Wednesday, January 2, 2008

Kaposi’s Sarcoma and the Virus/Cancer Connection (Part 2): In the beginning, there were chickens

On December 15th, I began a discussion about the virus/cancer connection and the role of HHV-8 in causing Kaposi Sarcoma, especially in AIDS patients. Is Kaposi Sarcoma the only cancer caused by a virus? No. In fact, the observation that viruses can cause cancer dates back to the beginning of the 20th century.

In 1909 Peyton Rous discovered that a virus could cause sarcomas in chickens. For discovering the Rous Sarcoma Virus, Dr. Rous was awarded the Nobel Prize in 1966. This discovery led directly to the discovery of cellular oncogenes (genes that cause cancer) by Bishop and Varmus, which also was rewarded with a Nobel Prize.

Subsequently, numerous other human cancers have been associated with viral infections. The most important of these is Burkitt’s lymphoma. Burkitt’s lymphoma comes in three varieties: one form is endemic to sub-Saharan Africa and is most likely caused in large part by infection with a virus called Epstein-Barr Virus (EBV, which also causes mono), one form is sporadic (as opposed to endemic), and one form is associated with immunodeficiencies such as AIDS. The endemic form of Burkitt’s lymphoma typically causes a large, painful jaw mass, while the sporadic form more commonly involved the intestines. Interestingly, another name for EBV is Human Herpesvirus-4 (HHV-4). EBV, or HHV-4, also causes nasopharyngeal carcinoma in southeast Asia (and elsewhere). It is clear that there is a real connection between viruses and cancer.

EBV is a very common virus. According to the Centers for Disease Control, 90-95% of the US adult population has had an EBV infection. When contracted in early childhood, EBV causes the common cold. When contracted during adolescence, the same virus causes mononucleosis 35-50% of the time. While most people who get EBV will not develop cancer, some unfortunately do. Why? No one fully understands yet, but there is a lot of active research trying to better understand the relationship between viruses and cancer.

So maybe we’ll have to change the answer to the question I posed before: Is cancer a contagious disease? No, but contagious diseases might contribute to the development of some forms of cancer. This is why it is important to continue research on understanding and controlling infections.

How do viruses cause cancer? Well, EBV and HHV-8 are both thought to cause cancer by controlling the activity of genes already present in cells called proto-oncogenes. A few years ago, a group of scientists in Spain proposed another way viruses might cause cancer. These scientists were investigating Ewing’s sarcoma (one of my main research interests), the second most common bone cancer in adolescents and young adults.

This is an x-ray of the leg of a patient

with Ewing's sarcoma.

Almost all cases of Ewing’s sarcoma have a particular chromosomal abnormality in them, where a piece of either chromosome 11 or chromosome 21 is attached to chromosome 22. This so-called “translocation” results in the production of a new protein, not found anywhere else in the human body, which is thought to be the direct cause of the cancer.

This is a diagram of a translocation

between two chromosomes.

The Spanish scientists announced, in an article published in 1999, that a gene called E1A (from a kind of cold virus called adenovirus), when put into cervical cancer cells in the laboratory, caused the characteristic translocation between chromosomes 11 and 22 found in Ewing’s sarcoma. Other groups have not been able to repeat this finding, so it remains very controversial, and yet if true, this would suggest that there are numerous ways that viruses could cause cancer in people and would potentially dramatically increase the number of types of cancers that could be related to viruses.


Ben said...

"Subsequently, numerous other human cancers have been associated with viral infections. The most important of these is Burkitt’s lymphoma."

Meh. I'd tend to say that it's cervical cancer these days and its link to HPVs, especially given the advances in prevention methods. They're also turning out to play a significant role in H&N cancers as well. Burkitt's definitely has a greater incidence worldwide though, no?

Doctor David said...

Burkitt's probably does have a greater worldwide incidence, and from a "history of science" perspective is probably also more important (in the sense of having clearly established a link between a common virus and an uncommon cancer, as well as linking a viral infection and a translocation -- though no causative association has been demonstrated). Stay tuned for more about HPV when I get around to writing Part 3!

Ben said...

Awesome...looking forward to it. Have you submitted anything yet to the cancer research carnival? It's coming out tomorrow I believe.

outre said...

Ooh! this post reminded me of when retrovirus particles(or virus like agent, I can't recall exactly) were found in tumors in damselfish neurofibromatosis in mid/late 90s. Totally forgot about that.

Doctor David said...

I didn't know about that! I'll go look it up!

DermDoc said...

I just found you excellent blog from the Medical Weblog awards. Congratulations; after reading through your site I can see it is well deserved.

All the best,

Doctor David said...

Jeff, Thanks for your kind words. I honestly didn't even know I had been nominated, let alone made the finals, until I saw your comment here. I hope you enjoy what you read and come back often.