Racial disparities in tumor microbiome in young-onset and average-onset colorectal cancer.

13 Background: The occurrence of young-onset colorectal cancer (yoCRC) is rising alarmingly, with a disproportionate incidence in Black patients as compared to White. We and others have previously shown differences in tumor microbiomes between yoCRC and average-onset colorectal cancer (aoCRC), but it is unknown if these differences contribute to racial disparities. We therefore analyzed racial differences in the intra-tumoral microbiome of CRC in young adults (<50 years). Methods: We analyzed 277 samples of histologically confirmed cases of stage I-IV CRC patients identified as either non-Hispanic Black or non-Hispanic White, who underwent surgical resection at Cleveland Clinic from year 2000-2020, who consented to a prospective biorepository. Fresh frozen specimens from the primary tumor with paired adjacent nonmalignant tissue were analyzed. The 16s rRNA gene was amplified and sequenced using V4 region primers and Illumina’s MiSeq system. Using DADA2, the quality filtered 16S rRNA amplicon reads were clustered and annotated as amplicon sequence variants (ASVs). The abundance count matrix was analyzed for alpha and beta diversity and differential abundance analysis (DAA) using Phyloseq package. Statistical tests included analysis of variance (ANOVA), permutational multivariate analysis (PERMANOVA), linear regression and Wilcoxon test. DAA and correlation analysis were controlled for false discovery rate using Benjamini Hochberg correction. Results: Differential abundance analysis highlighted key differences in the microbiome composition of Black and White patients with yoCRC. Amongst Black patients, the most prevalent taxa were Limosilactobacillus, Bacillus, Staphylococcus, Listeria and Akkermansia, whereas amongst White patients the most prevalent taxa were Enterococcus and Escherichia-Shigella (Table). Microbial profiles were also significantly different between Black patients with yoCRC and aoCRC and between White patients with yoCRC and aoCRC. At ASV level, the microbiome of Black yoCRC is more similar (R2 =0.87) to Black aoCRC, in comparison to white yoCRC (R2=0.57). Conclusions: We found significant differences between the intra-tumoral microbiome of yoCRC in the United States by race. Future epidemiologic studies and public health interventions need to account for these differences to reduce risk of yoCRC across various US populations. [Table: see text]