it suggests that the loss of the Y chromosome can produce what scientists describe as a pre-neoplastic field effect an area of tissue that appears normal but contains genetic changes that may make it more vulnerable to cancer.
Men’s cells typically carry one X chromosome and one Y chromosome. As men age, some cells, particularly immune cells in the blood, can lose the Y chromosome. This genetic change, known as “loss of Y."
For the new study, researchers examined the role of Y chromosome loss more broadly by analyzing normal, precancerous and cancerous tissue from 11 major organs. The team studied 1,000 tissue samples collected from 405 men and used an automated fluorescent imaging system to examine more than 4.3 million individual cell nuclei.
The researchers found that Y chromosome loss was also present in tissue that appeared normal but was located next to cancerous tumors.
“We were able to show that the loss of the Y chromosome is found in normal appearing tissues adjacent to a tumor,” Theodorescu said. He described the finding as significant because it could represent one of the earliest detectable signs of cancer development.
Researchers also created detailed maps of bladder tissue removed during cancer surgery. The maps showed an increase in Y chromosome loss as tissue changed from normal to early abnormal cells.
The highest levels of Y chromosome loss in normal-appearing tissue were observed near cancers of the colon, rectum, esophagus, pancreas and lung. Theodorescu compared the pattern to a gradually steepening hillside.
The researchers said the pattern could eventually help doctors identify potential cancer-related changes in biopsy samples, particularly when a small tumor is missed during the initial examination. The findings build on Theodorescu’s earlier research into Y chromosome loss in cancer cells.
The new findings point to a possible role for Y chromosome loss not only inside cancer cells but also in nearby tissue that still appears healthy. Researchers say further work will be needed to determine whether the chromosome loss can reliably serve as an early indicator of cancer and how it might be used in clinical care.
