Cause or consequence? Microbe associated with Cancer

A recently published study has found an association between a microbe commonly associated with the development of dental plaque and… colorectal cancer. It’s time we had a discussion about association and causation and then we can look at the implications of this research.

Colorectal cancer is a serious disease which, according to the World Health Organization, accounts for about 610,000 deaths per year. As you can probably imagine, significant resources are being pumped into understanding the causes, consequences, and development of treatments. A continuing theme of this research is that gut inflammation is a recognised risk factor and that infectious agents might be responsible. This thought was behind the discovery of an association between  Helicobacter pylori and stomach ulcers. According to this new research (freely available), published 18th October 2011, the same might be true for a microbe called Fusobacterium nucleatum and colorectal cancer.

The essentials of the discovery are as follows. After screening colorectal cancer tissue specimens and matched controls, the researchers (to their apparent surprise) found a significant over-representation of genetic material from Fusobacterium nucleatum associated with tumors. They managed to do this by matching up sequences of the material with those in genome databases after excluding any human genetic material (technically this is an application of an approach called metagenomics). What is surprising about the association is that F. nucleatum is normally associated with dental plaque formation and is not widely regarded as a significant member of the gut microbiota. So, is the result plausible? Yes. And, have we discovered the root cause of colorectal cancer? The short answer is no, not yet.

This discovery is an association. The microbe happens to be present more when there is a tumor. It may represent an opportunistic infection of compromised tissue but then it might be involved in some sort of inflammatory process. It is just too early to say. As the authors rightly point out, translating this to causation will require much more work. The evidence is mounting, however. The obvious question to ask next is whether fusobacteria are elevated in patients with colorectal cancer. Usefully another study, published at the same time, seems to indicate this might be the case.  We will now have to wait for further confirmation of these interesting results.

So, what are the implications of this research? Suppose we unequivocally determine that fusobacteria are involved in the development of colorectal cancer. This would suggest it might be a suitable target for vaccination or some sort of antimicrobial therapy. If it eventually proves to just be an association, screening for the microbe might be useful for early stage diagnosis and risk reduction.

Vaccinating against such a bug and such a serious disease really would be a significant medical advance. We will just have to hold tight for that day to come.

References

Castellarin et al (2011). Fusobacterium nucleatum infection is prevalent in colorectal carcinoma. Genome Research. Published online 18th October 2011. DOI: 10.1101/gr.126516.111

Kostic et al (2011). Genomic analysis identifies association of Fusobacterium with colorectal carcinoma . Genome Research. Published online 18th October 2011. DOI: 10.1101/gr.126573.111