New Immunity and Inflammation Planning Group

At a recent DCEG Senior Advisory Group retreat, the group identified a number of broad areas of interest that are central in the Division’s work to understand the etiology of cancer (see Linkage, November 2008). Toward this end, a series of planning groups was established to enable strategic planning in genome-wide association studies, environmental and dietary exposure assessment, development of mission-critical high-throughput laboratory services, biorepository enhancements, investigations into tumors that are highly lethal (e.g., liver cancer) or rising in incidence (e.g., thyroid cancer), and the role of inflammatory and immunological processes in carcinogenesis.

Altered immunity and chronic inflammation appear to play a key role in the etiology of several malignancies. A number of cancers are directly linked to oncogenic viruses and bacteria. Immunosuppression results in poor control of these infections, in some cases dramatically amplifying cancer risk (e.g., Epstein-Barr virus and certain lymphomas; human herpesvirus 8 and Kaposi sarcoma). In other cases, infection-associated inflammation is crucial to the development of cancer (e.g., hepatitis C virus and hepatocellular carcinoma; Helicobacter pylori and gastric cancer). Immune disturbances and chronic inflammation are also implicated in other malignancies not associated with infections. For example, chronic autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosis, and Sjögren’s syndrome are associated with increased risk of non-Hodgkin lymphoma, likely due to chronic immune activation. Tuberculosis and pulmonary scarring have been linked to an increased risk of lung cancer, while use of non-steroidal anti-inflammatory drugs appears to reduce colon cancer risk. Polymorphisms in genes related to immunity and inflammation have been associated with altered susceptibility to several malignancies.

DCEG is conducting a strategic planning process to coordinate the Division’s molecular epidemiology research activities in this important area. The process is coordinated by the Inflammation, Immunity, and Cancer Steering Committee, cochaired by Eric A. Engels, M.D., M.P.H., Infections and Immunoepidemiology Branch (IIB), and Patricia Hartge, Sc.D., Deputy Director of the Epidemiology and Biostatistics Program. Other members include James J. Goedert, M.D. (IIB), Allan Hildesheim, Ph.D. (Chief of IIB), Ann W. Hsing, Ph.D., Hormonal and Reproductive Epidemiology Branch (HREB), Martha S. Linet, M.D., M.P.H., Chief of the Radiation Epidemiology Branch, June A. Peters, M.D., C.G.C., Clinical Genetics Branch, Ruth M. Pfeiffer, Ph.D., Biostatistics Branch, Ligia A. Pinto, Ph.D. (IIB), Mark Purdue, Ph.D., Occupational and Environmental Epidemiology Branch, and Sophia S. Wang, Ph.D. (HREB).

The committee has identified important gaps in knowledge, which may serve as opportunities for collaborative research involving epidemiologists and laboratory scientists. Measurement of tumor-related inflammatory processes is difficult due to the inaccessibility of these tissues for sampling. The precise inflammatory and immune pathways that connect predisposing disease states (e.g., infections and autoimmune diseases) to cancer remain to be elucidated (see figure 1). The biological effects of common genetic polymorphisms on the immunological and inflammatory response are unknown.

Figure 1. Proposed causal pathways of inflammation to cancer.

To address these questions and facilitate epidemiologic investigations, the steering committee established working groups in four specific areas. These groups have recruited investigators from across the Division and will continue to serve as a forum for communication, planning, and collaboration. One group is engaged in the development and validation of a panel of blood biomarkers of the immune/inflammatory response, suitable for large-scale multiplex assessment. A second group is coordinating efforts to optimize tissue markers that can be utilized in the molecular evaluation of tumors in epidemiologic studies. Another working group is summarizing DCEG’s portfolio of linked registry resources that can be used for new studies of immune-related medical conditions in association with cancer risk. A fourth working group provides a forum for investigating the interface of environmental and biobehavioral risk factors with chronic inflammation, altered immunity, and cancer.

Finally, in developing a program of molecular epidemiology in this area, the planning group will coordinate efforts and seek out collaborations with immunologists in the Center for Cancer Research and the recently developed NIH Center for Human Immunology. The intramural clinics and laboratory sciences at NIH are rich in the field of immunology, and their contributions will be critical to the success of interdisciplinary population-based studies in this area.

—Eric A. Engels, M.D., M.P.H.

Back to Top