Of Cancer and Men

Of Cancer and Men

The loss of function in genes on the Y chromosome increases the risk of cancer in men

Numerous studies have shown that men are more at risk and less likely to survive cancer than women. However, the reason for this difference is poorly understood. Research by Juan Ramón González, who leads the Bioinformatic Group in Genetic Epidemiology at ISGlobal, and his team, in collaboration with Pompeu Fabra University, the University of Adelaide and the Estonian Genome Centre, has shed some light on this question.

Men are more susceptible to cancer than women

Loss of key genes

The team found that the risk of cancer in men increased with the loss of function of six key genes on the Y chromosome. These genes are involved in cell-cycle regulation, the failure of which can lead to the development of tumours. These genes are matched by a similar copy on the X chromosome. “But if, as as we demonstrated here, the X-chromosome copy also mutates in the same cells, the protection against cancer that these genes might otherwise provide is lost completely,” explains Alejandro Cáceres, lead author of the study. The loss of function of these genes can result from the loss of the Y chromosome, in accordance with previous findings, or the chemical modification of the DNA (epigenetic factors) associated with certain environmental exposures such as tobacco.

Understanding the biological differences between men and women in cancer is crucial for the development of personalised lines of treatment and prevention. “Men are not only at higher risk of cancer than women, they also face a worse prognosis,” says González, head of the Bioinformatic Group in Genetic Epidemiology at ISGlobal.

This study shows that, in addition to behavioural factors, there are also biological factors that increase cancer risk among men. “One of these factors can be found in the Y chromosome—the very essence of maleness,” says Cáceres.

Cáceres A, Jene A, Esko T et al. Extreme down-regulation of chromosome Y and cancer risk in men. J Natl Cancer Inst. 2020 Sep 1;112(9):913-920.

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