Viral Infections and Colorectal Cancer Risk: Current Research and JC Virus Hypothesis

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• Do Viruses Increase Colorectal Cancer Risk?
• JC Virus and Colon Cancer: The Initial Hypothesis
• Challenges in Proving Viral Cancer Links
• How JC Virus T Antigen Could Transform Cells
• Current Thinking on Viruses and Colon Cancer
• Could Vaccines Prevent Virus-Linked Cancers?
• Full Transcript

Do Viruses Increase Colorectal Cancer Risk?

While genetic mutations and inflammation are well-established risk factors for colorectal cancer, Dr. C. Richard Boland, MD and colleagues investigated whether viral infections might also contribute to colon cancer development. This research was inspired by the proven link between Helicobacter pylori infection and stomach cancer.

Dr. C. Boland, MD, explains that infectious agents can cause chronic inflammation and directly damage DNA - two pathways that could theoretically increase cancer risk. The colon's constant exposure to microorganisms makes it a prime candidate for such virus-cancer connections.

JC Virus and Colon Cancer: The Initial Hypothesis

In the mid-1990s, Dr. Boland's team hypothesized that JC virus, a common polyomavirus, might play a role in colorectal cancer. Their early research using sensitive PCR techniques detected JC virus in most colon tissues examined.

"JC virus infection might explain differences in colon cancer rates between populations," notes Dr. Boland. Initial findings appeared promising, with some laboratories reproducing their results while others could not - a common challenge in viral oncology research.

Challenges in Proving Viral Cancer Links

After two decades of research with improved techniques, Dr. Boland's enthusiasm for the JC virus hypothesis waned. More precise quantification methods revealed JC virus wasn't consistently present in enough colon cancers to support a causal role.

"Most people have JC virus antibodies, meaning we've all been exposed," explains Dr. Boland. This widespread exposure made initial correlations difficult to interpret. Immune response studies comparing cancer patients and healthy controls showed no substantial differences in JC virus immunity.

How JC Virus T Antigen Could Transform Cells

The JC virus theory was biologically plausible because its T antigen protein is a potent cancer-causing agent. "T antigen binds DNA, breaks it, and inactivates crucial tumor suppressor proteins p53 and retinoblastoma," Dr. Boland describes.

In laboratory settings, JC virus T antigen reliably transforms normal cells into cancerous ones. This powerful transforming ability initially made JC virus a compelling candidate for contributing to human colon cancers.

Current Thinking on Viruses and Colon Cancer

While the JC virus hypothesis hasn't been supported by accumulating evidence, Dr. C. Boland, MD, emphasizes the value of exploring infectious causes of cancer. "It's still an interesting idea," he says, "even if the data haven't supported JC virus's role in colon cancer as we initially thought."

The research highlights how difficult it is to prove viral contributions to cancer, especially when the suspected virus is nearly ubiquitous in the population.

Could Vaccines Prevent Virus-Linked Cancers?

Dr. Boland reflects on the appealing concept of cancer-preventing vaccines: "If you could identify a viral cause, you might develop a vaccine against that cancer - like we've done with HPV and cervical cancer."

While JC virus vaccination for colon cancer prevention now seems unlikely, the search continues for other infectious agents that might contribute to gastrointestinal cancers. Such discoveries could one day lead to novel prevention strategies.

Full Transcript

Dr. Anton Titov, MD: Link between viral infection and colorectal cancer. Can viruses increase risk for colon cancer? Can a vaccine reduce colon cancer risk? Leading colorectal cancer genetics expert discusses colon cancer diagnosis and treatment.

Much research has focused on genetic mutations leading to colorectal cancer development. We have just discussed the role of inflammation in cancer development. Inflammation increases the risks for gastrointestinal cancers. There is another important risk factor for cancer: infection.

Dr. Anton Titov, MD: You and your colleagues have investigated potential role of viral infections in colorectal cancer development. What is currently known about the potential role of viruses in colorectal cancer development? What are the controversies and unanswered questions?

Dr. C. Boland, MD: There is no question that Helicobacter pylori infection in the stomach is involved with a lot of stomach cancer. So we were wondering if there was something similar to that infection in the colon that was causing colon cancer.

In the mid-1990s we hypothesized that JC virus might be an infectious agent which contributes to colon cancer formation. JC virus is a polyoma virus. Maybe JC virus infection would explain differences in colon cancer from one population to another.

We used very sensitive PCR-based techniques and found JC virus in most large bowels that we examined. Then some other laboratories tried to reproduce these results, but they could not reproduce them. But other laboratories reproduced our results about JC virus and were able to confirm our data too. All findings were very similar.

T antigen is the transforming factor of JC virus. We found that T antigen was expressed in colon tissues - so JC virus was a very likely culprit. Because JC virus encodes incredibly potent transforming genes that turn cells into cancers. The T antigen binds DNA and breaks it, and inactivates p53 and the retinoblastoma proteins.

T antigen of JC virus is one of the most useful laboratory probes to create cancer.

Dr. C. Boland, MD: To make a long story short, we've gone through about 20 years of doing experimentation. When we finally had much better techniques to quantify JC virus in colon cancers and in a normal colon, it just didn't seem to be present in enough of the colons.

I am now not so certain that JC virus really plays an active role in colon cancer. The problem is that most people have antibodies to JC virus - we have all been exposed to it. So it seemed like it was a plausible contributing factor to colon cancer.

We looked at differences in the immune response to T antigen of JC virus among people who had colon cancers and who did not. There was not a substantial difference.

So JC virus and colon cancer link was an idea that we had for a while. But it's really not an idea that I am very enthusiastic about now. Because the data have not supported what I thought the role for JC virus in colon cancer was in the very beginning.

But it's a very interesting hypothesis. Because if you could identify certain viral infection in cancer, you can invent a vaccine against that cancer. That was the idea from the very beginning. We'd love to come up with just the perfect vaccine to get rid of some kind of cancer. Like getting rid of smoking.