The role of microorganisms in the induction of cancer

Cara N. Wilder, Ph.D.

Since the beginning of the 20^th century, microorganisms have been known to play a significant role in the development of cancer in animals¹. However, our understanding on the extent of this issue in humans is still continuing to expand. Currently, it is estimated that microbial infections are linked to approximately 15-20% of human cancers throughout the world^1-3. This presents an enormous potential for the prevention of cancer through the control of infectious disease.

In a 2006 International Journal of Cancer study, it was estimated that the total number of cancers caused by microbial infection in 2002 was approximately 17.8% of the global cancer burden². Of this subset, most of the burden was attributable to viral infections (12.1%), followed by infection with Helicobacter pylori (5.6%), with a small proportion due to parasitic infection (0.1%) (Table 1)². Further, the percentage of these infection-attributable cancers was higher in developing countries as compared to developed countries, reflecting the higher prevalence of these organisms, and perhaps the need for more readily-available healthcare.

Table 1. Examples of microbial-associated cancers^2,4

Agent	Type	Cancer
Epstein-Barr virus (EBV)	Herpesvirus	Hodgkin’s lymphoma, Burkitt’s lymphoma, Nasopharyngeal carcinoma
Helicobacter pylori	Bacterium	Gastric adenocarcinoma
Hepatitis B virus (HBV)	Hepadnavirus	Hepatocellular carcinoma
Hepatitis C virus (HCV)	Flavivirus	Hepatocellular carcinoma
Human herpesvirus 8 (HHV-8)	Herpesvirus	Kaposi’s sarcoma
Human papillomavirus (HPV)	Papillomavirus	Anogenital carcinoma, Oropharyngeal carcinoma
Human T-lymphotropic virus 1 (HTLV-1)	Retrovirus	Adult T-cell lymphoma
Opisthorchis viverrini	Trematode	Cholangiocarcinoma
Schistosoma haematobium	Trematode	Bladder squamous cell carcinoma

The ability of these microorganisms to cause cancer greatly depends on the context of the host-microbial relationship. These interactions can vary significantly due to a number of factors such as the oncogenic potential of the strain, how the strain interacts with the host’s cells and immune system, if the infection causes long-term inflammation, host genotype and phenotype, environmental factors, microbial load, and the composition of the host’s microbiome^1,4. Further, there is some speculation that the ability for certain cancers to run within a family may in part be due to the intra-familial transmission of oncogenic microorganisms. In this latter case, indigenous organisms acquired from a family member may be preadapted to the next host, which could modify the risk of disease^5,6. Regardless of the mechanism, it is clear that preventing or controlling microbial infections may help reduce the number of cancer cases throughout the world.

There are a number of methods that can be used to help prevent cancers associated with microbial infection. Taking measures to avoid exposure to strains associated with infection-attributable cancers, such as circumventing the habitats of harmful species or abstaining from activities that promote transmission, can help reduce the likelihood of infection. Another approach is through the use of vaccination. Currently, vaccines are available against the hepatitis B virus as well as human papillomavirus types 16 and 18. As these vaccines have already demonstrated efficacy in preventing infection, they have the potential to significantly reduce healthcare cost as well as the incidence of liver and anogenital cancer, respectively. If vaccination is not possible, available antimicrobials can be used to help mediate or cure an established infection. For example, in the treatment of H. pylori, the administration of triple therapy regimens for 10-14 days consisting of a proton pump inhibitor, amoxicillin, and clarithromycin are typically recommended, and have reported cure rates from 85-90%⁷.

Overall, infection-attributable cancers represent a significant, albeit preventable, proportion of the global cancer burden. There are currently a number of therapeutic options to help stave off, control, or treat many known oncogenic infections; however, more research is still needed to expand the range of effective therapeutic options as well as help identify additional microbial strains that have the potential to cause cancer. To that end, a number of reputable biological resource centers, such as ATCC, offer a variety of microorganisms, nucleic acids, and cell lines that can be used to help support the research in this field. Only through hard work and dedicated research can we help significantly reduce the number of cancer cases throughout the world.

References

1. American Cancer Society. Infections that can lead to cancer, <http://www.cancer.org/cancer/cancercauses/othercarcinogens/infectiousagents/infectiousagentsandcancer/infectious-agents-and-cancer-intro> (2014).
2. Parkin, D. M. The global health burden of infection-associated cancers in the year 2002. International journal of cancer. Journal international du cancer 118, 3030-3044, doi:10.1002/ijc.21731 (2006).
3. WHO. Global status report on non communicable disease 2010. WHO Library Cataloguing-in-Publication Data (2011).
4. Blaser, M. J. Understanding Microbe-Induced Cancers. Cancer Prevention Research 1, 15-20 (2008).
5. Blaser, M. J. & Kirschner, D. The equilibria that allow bacterial persistence in human hosts. Nature 449, 843-849, doi:10.1038/nature06198 (2007).
6. Blaser, M. J., Nomura, A., Lee, J., Stemmerman, G. N. & Perez-Perez, G. I. Early-life family structure and microbially induced cancer risk. PLoS medicine 4, e7, doi:10.1371/journal.pmed.0040007 (2007).
7. Santacroce, L. & Bhutani, M. Helicobacter Pylori Infection Treatment & Management, <http://emedicine.medscape.com/article/176938-treatment> (2014).