Biography

Dr. Rabkin earned an Sc.B. and M.D. from Brown University and an M.Sc. in epidemiology from the London School of Hygiene and Tropical Medicine. He received postgraduate training at the University of Colorado and is board certified in internal medicine and preventive medicine. Before coming to the NCI, he was an Epidemic Intelligence Service Officer and a medical epidemiologist at the Centers for Disease Control and Prevention. He has received PHS Commendation and Unit Commendation Medals for his studies of non-Hodgkin's lymphoma and Kaposi's sarcoma and the Outstanding Service Medal for the molecular epidemiology of Helicobacter pylori and HIV-related malignancies.

Research Interests

With improvement in the treatment and prevention of opportunistic infections, malignancy is emerging as an important cause of HIV-related morbidity and mortality. Our studies focus on the molecular mechanisms of HIV-related Kaposi’s sarcoma and non-Hodgkin’s lymphoma, and cancers associated with other chronic infections.

Etiologic factors in AIDS-related lymphoma

Cytokine dysregulation is hypothesized to be an important mechanism for AIDS-related lymphoma. Accordingly, we have studied both functional and inherited differences as possible risk factors for this disease. Our methods studies have demonstrated the utility of multiplex cytokine assays for measuring blood levels of circulating cytokines. Ongoing analyses are examining cytokine polymorphisms as risk factors for lymphoma in the Multicenter AIDS Cohort Study and genetic control of cytokine levels in the control subjects of this study. We are also pursuing nested case-control studies of EBV, cytokines, and other factors among cases and controls from the Branch’s cohort studies of HIV infection among homosexual men, hemophilia patients, and AIDS patients. To follow-up on these initial efforts with greater power, we have launched AIDSLymph, a consortium genotyping effort for cytokine and related polymorphisms as risk factors for AIDS-related lymphoma, in collaboration with the North American AIDS Cohorts Collaboration on Research & Design (NA-ACCORD).

Genomic instability in non-Hodgkin lymphoma

Our group has had a long-standing interest in studying the role of specific translocations as precursor lesions in NHL. We recently organized an NCI-sponsored workshop on mechanisms and consequences of chromosomal translocations that brought together epidemiologists and laboratory-based researchers to consider future steps in translocation research, for which the conference proceedings were published in JNCI Monographs. We have also initiated a nested case-control study of translocations and NHL in the Prostate, Lung, Colon, and Ovary Cancer Screening Trial.

EBV in gastric cancer

Some cases of gastric carcinoma have monoclonal EBV genome in every cancer cell, indicating that these tumors arose from a single infected progenitor. However, the proportion of gastric carcinomas that are EBV-positive is uncertain and etiological significance unknown. We therefore investigated EBV antibody patterns among a high-risk population in China and found that elevated titers were associated with progression of gastric dysplasia, suggesting that EBV re-activation may play a role in the pathogenesis. We have also performed a systematic overview of published studies of gastric cancer cases assessed by in situ hybridization for EBV-encoded small RNA. Results from this meta-analysis demonstrated a two-fold differences of EBV positivity by sex and two-fold differences by anatomic subsites and for tumors arising in post-surgical gastric remnants. These differences suggest that EBV-positive gastric cancer is a distinct etiologic entity. Finally, we are organizing a consortium study of a projected 5000 gastric cancer cases to evaluate epidemiologic risk factors for EBV-positive gastric cancers and to compare them to risk factors for the more common EBV-negative tumors. We have started EBV testing of cases from NCI-led studies (total n=1400), and plan to expand the effort into selected extramural studies for which gastric tumor tissue and carefully collected risk factor information is available for study.

Selected Publications

• Wong, H.L. et al. Reproducibility and correlations of multiplex cytokine levels in asymptomatic persons. Cancer Epidemiol Biomarkers Prev 2008, 17:3450-6.
• Hirt, C. et al. Distribution of t(14;18)-positive, putative lymphoma precursor cells among B cell subsets in healthy individuals. Br J Haematol 2007; 138:349-53.
• Rabkin, C.S. and Janz, S. Mechanisms and consequences of chromosomal translocation. Cancer Epidemiol Biomarkers Prev. 2008; 17:1849-51.
• Hold, G.L. et al. A functional polymorphism of Toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors. Gastroenterology 2007; 132:905-12.
• Schetter, A et al. Association of Epstein-Barr virus antibody levels with precancerous gastric lesions in a high risk cohort. Cancer Sci, 2008; 99:350-4.