Pan cancer analysis of the intra-tumoral microbiome’s correlation with racial disparities.

Abstract

2519 Background: Microbiome composition can influence cancer development and is moderated by diet, hygiene, sanitation, and other environmental variables. For example, a Mediterranean diet could increase breast Lactobacillus abundance, while the gut microbiome changes dramatically with fructose intake. Recent studies have revealed correlations between microbial abundance and racial disparities in cancer. Given these reports, it is critical to examine whether environmental influences on the microbiome contribute to racial disparities in cancer incidence and prognosis. Methods: We examined the intra-tumoral microbiome in the lungs, breasts, bladder, colon, rectum, cervix, head and neck, prostate, and pancreas (n = 4,169). Raw tumor RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) and aligned to bacterial genomes. Microbial abundance was correlated to race, ethnicity, and prognostic variables (Kruskal-Wallis test or Cox regression, p< 0.05). Results: We identified several microbes correlated with racial disparities for breast and bladder cancer, two microbes for lung squamous cell carcinoma, and one microbe for colon cancer. For breast cancer, African Americans have the highest mortality rate, followed by white Americans and Asian Americans. We found that four microbes, all under the order Burkholderiales, were positively correlated with poor prognosis and were most abundant in African Americans and least abundant in Asian Americans. Therefore, increased abundance of these microbes may contribute to the observed mortality differences between races. For bladder cancer, Asian Americans have the lowest incidence and mortality rates. Seven microbes, including two Geobacillus, two Pseudomonas, and two Burkholderiales, positively correlate with good prognosis and are upregulated in Asian Americans. High Pseudomonas fluorescens abundance is positively correlated with decreased risk of death (HR: 0.57, 95% CI: 0.38-0.85). High abundance of the Burkholderiales R. pickettii (HR: 0.62, 95% CI: 0.42-0.92) and V. paradoxus (HR: 0.59, 95% CI: 0.36-0.98) also exhibit the same trend. Geobacillus and Pseudomonas are both present in food, while Burkholderiales can cause nosocomial infections and are altered by diet. Conclusions: Our study is the most comprehensive to date investigating racial differences in the intra-tumoral microbiome. Our data serve as a starting point for exploring whether environmental influence of microbial abundance contributes to racial disparities in cancer.