AmyTuteurMD

AmyTuteurMD
Bio
Dr. Amy Tuteur is an obstetrician-gynecologist. She received her undergraduate degree from Harvard College and her medical degree from Boston University School of Medicine. Dr. Tuteur is a former clinical instructor at Harvard Medical School.

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JANUARY 12, 2009 8:25AM

Does a common virus cause brain cancer?

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In the search for the cause of cancer, viruses were early suspects, but by and large were acquitted of responsibility. Now scientists, aided by a more sophisticated understanding of cancer and armed with more sensitive techniques are reopening the investigation. The latest front is the discovery that glioblastoma, the form of aggressive brain cancer afflicting Senator Ted Kennedy, may be caused by a common virus, cytomegalovirus (CMV). This raises the tantalizing possibility that glioblastoma, notoriously difficult to control with chemotherapy or radiation, might be treated or prevented with a vaccine.

Several forms of cancer have been known to be associated with common viruses. Burkitt’s lymphoma, a fast growing cancer that is rare in the US, but common in Africa is known to be associated with Epstein-Barr virus, the same virus that causes mononucleosis. Liver cancer is known to be associated with hepatitis B and hepatitis C viruses. The association of these viruses with cancer does not necessarily mean that the viruses cause the cancer. It is possible that the virus interferes with the normal immune response, rendering the infected person more likely to develop cancer, or less likely to be able to attack cancer that develops spontaneously in the affected organ.

The first cancer shown to be definitively caused by a virus is cervical cancer. It now appears that virtually all cases of cervical cancer are caused by human papilloma virus (HPV) a common, sexually transmitted virus. Scientists have been able to replicate the malignant changes in HPV cervical cells in the lab, demonstrating cause and effect. That has lead in turn to the development of a vaccine against HPV that should prevent or dramatically reduce the incidence of cervical cancer.

The association between CMV and brain cancer, like many great medical breakthroughs, was discovered by accident. According to Virus in the Brain, in the January 2009 issue of Scientific American Mind:

The saga began in the late 1990s, when Charles Cobbs, a neurosurgeon then at the University of California, San Francisco, started pondering the link between inflam­mation and brain cancer. Malignant tu­mors are often associated with abnormal immune activity, and he wanted to know why. “Is it just something that happens out of the blue, or is it possible that there’s something maybe driving that inflamma­tory cascade?” he recalls wondering.

Because they elicit immune responses, in­fections immediately sprang to mind as pos­sible candidates. Cobbs and his colleagues analyzed glioblastoma samples from 22 pa­tients and found that all harbored CMV. Four out of five people have this virus, which remains in the body for life. Usually a per­son’s immune system keeps CMV in a la­tent state in which it does not replicate, but Cobbs found the virus actively reproducing in these tumor cells and not in healthy cells nearby. “It was stunningly obvious that these tumors were infected,” says Cobbs, whose findings, published in Cancer Research in 2002, were confirmed in 2007 by Duke University neuro-oncologist Duane Mitchell.

Does CMV cause brain cancer?

Cobbs … believes that CMV plays a more active role in generating tumors. He points to a study published in May in Science showing that CMV makes proteins that “turn off” human genes important for preventing unwanted cell growth, a prerequisite to tumor development. It is as if CMV is “clipping the brake line,” re­marks study co-author Robert Kalejta, a molecular virologist at the University of Wisconsin–Madison. Other studies have shown that CMV can interrupt a cell’s ability to commit suicide when the cell growth has gone awry…

These observations do not prove that CMV causes brain cancer. Only lab experiments that show CMV cells becoming cancerous could prove a causal relationship. However, the close association and ability of CMV to turn of the mechanism that usually prevents cancer from developing within a cell means that treating the CMV infection might treat brain cancer or even prevent it.

Cobbs has shown that immune cells sensitized to proteins produced by the CMV virus can identify and destroy CMV infected brain cancer cells. A Swedish group has been investigating the use of anti-viral medications to prevent recurrence of brain cancer treated with chemo or radiation. Perhaps most exciting is ongoing development of a CMV vaccine with the aim of preventing brain cancer. Although the work is still in the earliest stages, the first small trial has shown that the CMV vaccine extends the average survival time for glioblastoma patients from 15 to 20 months. These methods, alone or in combination, may radically change the way that we treat brain cancer and even allow us to prevent it.

The discovery of the association of CMV with brain cancer raises the number of virus associated cancers to four, and suggests that a search for viruses in tumors, using new and more sophisticated tools, may yield new and surprising associations, and open up exciting avenues for treatment and prevention of other types of cancer.

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Very interesting! I'll have to check out the link.
Rob St. Amant:

"Very interesting!"

Yes. It could represent a real paradigm shift in the way we think about cancer.
I recently heard a Talk of the Nation Science Friday edition that talked about a possible link between the TB vaccination and the relative lack of auto-immune disorders in countries where people commonly receive the vaccine. Research is apparently ongoing. There is a lot we don't know yet about disease processes...
Fascinating stuff.

Is it only 4 cancers associated with viruses? I though Kaposi's sarcoma was related to HIV.
Dr. Amy,

While we know there are good bacteria, is there a good virus? If not should the treatment and prevention of all cancers start looking at virus prevention and cure?

