Loss of function in key Y-chromosome genes increases cancer risk in men

Loss of function in key Y-chromosome genes increases cancer risk in men

News from ISGlobal

Numerous studies have shown that men are more susceptible to cancer than women; however, the reason for this difference remains poorly understood. A new study by researchers from the Barcelona Institute for Global Health (ISGlobal) has identified a key biological mechanism that puts men at higher risk of cancer: loss of function in certain genes of the sex-determining Y chromosome, which is present only in men.

Using data from 9,000 individuals, the researchers studied Y-chromosome gene function in patients with various types of cancer. The findings showed that cancer risk increases with loss of function of six key Y-chromosome genes in various types of cells. "Recent studies have shown that complete loss of the Y chromosome, which is essential to foetal sex differentiation, occurs, with aging, in the cells of some men,” commented Juan Ramón González, coordinator of the study and head of the Bioinformatic Group in Genetic Epidemiology at ISGlobal. “Although the loss of the Y chromosome has previously been associated with higher incidence of cancer, the causes of this association are poorly understood".

"These six Y-chromosome genes are involved in cell-cycle regulation, the failure of which can lead to tumour development. “Interestingly, these genes are matched by a similar copy on the X chromosome", explained Alejandro Cáceres, lead author of the study. "If, as demonstrated, the X-chromosome copy also mutates in the same cells, the protection against cancer that these genes might otherwise provide is lost completely".

You can read more and listen to Alejandro Cáceres explaining the research in ellipse.

Alejandro Cáceres, Aina Jene, Tonu Esko, Luis A Pérez-Jurado, Juan R González. Extreme down-regulation of chromosome Y and cancer risk in men. Journal of the National Cancer Institute, January 2020.

More information:
ISGlobal website