Loss of Y chromosome in men could be an early warning sign of cancer

A study led by Dr. Dan Theodorescu at the University of Arizona Cancer Center suggests that the loss of the Y chromosome in men's body tissue could serve as an early indicator of cancer development. Published in JCI Insights, the research found that this loss, common in aging men, establishes a genetic vulnerability in normal tissue, providing an environment conducive to cancer growth.

Typically, cells in men's bodies contain one X and one Y chromosome; however, the loss of Y is prevalent in immune cells found in the blood. Previous studies indicated that Y loss in blood cells elevated disease risk, but this comprehensive study examined Y loss across normal, precancerous, and malignant tissues in 11 major human organs.

The researchers discovered that Y chromosome loss is present in seemingly normal tissues adjacent to tumors, which is a significant finding as it may represent one of the earliest signs of cancer. The team analyzed 1,000 tissue samples from 405 men, using an automated fluorescent imaging system to examine over 4.3 million cell nuclei and assess the Y to X chromosome ratio.

Detailed maps of bladder tissue removed during cancer surgery revealed that the highest concentration of Y loss occurred in colon, rectum, esophagus, pancreas, and lung cancers. This gradient of Y loss, moving from normal tissue to cancer, could potentially assist doctors in identifying suspicious biopsies that might miss smaller tumors, thereby highlighting the potential of Y chromosome loss as an early warning sign for cancer.