Why are men more cancer-prone: Answer may lie in the Y chromosome

Several studies have indicated that men are more prone to developing cancer as compared to women, however very little is known about why they display a higher susceptibility towards this deadly disease.

A new study by researchers from the Barcelona Institute for Global Health (ISGlobal), has pinpointed the loss of function in certain genes of the sex-determining Y chromosome as a key factor that puts men at higher risk of cancer.

In the study that was published in the Journal of the National Cancer Institute, scientists used data from 9,000 individuals and 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 ageing, in the cells of some men," commented Juan Ramon Gonzalez, coordinator of the study and head of the Bioinformatics Group in Genetic Epidemiology at ISGlobal.

"Although the loss of the Y chromosome has previously been associated with a 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 Caceres, 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, but they also face a worse prognosis," commented Gonzalez. "In fact, these differences partially account for the lower life expectancy of men."

Identifying the factors that make men more vulnerable to cancer is an important line of research that has the potential to mitigate risk in this population.

"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 Caceres. In fact, it seems that one of these factors can be found in the Y chromosome, the very essence of maleness."

According to the authors of the study, suppression of the Y chromosome can occur as a result of the loss of function in the chromosome, which would explain previous findings, or as a result of other mechanisms mediated by the chemical (epigenetic) inactivation of the same regions.

"Certain environmental exposures, for example to tobacco or other harmful substances, could affect chromosome function and lead to epigenetic modifications," commented Gonzalez.

The understanding of biological differences between men and women in terms of cancer would prove to be crucial for the development of personalised lines of treatment and prevention.