Abstract B06: Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma

Background: Esophageal cancer is a leading cause of cancer-associated deaths worldwide. Notably, there is a disproportionately high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa. One possible explanation for the unique geographic distribution of ESCC may be the human microbiome, which has been shown to influence other gastrointestinal (GI) cancers, including gastric and colorectal cancer (CRC). Methods: To address this question, we conducted RNA sequencing (RNAseq) and whole-genome sequencing (WGS) of samples from 61 Tanzanian ESCC patients. We used the computational microbial identification and classification software PathSeq to conduct a microbial abundance analysis of these samples. Next, we implemented linear discriminant analysis with LEfSe to determine which, if any, microbial taxa are enriched in the ESCC tumors of Tanzanian patients relative to ESCC samples from North America patients available through The Cancer Genome Atlas (TCGA). Results: Analysis of these RNAseq and WGS data reveals an extremely high abundance of Fusobacterium, Prevotella, and Streptococcus in the tumors of a subset of these patients. Based on the WGS data in particular, 14, 45, and 27 of the 61 ESCC samples maintain at least 10% relative abundance of Fusobacterium, Prevotella, and Streptococcus, respectively. The RNAseq data are consistent and reveal that as much as 75% of all bacterially derived reads in these samples are from these genera. Furthermore, LEfSe analysis suggest that these bacteria are significantly enriched in Tanzanian ESCC samples compared to North American ESCC samples. Discussion: These data suggest that the microbiome may be involved in ESCC incidence in Tanzania. Fusobacterium, Prevotella, and Streptococcus are notable for their association with CRC and are correlated with distinct clinical and molecular CRC characteristics. Members of these bacterial genera have been observed to modulate the carcinogenesis of GI cancers in a variety of ways, including through the selective stimulation or inhibition of various classes of immune cells. Furthermore, species within these genera have been observed invasively within cancerous GI tissues. Current studies are under way to visualize these microorganisms in tumor tissue, to characterize their association with molecular subtypes of ESCC, and to understand the relationship between tumor-associated bacteria and bacteria in the oral microbiome of ESCC patients in Tanzania. Citation Format: Jason Nomburg, Susan Bullman, Eric Collisson, Beatrice Mushi, Msiba Seleka, Charlie Vaske, Yulia Newton, Amie Radenbuagh, Larry Akoko, James A. DeCaprio, Matthew Meyerson, Elia J. Mmbaga, Katherine Van Loon. Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B06.