New research has identified a possible reason as to why some studies say men are more susceptible to cancer than women. The work published in the Journal of the National Cancer Institute reports that the loss of function in certain genes of the sex-determining Y chromosome may play a role in this. The study was carried out in a collaboration between Barcelona Institute for Global Health (ISGlobal), Pompeu Fabra University, the University of Adelaide and the Estonian Genome Centre.

To develop personalised lines of treatment and prevention, a greater understanding of the biological differences between men and women is needed.

The study analysed data from 9,000 patients with various types of cancer and found 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,” said 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.”

The six Y-chromosome genes identified are involved in regulating the cell-cycle, which are key to ensuring the correct replication of cells and whose loss can lead to tumour development. “Interestingly, these genes are matched by a similar copy on the X chromosome,” said 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.”

“Men are not only at higher risk of cancer than women, they also face a worse prognosis,” added González. “In fact, these differences partially account for the lower life expectancy of men.”
“Although men may be more exposed to carcinogens due to the type of work they do and at higher risk because they are less likely to consult a doctor, our study has shown that there are also biological factors that increase cancer risk among men,” commented Cáceres. “In fact, it seems that one of these factors can be found in the Y chromosome, the very essence of maleness.”

This new research gives insights into how the Y chromosome can affect cancer risk through a loss of function or from epigenetic inactivation’s of the regions associated with regulating the cell-cycle.

“Certain environmental exposures, for example, to tobacco or other harmful substances, could affect chromosome function and lead to epigenetic modifications,” said González. “Our findings open the door for the development of targeted detection methods and specific therapies for men with cancer.”