A genetic riddle hidden in male DNA may finally explain why men face higher cancer risks in shared organs—and could unlock new treatments.
Men with complete or partial loss of Y chromosome (LOY) in tumors exhibit elevated cancer incidence and severity in bladder, gastric cardia, and larynx cancers.
By age 70, approximately 40% of men have lost the Y chromosome in blood cells, while 30% of male primary tumors show LOY. In papillary renal cell carcinoma, LOY prevalence may reach 80%.
Dr. Luis Antonio Corchete Sánchez explained: "You’ve lost those books forever; you can never recover that information." The Y chromosome contains tumor-suppressing genes, and its loss removes this protective mechanism.
However, causality remains unproven: "Is LOY oncogenic on its own, or does it need collaborators? That’s something we simply don’t know yet."
Dr. Esther Rheinbay highlighted a potential treatment pathway: "LOY in cancer cells leads to this exposed X chromosome... we can potentially treat those cancer cells." Researchers suggest LOY may create therapeutic windows for targeted treatments, though only one prospective trial has been completed to date.
In the article, LOY stands for “loss of the Y chromosome.” It refers to a situation in which the Y chromosome disappears from cells either partially or completely — especially in tumor cells. Researchers are studying LOY because it may help explain why men have higher cancer risks and more severe disease in some types of cancer, and because genes on the Y chromosome that normally help suppress tumors are lost when LOY occurs.
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