Sex chromosomes shape risk for cancer, heart disease and aging

According to the review led by Dan Theodorescu of the University of Arizona and Dena B. Dubal of the University of California, San Francisco, genes on the X and Y chromosomes influence many aspects of health. They shape immunity, metabolism, brain aging, cancer, and heart disease, independent of hormone levels. The review synthesizes evidence from human studies, mouse models and genomic technologies, arguing that these chromosomes carry instructions that determine how cells age and how our bodies defend against major diseases throughout life.

Y chromosome loss and disease

Loss of a Y chromosome in men, often detected in blood, is linked to higher risk of cancers, heart disease, severe infections and Alzheimer’s disease. In women, loss of an X chromosome is associated with leukemia. Mouse studies show that whether a cell’s active X comes from the mother or father can affect brain aging and memory. These chromosome losses are being explored as biomarkers of age‑related disease and may also contribute to disease progression.

The authors also discuss how the loss of the Y chromosome in cancer cells can help tumors evade the immune system while potentially improving response to immunotherapy. They suggest that understanding these mechanisms could help tailor treatments and diagnostics, making clinical trials sex‑aware and personalized.