Charles S. Rabkin, M.D., M.Sc.
Viral Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA
(Tel: +1 301-496-8115 Fax: +1 301-402-0817 E-mail: rabkinc@mail.nih.gov)
Inflammatory and immune reactions to pathogens are coordinated by a complex network of secreted cytokine proteins. While generally favorable to the host, the cytokine repertoire is sometimes subverted by bacterial or viral infections to prevent clearance or increase tissue distruction. For example, Helicobacter pylori infection induces marked inflammation of the gastric mucosa, with increased levels of pro-inflammatory (e.g., IL-1, IL-6, and TNF-alpha) and chemotactic (such as IL-8 and GRO-alpha) cytokines, as well as anti inflammatory cytokines (such as IL-4 and IL- 10) which modulate inflammation and promote specific immunity. Functional polymorphisms in the genes controlling cytokine expression may determine the difference between self limited infection and severe chronic gastritis, an initiating lesion in gastric carcinogenesis (1). Likewise, human immunodeficiency virus (HIV) infection is associated with systemic disruption of steady-state cytokine signalling, including increased production of pro-inflammatory cytokines and interferon gamma as well as decreased production of IL-2. In concert with herpesvirus co factors, this dysregulation permits uncontrolled proliferation of B-lymphocytes and spindle cells and their respective tumors, non-Hodgkin's lymphoma and Kaposi's sarcoma. Correspondingly, interleukin and chemokine gene polymorphisms also influence risk of these AIDS-related malignancies (2). Recognition of these disease associations with cytokine gene variation should lead to enhanced understanding of the underlying pathogenesis of infection related cancers and suggest improved strategies for treatment and prevention.
References:
(1) El-Omar et al (2000). Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398-402.
(2) Rabkin et al (1999). Chemokine and chemokine receptor gene variants and risk of non-Hodgkin's lymphoma in human immunodeficiency virus- I -infected individuals. Blood 93:1838-42.
Charles S. Rabkin, M.D.1978 Sc.B. Brown University, Providence, RI
1981 M.D., Brown University Program in Medicine
1981-84 Internal medicine resident, U. of Colorado
1984-86 EIS Officer, New York City Health Dept.
1985-87 Preventive medicine resident, CDC
1988 M.Sc. (Epi), London School of Hygiene &TM
1989-92 Medical epidemiologist, NCI
1995-98 Visiting fellow, Johns Hopkins University
1992-pres HIV-Cancer Coordinator, NCI
Speciality and Special Interest:
Molecular mechanisms of HIV-associated malignancies and infection-related gastrointestinal cancers.