JCI: Loss of the Y Chromosome in Men May Be an Early Sign of Cancer

Loss of the Y chromosome in men may occur in tissues before a tumor forms and could serve as one of the early signs of cancer development. This was the conclusion of researchers at the University of Arizona Cancer Center. The findings were published in the journal JCI Insight.

Men typically have one X chromosome and one Y chromosome in their cells. As men age, some cells may lose the Y chromosome—a genetic change that is particularly common in blood cells. The new study showed that a similar process also occurs in tissues of various organs and may be associated with the transition from normal tissue to cancer.

The researchers analyzed approximately 1,000 tissue samples from 405 men. Using automated fluorescence imaging, they examined more than 4.3 million cell nuclei and determined the ratio of X and Y chromosomes.

The researchers studied in particular bladder tissues removed along with tumors. They found a gradual increase in Y-chromosome loss as tissue progressed from apparently normal tissue to early pathological changes and then to established tumors. The closer a tissue sample was to the cancer, the more frequently its cells lacked the Y chromosome.

The most pronounced loss of the Y chromosome in apparently normal tissue adjacent to tumors was observed in cancers of the colon and rectum, esophagus, pancreas, and lungs.

“This pattern may indicate the existence of a precancerous state in which tissue still appears healthy but has already acquired genetic changes that promote tumor development. In the future, this marker could potentially help doctors assess biopsies and identify areas at increased risk,” the researchers explained.

The team had previously found that loss of the Y chromosome directly within cancer cells may help tumors evade the immune response. The new study suggests that Y-chromosome-related changes may emerge even before cancer develops.

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