Abstract B33: Racial differences in tumor-associated microbes in early colorectal carcinogenesis

Abstract

Abstract African Americans (AA) have a higher incidence of colorectal cancer (CRC) than Caucasian Americans (CA). Emerging evidence indicates that pathogenic tumor-associated microbes (TAMs) within preinvasive lesions may promote carcinogenesis. Since AAs are more prone than CAs to robust inflammatory responses to bacteria and fungi, especially at younger ages, infiltrates in early neoplasms may differ by race and age. To study this issue, we selected a convenience sample of 35 preinvasive cases diagnosed between October 2013 and October 2016 at the Medical University of South Carolina for microbial analysis. The study pathologist diagnosed the degree of dysplasia and predominant histology for each lesion. We extracted DNA from 10-micron-thick FFPE sections and sequenced 16S rRNA gene amplicons to determine the microbial communities. We normalized the data using central log ratio transformation with pseudo-counts and selected 20 microbes previously associated with CRC for analysis. Linear regression was used to assess associations between TAMs and race while adjusting for age and sex. We also examined these associations by colorectal location (distal, proximal), degree of dysplasia (high, not high), and age (< 55, 55+) using product interaction terms in our statistical models. 49% of cases were AAs, 57% were female, and 51% were less than 55 years of age. We analyzed 4 serrated polyps, 6 tubular adenoma, 16 tubulovillous adenomas, and 9 villous adenomas. 40% of the cases had high-grade dysplasia (including focal) and 51% of all lesions were from the distal colon (and rectum). We observed that AAs compared to CAs had a significantly higher microbial abundance of genus Escherichia (coef. 1.42 p=0.005), species Escherichia coli (coef. 1.38, p=0.007), and genus Shigella (coef. 1.15, p=0.02). Moreover, AAs had relatively higher TAM infiltration with these microbes in distal colorectal lesions than CAs, but there were no differences by race in the proximal colon. Finally, we observed that in comparison to older CAs, older AAs had relatively higher abundance of Escherichia (coef. 2.50; p < 0.001; p for interaction=0.056), E. coli (coef. 2.45, p=0.001; p for interaction=0.04), and Shigella (coef. 2.24, p=0.001; p for interaction=0.04), but there were no significant differences in younger patients by race. Two additional microbes, Porphyromonas (p=0.01) and Ruminococcus gnavus (p=0.02), were found in lower relative abundance in AAs vs. CAs. We identified racial differences in TAMs associated with the Enterobacteriaceae family. The stronger racial differences in TAMs observed in the older but not younger patients may reflect age-related differences in bacterial clearance. In future studies, it will be important to compare the TAMs, immune reactions with markers of tumor progression. Citation Format: Kristin Wallace, David N. Lewin, Christine Bookhout, Shaoli Sun, Brianna Bronsky, Chentha Vasu, Brenda J. Hoffman, John A. Baron, Alexander V. Alekseyenko. Racial differences in tumor-associated microbes in early colorectal carcinogenesis [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 B33.