Source – The Hindu
Why in discussion?
Recent research has shown that the Y chromosome and cancer susceptibility are interrelated, with studies showing how males are more susceptible to certain types of cancer.
This study sheds light on the role of the Y chromosome in colorectal and bladder cancer, providing insight into key genetic mechanisms influencing tumor development, immune system response, and clinical prognosis.
Colorectal and bladder cancer:
Cancer:
- Cancer is a collection of disorders marked by the uncontrolled growth and proliferation of abnormal cells in the body.
- Cancer cells (abnormal cells) are capable of affecting and destroying healthy tissues and organs.
- In a healthy body, cells normally grow, divide, and eventually die in a regular manner, allowing tissues and organs to function normally.
- However, in the case of cancer, certain genetic mutations or abnormalities disrupt the normal cell cycle, causing cells to divide and multiply uncontrollably.
- These cells can form a group of tissues called a tumor.
colorectal cancer:
Colorectal cancer is also known as colon cancer or rectal cancer. This refers to cancer that develops in the colon or rectum, which are parts of the large intestine.
It is one of the most common types of cancer worldwide.
It usually begins as small, noncancerous growths called polyps on the inner lining of the large intestine (colon) or rectum. Over time some of these polyps can become cancerous.
Bladder cancer:
Bladder cancer refers to the growth of cancer cells in the tissues of the bladder where urine collects.
Key findings of the study:
Role of Y chromosome in colorectal cancer in men:
- Studies have examined gender differences in colorectal cancer using a mouse model driven by an oncogene called KRAS.
- The research found that male mice had a higher frequency of metastasis (the spread of cancer cells from the site of origin of the tumor to other parts of the body) and had a much lower survival rate than female mice, mirroring results seen in humans. does.
- They also identified an upregulated gene on the Y chromosome that causes men to develop colorectal cancer by reducing tumor risk and immunity.
- It acts by repressing genes that stimulate the immune response, as well as activating genes that promote cell migration, invasion, and angiogenesis (formation of new blood vessels).
NOTE: KRAS is a gene that encodes a protein called Kirsten Rat Sarcoma Viral Oncogene Homolog. It is a proto-oncogene, meaning it has the potential to become a cancer-causing gene.
Effect of Y chromosome loss on bladder cancer outcomes:
- A separate investigation looked at the effect of loss of the Y chromosome on bladder cancer outcomes.
- As men age, cells lose the Y chromosome and cancer cells promote the destruction of the male immune system.
- Loss of the Y chromosome has been found to be associated with misdiagnosis and more aggressive tumors.
- This situation has generated a more immune suppressive tumor microenvironment by altering the expression of genes involved in immune regulation.
- For example, loss of the Y chromosome increased expression of PD-L1, a protein that inhibits T cell activation and promotes immune system elimination of cancer cells.
- However, the finding that Y chromosome deletion improved response to anti-PD1 inhibitor therapy points to a viable therapeutic avenue for a subset of bladder malignancies.
- This suggests that loss of the Y chromosome has potential as a biomarker for the selection of patients who may benefit from this treatment.
