Colorectal Cancer In African Americans Research Articles

Abstract 7004: DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations

Abstract African Americans (AAs) have among the highest incidence and mortality rates of colorectal cancer (CRC) in the US. They present with more right-sided, microsatellite stable (MSS) tumors and are diagnosed at earlier ages than non-Hispanic Whites (NHW). While DNA methylation changes and their significance have been previously described in CRC, much less is known about the unique DNA methylation changes that occur in AA CRCs compared to NHW CRCs. In the current study, we analyzed DNA methylation changes in AA patients and compared those changes to data from NHWs. AA patients diagnosed with a MSS colorectal tumor at the Yale New Health System were included in the study. A pathologist reviewed archival slides, and selected areas from CRCs (n=160) and adjacent normal tissue (n=42) were cored (median age=59; 82 females, 78 males). DNA was bisulfite converted and analysis performed using EPIC arrays. The 450K methylation array from NHW CRCs was also analyzed for 217 CRCs and 20 normal tissues obtained from TCGA (median age=68; 103 females, 114 males). Differentially methylated regions (DMRs) with |Δβ|>0.1, FDR corrected p-value <0.05 between tumor and normal tissue were identified using SeSAMe. We identified 4881 DMRs (57% hyper- and 44% hypomethylated) between AA CRC and normal tissue. Of these, 46% were in CpG Islands, 15% in CpG Shores, 4% in CpG shelves, and 36% in open sea. Most DMRs (71%) were in promoter regions, with 18% in gene bodies, 5% in enhancer regions, and 6% in intergenic regions. Next, we performed additional DMR analysis using overlapping probes from both arrays to compare NHW with AA data. We identified 2239 DMRs between AA CRC and normal tissue compared to 4138 in NHW. Of the 2239 AA DMRs, 1419 (66%) were common with NHW DMRs, 790 (34%) were unique to AAs. There were many overlapping pathways and genes; however, the DMRs impacting these pathways differed between AA and NHW CRCs. Hypermethylation of LCK, a tyrosine kinase involved in T-cell receptor signaling, was found in 60% of AA CRCs compared to 5.9% of NHW CRCs. LCK hypermethylation leads to CD4/8 T-cell inactivation and linked to poor outcomes in lung cancer. We observed AA-specific hypermethylation of SSTR1 in 57.2% of AA CRCs compared to 27.6% of NHW CRCs. Somatostasin (SST) suppresses tumor growth by regulating certain factors involved in cell proliferation. Hypermethylation of SSTR1 has been associated with various malignancies including gastric cancer. Lastly, promoter hypermethylation of 3 protocadherin genes was found in 65.1% of AAs compared to 33.1% NHWs. Protocadherins regulate WNT signaling and hypermethylation is associated with poor outcomes in multiple cancers. Taken together, these results show AA-specific CRC methylation changes compared with NHW CRCs. Further work is warranted to investigate the potential functional and clinical implications of these methylation alterations, some of which may represent therapeutic targets and biomarkers. Citation Format: Seeta Rajpara, David N. Buckley, Rosa Xicola, Reger Mikaeel, Mary K. Yagle, Baris Kerimoglu, Curtis Thorne, Dante A. Bellomo, Megha Padi, Xavier Llor, Nathan Ellis, Bodour Salhia. DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7004.

Abstract 6180: Tumor microenvironment phenotypes predict recurrence in African Americans diagnosed with colorectal cancer: A comparative study of manual grading with digital pathology

Abstract African Americans face a higher rate of colorectal cancer (CRC) incidence and mortality compared to other ethnicities. Identifying key prognostic factors is essential for better outcomes in this group. This study focused on the prognostic value of stromal grading in the tumor microenvironment (TME) of African American CRC patients, using both manual grading and digital pathology. A retrospective analysis of CRC cases in African Americans was conducted. Two cohorts were established: a control cohort (patients without recurrence) and a recurrence cohort (patients with recurrence). Stromal grading was performed manually, categorizing tumors into Grade 1 (low risk), Grade 2 (moderate risk), and Grade 3 (high risk), and we also quantified the TME percentages by digital pathology: myxoid, collagen, immune and tumor. In the control cohort (N=40), stromal grading identified 30 Grade 1, 7 Grade 2, and 3 Grade 3 cases. Conversely, the recurrence cohort (N=17) demonstrated a starkly different distribution, with 1 Grade 1, 3 Grade 2, and 13 Grade 3 cases. The Chi-square statistic was notably significant (p<0.0001), indicating a strong association between higher stromal grades and the likelihood of recurrence. By unpaired t-test, high myxoid stroma (p<0.0001), low collagen (p<0.0001), and low tumor (p=0.0002) by digital pathology were associated with recurrence. TME phenotypes are a significant prognostic and recurrence indicator in African American patients with CRC. The marked difference in stromal grades and digital pathology features between the control and recurrence cohorts suggests that higher stromal grades, along with higher myxoid, lower collagen and lower tumor percentages are associated with an increased risk of recurrence. These findings underscore the need for tailored therapeutic strategies and more vigilant surveillance in African American patients exhibiting high-risk TME phenotypes. The efficacy of manual and digital pathology evaluation of the TME also warrants further exploration to enhance prognostic accuracy and treatment personalization. Citation Format: Dongling Wu, Rong Xia, Mouyed Alawad, Lili Lee, Tamas Gonda, Wenqing Cao, Sean Hacking. Tumor microenvironment phenotypes predict recurrence in African Americans diagnosed with colorectal cancer: A comparative study of manual grading with digital pathology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6180.

