The role of the Y chromosome in cancer outcomes studied

The role of the Y chromosome in cancer outcomes studied

Subject: Science and Technology

Section: Health

Context:

• Two studies have shed light on the role of the Y chromosome in cancer outcomes, in which males are often more adversely affected than females. The results of the studies were published in Nature.

Study findings:

• One paper identified an upregulated gene on the Y chromosome that contributes to colorectal cancer in mice by driving tumour invasion and aiding immune escape in males.
• The other study demonstrated how the loss of the Y chromosome in bladder cancer generates a more immunosuppressive tumour microenvironment and contributes to worse outcomes.

Role of Y chromosome:

• Sex is known to affect cancer incidence, with most cancers causing worse outcomes in males than in females.
• Some studies have suggested that the function of the Y chromosome may have a role.
• Colorectal cancer:
  • Colorectal cancer is the growth of cells that forms in the lower end of the digestive tract. Most of these cancers start as non-cancerous growths called polyps. Removing polyps can prevent cancer, so healthcare providers recommend screenings for those at high risk or over the age of 45.
  • Colorectal cancer is the second most common cause of cancer-related deaths, which is more frequent, aggressive and metastatic in males.
  • Researchers have assessed sex differences in colorectal cancer in a mouse model of the disease.
  • The model is a specific form of the disease, driven by a known oncogene called KRAS. The researchers observed a higher frequency of metastasis and worse survival in male mice, mirroring the outcomes seen in humans.
    • An oncogene is a gene which in certain circumstances can transform a cell into a tumour cell.
  • Analyses reveal the upregulation of a gene for an enzyme which drives tumour invasion and immune escape. This gene is expressed on the Y chromosome, thereby providing a potential basis for sex-specific differences in the progression of KRAS-driven colorectal cancer.
• Loss of Y chromosome:
  • Researchers have also investigated how the loss of the Y chromosome might affect cancer outcomes.
  • Loss of the Y chromosome is a feature observed in multiple cancer types.
  • Tumours lacking the Y chromosome were more aggressive and had a dampened T cell-mediated immune response compared with tumours which had the Y chromosomes intact.
  • The study also noted that the loss of the Y chromosome is associated with an increased response to a specific type of immunotherapy called anti-PD1 checkpoint blockade therapy in both mice and humans, suggesting a potential line of treatment for this subset of bladder cancers.