Looking at this study, it would not be hard to leap to smoking doesn't cause lung cancer, smoking allows the virus that causes lung cancer to multiply.
Denise Clapsaddle:

"I recently heard a Talk of the Nation Science Friday edition that talked about a possible link between the TB vaccination and the relative lack of auto-immune disorders in countries where people commonly receive the vaccine. Research is apparently ongoing."

That's right. Children who receive the BCG vaccine are less likely to develop autoimmune diseases like juvenile diabetes. There is a trial underway at Harvard Medical School looking at whether BCG can reverse diabetes.
Squillo:

"I though Kaposi's sarcoma was related to HIV."

The association between Kaposi's and HIV is thought to be related to the damage to the immune system. It is probably not cause by HIV directly. It does raise the interesting possibility, though, of other viruses that may damage the immune system and render affected people more vulnerable to specific cancers.
CMV is a scourge. Not only is there this possible brain cancer link, but up to 4% of women contract it for the first time during a pregnancy, putting their baby at risk for congenital CMV which is the leading cause for hearing loss in children 3 and under.

I've been hoping for a CMV vaccine for a long time.
Catnlion:

"Looking at this study, it would not be hard to leap to smoking doesn't cause lung cancer, smoking allows the virus that causes lung cancer to multiply."

Good point. That is definitely possible. Another possibility is that both smoking and viruses cause cancer in the same way, by damaging cell machinery that prevents unlimited growth.
Jacqueline Meyers:

"I've been hoping for a CMV vaccine for a long time."

If the ongoing research is promising, it may be on the horizon.
squillo - there are other virally-induced cancers in animals (and two directly infectious cancers!).

Maybe HTLV, too?
My husband died from glioblastoma. He previously had prostate and colon cancers (both caught early), all three primaries, within three years. I have often wondered if the first two cancers and their treatments weakened his immune system and could have contributed to the glio. He was also under great stress for years and then had these barrage of cancers.
How do you get CMV? I've been reading about CMV in relation to early AIDS cases, but is it sexually transmitted?
My father died from a glioblastoma. Horrible disease. Interesting post.
Unfortunately, we all likely have CMV. I wonder if it is really causing some GBM or just rising from dormancy because of signals from the tumor cells (correlation not being equal to causation).
buckeydoc:

I know about FeLV, what's the other?

Strangely, I don't have CMV--at least that's what they tell me at the blood bank. I also don't (or didn't) have toxoplasmosis, despite having had significant exposure to cat poop, both during my stint as a vet asst. and in caring for my various sick felines. I worried about contracting new infections of both all through my last pregnancy.
squillo - a fellow Toxo-negative person here (and after doing necropsy on 20 kangaroos that died from it!). I suppose we should congratulate ourselves on our good hygiene ;)

For some reason, animals have a lot of oncogenic viruses (at least 20). Besides FeLV, some other big ones are Bovine Leukemia Virus (BLV), Marek's Disease in poultry, Frog herpesvirus (kidney), Mouse Mammary Tumor Virus, Maedi-Visna (lung tumors in sheep), plus poxviruses in many species (sheep, rabbit, squirrel, etc.). The directly contagious tumors are Transmissible Venereal Tumors in dogs - which you might have seen in practice if you're in the south) and Tasmanian Devil Facial Tumor Disease - both kind of gross...
Lea Lane:

"My husband died from glioblastoma. He previously had prostate and colon cancers (both caught early), all three primaries, within three years. I have often wondered if the first two cancers and their treatments weakened his immune system and could have contributed to the glio."

I am so sorry. That must have been unspeakably difficult.

People who get one form of cancer are more likely to get another. Sometimes the treatment is responsible; for example, the treatment for lymphoma may cause leukemia decades later. However, it is more likely to be a genetic problem that makes the body unable to recognize very early cancers and destroy them.
hollycomesalive:

"How do you get CMV?"

According to the CDC:

CMV (cytomegalovirus) is found throughout the world in all geographic and socioeconomic groups, but, in general, it is more widespread in developing countries and in areas of lower socioeconomic conditions.
CMV is a member of the herpesvirus family, which includes the herpes simplex viruses and the viruses that cause chicken pox (varicella-zoster virus) and infectious mononucleosis (Epstein-Barr virus).
CMV is found in body fluids, including urine, saliva (spit), breast milk, blood, tears, semen, and vaginal fluids.
Once CMV is in a person's body, it stays there for life
Most CMV infections are "silent," meaning they cause no signs or symptoms in an infected person.
Transmission of CMV (cytomegalovirus) occurs from person to person, through close contact with body fluids (urine, saliva (spit), breast milk, blood, tears, semen, and vaginal fluids), but the chance of getting CMV infection from casual contact is very small.
So does the Red Cross screen for this when you donate blood?
My mother was just diagnosed with glioblastoma yesterday. I have been scouring the internet for help, sources, etc. I came upon this article. Thank you for writing it . It is the first encouraging thing I have read so far. The Dr's have said that hers is in an unreachable area of her brain and I have been crying my eyes out for the last 24 hours. How did she get this, she was the picture of health. Should I have her tested for CMV ? What do you recommend our first steps should be Dr. ? Things are moving too slowly for me. Where would be the best place in your opinion to take her? Please help us if you can offer any advice I would be most greatful

Thank you for your time

Robert Haddy
If this is true I hope it can save many. My husband of 25 years was diagnoised with GBM in October 08. I lost him on May 16 of this year. Everything under the sun went wrong.