Recently, an article was published in Nature outlining the results of two scientific studies focused on exploring the role of the Y chromosome in aggressive behaviors of two cancer types in men, namely colorectal and bladder cancer.
Human Chromosomes
It is previously known that men are more likely to develop many cancers as compared to women. Overall, the risk of developing cancer is nearly equal for men and women over their lifetime, but the higher risk in men for certain cancers is well recognized.
Do lifestyle factors explain higher cancer rates in men?
The underlying reasons for this disparity are not clearly understood. Generally, lifestyle factors like higher rates of smoking and alcohol use, dietary differences, and less utilization of preventative health care approach like cancer screening by men have been used to explain the higher risk for certain cancers for men.
Are certain tumors more aggressive in men?
Another observation about tumor behavior in men is that many cancers behave aggressively in men as they develop quickly and spread to other sites of the body rapidly. In general, the outcomes of these aggressive tumors in men tend to be poor.
A paucity of genetic explanations
In medical research, the underlying molecular and genetic factors for higher cancer rates and increased severity in men have largely been unexplored. This is possibly due to a keen focus on exploring lifestyle and behavioral risk factors. In addition, the genetic explanations are focused on the role of the X-chromosome gene previously.
The author presented findings from two recently published studies in the article published in Nature. These studies have explored the role of the Y-chromosome in tumor behavior in men.
Loss of the Y chromosome makes bladder cancer cells more aggressive
One study revealed the critical role of the loss of the Y chromosome in driving the aggressive behavior of bladder cancer cells. Scientists at the Cedars-Sinai Medical Center in Los Angeles, California, knew that the Y-chromosome could be lost during cell division, and it had a role in different diseases like heart diseases, neurodegenerative diseases, and cancers. The scientists observed that when these cancer cells with the lost Y-chromosome were transplanted in mice, they showed aggressive behavior, and their surrounding immune cells didn’t seem functional. These findings have shown a reciprocating trend in human tumors, according to the researchers.
Role of KDM5D in colorectal cancer behavior
The second study by a team of researchers at the University of Texas MD Anderson Cancer Center in Houston explored the role of a gene called KDM5D, present on the Y chromosome, in driving the invasion and spread of colorectal cancer. Scientists learned that this gene helps the cancer cells invade the surrounding tissues and facilitates their spread to other parts of the body. Scientists also observed the less invasive behavior of the tumor cells when they deleted this gene.
How do these results help in finding cancer treatment?
Overall, the author mentions the significance outlined by the scientists. These results are essential in finding new treatments for these types of cancers, as these findings help identify new targets for anti-cancer drugs. Another significant point is that these study results point a direction for finding the role of Y-chromosomes in the behavior of other types of tumors. Further research may explore the effect of losing the Y-chromosome and the role of genes on the Y-chromosome on different cancers and, possibly, lay out pathways for developing new treatment options for those cancer types.
References
Callaway, E. (2023). How the Y chromosome makes some cancers more deadly for men. Nature. Retrieved from https://www.nature.com/articles/d41586-023-01987-x
Abdel-Hafiz, H. A., Schafer, J. M., Chen, X., Xiao, T., Gauntner, T. D., Li, Z., & Theodorescu, D. (2023). Y chromosome loss in cancer drives growth by evasion of adaptive immunity. Nature. https://doi.org/10.1038/s41586-023-06234-x
Li, J., Lan, Z., Liao, W., Horner, J. W., Xu, X., Liu, J., Yoshihama, Y., Jiang, S., Shim, H. S., Slotnik, M., LaBella, K. A., Wu, C., Dunner, K., Hsu, W., Lee, R., Khanduri, I., Terranova, C., Akdemir, K., Chakravarti, D., Shang, X., Spring, D. J., Wang, Y. A., & DePinho, R. A. (2023). Histone demethylase KDM5D upregulation drives sex differences in colon cancer. Nature, 2023. https://doi.org/10.1038/s41586-023-06254-7
