Abstract
Abstract A clear intersection between the infectious diseases and oncology fields has emerged from our understanding that many cancers arise in the setting of chronic infection. Roughly one-third of cancers worldwide, particularly epithelial cancers, are associated with identified single microbial infections, leading to the conceptual paradigm that chronic infection with specific microbes cause these cancers independent of other components of the ambient microbial community. Among epithelial cancers, colon cancer is the second leading cancer killer of adults in the United States but specific microbial contributors have not yet been identified. Rather, we now understand that the colon is home to one of the most dense and diverse communities of bacteria in the body and that we are each remarkably unique in our bacterial makeup, reinforcing the contrasting view that the microbial contribution to colon cancer pathogenesis may lie in the composition of the colon microbiome. This talk will explore the scientific data supporting differing paradigms for how the colonic flora may contribute to colon oncogenesis. Specific, usually commensal, members of the colonic microbiome and the mechanisms by which they may initiate and/or promote colon tumors with be discussed with a particular emphasis on enterotoxigenic Bacteroides fragilis (ETBF). B. fragilis not only colonizes most humans but is the leading anaerobe in human disease. ETBF is a molecular subset of B. fragilis distinguished by secretion of a zinc-dependent metalloprotease toxin. In murine models, ETBF is a potent inducer of colonic tumors. Tumor induction by ETBF is dependent, in part, on a specific host immune response involving IL-17-producing CD3+CD4+ T cells. A framework for utilizing this knowledge to better understand the pathogenesis of colon cancer and to develop new approaches to colon cancer prevention and/or therapy will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY27-01. doi:10.1158/1538-7445.AM2011-SY27-01
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