Paths Forward in Infection-Related Epidemiologic Cancer Research

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"It would not be surprising if viral infections were eventually shown to be an essential factor in the production of various types of cancer…" We estimate that about 10% of cancer deaths could be attributable to infectious agents. Based on Doll and Peto, 1981External Web Site Policy.

<em>Data source: <a href=''>Global burden of cancers attributable to infections in 2008: A review and synthetic analysis</a>.

Click to enlarge.

Our understanding of the infection-cancer associations has grown since Doll and Peto speculated the potential role of infection in carcinogenesis. Today, infections are established etiologic factors in several cancers and contribute significantly to the global cancer burden. In 2008, it was estimated that 16.1% of newly diagnosed cancers were attributable to infectionsExternal Web Site Policy. The translational potential for this area of research is significant, as the identification of infections associated with cancers may lead to interventions such as treatment or vaccines to prevent associated cancer(s).

Our knowledge of the underlying mechanisms of cancer induction by infectious agents, interactions between the environment and host genetics, and potential roles of cofactors (known and unknown) is limited and warrants further elucidation. Moreover, technological advances have led to the discovery of previously unknown and unsuspected oncogenic infections in recent years; could additional infection-associated cancers be discovered? Epidemiologic studies on this topic could play important roles in answering both old and new questions, which could augment current knowledge and open new areas of research. Understanding the role of infection in cancer may result in discoveries that could lead to better diagnosis, prevention, and treatment of cancers, particularly in resource-poor countries.

Attention has been focused recently on the health-related influence of the microbiomeExternal Web Site Policy. Here, we have chosen to highlight a selection of other potentially innovative areas involving infection and cancer that may warrant further research.

Human liver cells infected with hepatitis C. Image courtesy of Dr. Prokunina-OllsonExternal Web Site Policy, Division of Cancer Epidemiology and Genetics, NCI

The following are important questions for identifying new infections, establishing links with cancer, and developing innovative approaches to detecting or preventing infection-related cancers:

  • Technology/Methods and Infection-Related Cancers: Can novel approaches, coupled with advanced technologies, be used to discover unsuspected oncogenic infectious agents (e.g., viruses, bacteria, fungi)? In recent years, technological advances have led to the discovery of numerous human polyomavirus types. The use of high-throughput sequencing led to the discovery of unsuspected infectious agents that are associated with cancer. For example, by sequencing tumor tissue and subtracting out the human sequences, MExternal Web Site Policyerkel cell polyomavirus and fusobacterium nucleatum were found to be associated with Merkel cell carcinoma and colorectal cancerExternal Web Site Policy, respectively. Novel methods, including capitalizing on bioinformatics tools, could be leveraged to find new infection-cancer associations, such as the relationship between hepatitis C and renal cell carcinomaExternal Web Site Policy.
  • Host-Pathogen Co-Evolution: What is the host-pathogen interaction in carcinogenesis? In some instances, how an individual's immune system responds to an infection may contribute more to the development of cancer than the infection itself. It isplausible that the genetic adaptation of infections within a human host may contribute to cancer development. In addition, the human response to infections is known to be highly heritable. The underlying variants are unknown, however. Could co-evolution between a pathogen and host (e.g., genome-to-genome interaction) explain the interindividual variation response to exposure to a cancer-associated infectious agent? With the co-evolutionary theoryExternal Web Site Policy in mind, cancer epidemiologists could leverage the modern genetic toolkit to investigate, for example, why only a fraction of individuals infected with H. pylori develop gastric cancer. Could advanced technologies, together with new theories, facilitate epidemiologic investigations to explain the opposing risks associated between H. pylori infection and gastric noncardia (higher risk) and gastric cardia adenocarcinoma (lower risk)?
  • Extracellular Vesicles and Cancer: Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication, as they are involved in the transmission of biological signals between cells. A recent in vitro studyExternal Web Site Policy showed that hepatic exosomes, which are a class of EVs, can mediate the transmission of the hepatitis C virus in human hepatoma cells. Are EVs the elusive cofactors in infection-associated liver cancer? Could cancer epidemiologists use EVs to understand why some HBV-/HCV-infected individuals develop liver cancer and some do not? What role do EVs play in liver carcinogenesis?

We Want to Hear From You

Emerging discoveries such as those highlighted here portend new avenues of research in infection-related cancer. We recognize that there are additional ways of investigating infection-related cancers that were not highlighted in this blog. The Epidemiology and Genomics Research Program (EGRP) in NCI's Division of Cancer Control and Population Sciences is interested in hearing your thoughts (in the comment area below) on the future directions of infection-related epidemiologic cancer research.

Tram Kim Lam, Ph.D., M.P.H., is a member of the Knowledge Integration Team and a Program Director in EGRP's Office of the Associate Director and Modifiable Risk Factors Branch (MRFB), respectively. She is involved in a wide range of knowledge-integration projects across EGRP and manages a cross-programmatic research grant portfolio that focuses on genetics, infectious agents, and lifestyle factors that influence susceptibility to cancer.

Danielle Mercatante Carrick, Ph.D., M.H.S., is a Program Director in EGRP's Host Susceptibility Factors Branch (HSFB). She manages a research grant portfolio related to genetic and immunologic factors that influence personal susceptibility to cancer.


  • Dorcas Nduati - June 5, 2015 at 7:38 AM (UTC -4)

    We need to understand cancer properly. Thank you for offering such knowledge.

  • Sandra Milton - July 1, 2015 at 3:55 PM (UTC -4)

    For decades it has been shown infections can cause cancer. It was dismissed as ‘quackery’ by the establishment, while thousands have lost their lives as result of toxic profitable treatment. I have a family member diagnosed with PDAC. I believe the tumor is the result of Clindamycin induced C-Diff infection 2007 (my Dad’s rare post-cricoid hypopharyngeal tumor – result of iatrogenic strep/staph bacteremia). It will be interesting to see how Big Pharma controls infections & cancer in light of old research being re-examined – or if it allows the research to truly ever be delivered on the clinical level that will actually save lives.

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The information on this page is archived and provided for reference purposes only.