Viruses and Cancer Flashcards
What proportion of cancers are caused by infection?
What proportion of cancers are caused by viruses?
- 15% of cancers are caused by infection.
- 10% of cancers are caused by viruses.
List 6 type 1 carcinogenic viruses.
Give an example of a cancer caused by each virus.
1 - Epstein-Barr virus.
- Burkitt’s lymphoma.
2 - Kaposi sarcoma-associated herpes virus.
- Kaposi sarcoma.
3 - Hepatitis B virus.
- Hepatocellular carcinoma.
4 - Human T-cell lymphotropic virus type 1.
- Adult T-cell leukaemia.
5 - HIV type 1.
- Lymphoma.
6 - HPV 16 and 18.
- Squamous cell carcinomas (almost all cases of cervical cancer are caused by HPV).
What is the difference between a direct carcinogen and an indirect carcinogen with regards to carcinogenic viruses?
- Direct carcinogens cause cancer through viral oncogenes that directly contribute to cancer cell transformation.
- Indirect carcinogens cause cancer through chronic infection, inflammation and immunosuppression, leading to carcinogenic mutations in the host.
List 3 direct carcinogenic viruses.
Direct carcinogenic viruses:
1 - Human papilloma virus.
2 - Epstein-Barr virus.
3 - Kaposi sarcoma-associated herpes virus.
Give an example of an indirect carcinogenic virus.
HIV is an indirect carcinogenic virus.
What are Koch’s postulates?
List the 4 postulates.
- Koch’s postulates are postulates for identifying an infectious agent as the cause of a specific disease.
1 - The infectious agent is regularly found in the lesions of the disease.
2 - The infectious agent can be isolated in cultures from fluids or tissues of an organism with the disease.
3 - Inoculation of this culture into a susceptible host produces the same disease.
4 - The disease can be indefinitely transmitted by the recovered infectious agent.
List 2 factors that make it difficult to identify an infectious agent as the cause of a specific disease.
1 - There is a long latency period between primary infection and tumour development.
2 - Only a small proportion of virus-infected individuals develop a tumour.
3 - The pathogenesis of tumour development due to infection is complex and has many cofactors.
4 - The viral genome can be disrupted in the cancer.
5 - There are no experimental animal models for the human cancers.
To which family of viruses does EBV belong?
Give an example of a condition caused by EBV.
- EBV is a herpesvirus.
- Infectious mononucleosis (glandular fever) is caused by EBV.
What proportion of the world’s population is infected with EBV?
95% of the world’s population is infected with EBV.
*EBV is usually latent for life.
Give an example of a mutation that is commonly found in cancers associated with EBV.
In cancers associated with EBV, the MYC oncogene is often translocated to an immunoglobulin promotor region, which is highly active in immune cells.
*Remember EBV causes Burkitt’s lymphoma.
What is the most common cause of merkel cell carcinoma?
The most common cause of merkel cell carcinoma is merkel cell polyomavirus.
*This is actually a common infection but only a small proportion cause tumours.
What is the average life expectancy of patients with merkel cell carcinoma?
The average life expectancy of patients with merkel cell carcinoma is 9 months or less.
How does the mechanism of polyomavirus infection differ in cases where the virus causes cancer compared to when it does not cause cancer?
When polyomavirus causes cancer, it incorporates its genetic material into the host cell’s DNA (whereas it usually does not).
List 2 viral oncoproteins that are coded by HPV.
HPV viral oncoproteins:
1 - E6.
2 - E7.
Describe the mechanism by which HPV increases the risk of developing cancer.
- The HPV virus infects the deep basal cells of the epithelium, as the basal cells are mitotically active.
- As the epithelial cells become specialised and mitotically inactive as they become more superficial, the HPV forces the cells back into the cell cycle. It does this using E6 and E7 proteins:
1 - E7 activates the genes of the host cell that are necessary for DNA replication by interacting with pRb protein. *more on this on another card
2 - In response to this inappropriate inactivation of oncogenes, the cell responds by inducing apoptosis via p53.
3 - However, E6 combines with a host cell factor known as E6a to degrade p53 and prevent apoptosis.
- Deregulation of both pRb and p53 tumour suppressor pathways promotes host genome instability, increasing the risk of acquiring an oncogenic mutation (which can then be induced by cofactors, e.g. smoking).
