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October 25th

Mosaic Loss of Y-Chromosome Associated with Shorter Life Span, Increased Risk of Cancer

Age-related mosaic loss of the Y chromosome (LOY) from blood cells, a frequent occurrence among elderly men, is associated with elevated risk of various cancers and earlier death, according to research presented on Tuesday, October 21, at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego. This finding could help explain why men tend to have a shorter life span and higher rates of sex-unspecific cancers than women, who do not have a Y chromosome, said Lars Forsberg, Ph.D., lead author of the study and a geneticist at Uppsala University in Sweden. LOY, which occurs occasionally as a given man’s blood cells replicate – and thus takes place inconsistently throughout the body – was first reported nearly 50 years ago and remains largely unexplained in both its causes and effects. Recent advances in genetic technology have allowed researchers to use a blood test to detect when only a small fraction of a man’s blood cells have undergone LOY. Dr. Forsberg and colleagues studied blood samples from 1,153 elderly men aged 70 to 84 years, who were followed clinically for up to 40 years. They found that men whose samples showed LOY in a significant fraction of their blood cells lived an average of 5.5 years less than men whose blood was not affected by LOY. In addition, having undergone LOY significantly increased the men’s risk of dying from cancer during the course of the study. These associations remained statistically significant when results were adjusted for men’s age and other health conditions. “Many people think the Y chromosome only contains genes involved in sex determination and sperm production,” said Jan Dumanski, M.D., Ph.D., co-author on the study and a professor at Uppsala University.