Y chromosome loss could be early cancer sign for men

A recent study published in JCI Insights suggests that the loss of the Y chromosome in men's body tissues may serve as an early indicator of cancer development. As men age, this chromosomal loss becomes more common and creates a preneoplastic field effect, a zone of genetic vulnerability in healthy tissue that allows cancer to thrive.

In men, each cell typically contains one X and one Y chromosome. The loss of the Y chromosome is often seen in immune cells in the blood, and previous research has linked it to higher disease risk. However, this new study provides a more comprehensive analysis of Y chromosome loss across normal, precancerous, and malignant tissues in 11 major human organs.

Senior author Dr. Dan Theodorescu, a physician-scientist at the University of Arizona Cancer Center, notes that finding the loss of the Y chromosome in normal-appearing tissues adjacent to tumors is a significant discovery. The study analyzed 1,000 tissue samples from 405 men, using an automated system to examine over 4.3 million individual cell nuclei and measure the Y to X chromosome ratio.

The researchers created detailed maps of cancerous bladder tissue removed during surgeries, revealing that the loss of the Y chromosome increased as it progressed from normal tissue to early abnormal cells and then to full-blown cancer. The loss of the Y chromosome was most pronounced in colon, rectum, esophagus, pancreas, and lung cancers.

Dr. Theodorescu believes this chromosomal loss forms a gradient, similar to a hillside that becomes steeper as it approaches a cancer. This gradient could potentially serve as an early warning sign for doctors, helping them detect trouble in biopsies that may miss smaller cancers. The study also builds upon previous research by Dr. Theodorescu on how the loss of the Y chromosome in cancer cells enables them to evade the immune system, which may explain the link between Y loss and increased mortality from carcinomas.

Collaborators from Cedars-Sinai Medical Center, Fred Hutchinson Cancer Center, the University of Washington, and the University of California, San Francisco contributed to this research, which was funded in part by the National Cancer Institute.