Abstract C060: DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations

Abstract African Americans (AAs) have among the highest incidence and mortality rates of colorectal cancer (CRC) in the US. They present with more right-sided, microsatellite stable tumors and are diagnosed at earlier ages than non-Hispanic Whites (NHW). While DNA methylation changes and their significance have been previously described in CRC, much less is known about the unique DNA methylation changes that occur in AA CRCs compared to NHW CRCs. In the current study, we analyzed DNA methylation changes in AA patients and compared those changes to data from NHWs. AA patients diagnosed with a microsatellite-stable colorectal tumor at the Yale New Health System were included in the study. A pathologist reviewed archival slides, and selected areas from tumor (n=160) and adjacent normal tissue (n=42) were cored. The median age of patients was 59 from 82 females and 78 males. Extracted DNA was bisulfite converted and tested using EPIC arrays. DNA methylation (450K) from NHW CRCs was also analyzed for 217 CRCs and 20 normal tissues obtained from TCGA (median age=70; 114 males, 103 females). Differentially methylated regions (DMRs) with |Db|>0.1, FDR corrected p-value <0.05 between tumor and normal tissue were identified using SeSAMe. We identified 4881 DMRs (57% hyper- and 44% hypomethylated) between AA CRC and normal tissue. Of these, 46% were in CpG Islands, 15% in CpG Shores, 4% in CpG shelves, and 36% in open sea. Most DMRs (71%) were in promoter regions, compared with 18% in gene bodies, 5% in enhancer regions, and 6% in intergenic regions. Next, we performed an additional DMR analysis using overlapping probes from the 450K and EPIC arrays to compare TCGA NHW with Yale AA data. We identified 2290 DMRs between AA CRC and normal tissue compared to 4657 in NHW. Of the 2290 AA DMRs, 1405 (61%) were common with NHW DMRs, 885 (39%) were unique to AAs. There were many overlapping pathways and genes involving metabolic functions, DNA damage response, immune response, and WNT signaling. However, the DMRs impacting these pathways differed between AA and NHW CRCs. Several AA-specific DMRs were associated with immune response and included LCK and GPSM3 genes. Hypermethylation of LCK, a tyrosine kinase involved in T-cell receptor signaling, was found in 60% of AA CRCs compared to 8% of NHW CRCs. LCK hypermethylation leads to CD4/8 T-cell inactivation and is linked to poor outcomes in lung cancer. We also observed AA-specific hypermethylation of GPSM3 in 60% of AA CRCs compared to 18% of NHW CRCs. GPSM3 is associated with CD4/8 T-cell infiltration. Lastly, promoter hypermethylation of 6 protocadherin genes was found in 59% of AAs compared to 20% NHWs. Protocadherins play a role in regulating WNT signaling and hypermethylation has been associated with poor outcomes in multiple cancers. Taken together, these results show AA-specific CRC methylation changes compared with NHW CRCs. Further work is warranted to investigate the potential functional and clinical implications of these methylation alterations, some of which may represent therapeutic targets and biomarkers. Citation Format: David N. Buckley, Rosa Xicola, Mikaeel Reger, Mary K. Yagle, Baris Kerimoglu, Curtis Thorne, Dante Bellomo, Megha Padi, Xavier Llor, Nathan Ellis, Bodour Salhia. DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C060.

Microbiome diversity in African American, European American, and Egyptian colorectal cancer patients

PurposeAlthough there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients. Patients and methodsCRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA sequencing. Differential microbial abundance, diversity, and metabolic pathways were identified using linear discriminant analysis (LDA) effect size analyses. Additionally, we compared these profiles with our previously published microbiome data derived from Kenyan CRC patients. ResultsDifferential microbiome analysis of CRCs across all racial/ethnic groups showed dysbiosis. There were high abundances of Herbaspirillum and Staphylococcus in CRCs of Egyptians, Leptotrichia in CRCs of AAs, Flexspiria and Streptococcus in CRCs of EAs, and Akkermansia muciniphila and Prevotella nigrescens in CRCs of Kenyans (LDA score >4, adj. p-value <0.05). Functional analyses showed distinct microbial metabolic pathways in CRCs compared to normal tissues within the racial/ethnic groups. Egyptian CRCs, compared to normal tissues, showed lower l-methionine biosynthesis and higher galactose degradation pathways. ConclusionsOur findings showed altered mucosa-associated microbiome profiles of CRCs and their metabolic pathways across racial/ethnic groups. These findings provide a basis for future studies to link racial/ethnic microbiome differences with distinct clinical behaviors in CRC.

Abstract 1906: MSH3: An underestimated DNA MMR gene in colorectal carcinogenesis and its potential role in disparity

Abstract Background: Unique mutations in cancer genes have been found in different races including African Americans (AA) population. Maintenance of proficient mismatch repair genes is important in colorectal cancer. Among them, MSH3 is found to be more important in colorectal cancer in AA particularly as its alterations associate with EMAST phenotype that has poor prognosis. However, there are regional variations in the classification and criteria used to determine the pathogenicity of these mutations particularly in AA due to their high genomic diversity. Aim: To analyze unique and novel MSH3 mutations using specific in-silico prediction tools and to validate their biological significances in AA-CRC. Results: In this study, we validated our targeted exome sequencing data of MSH3 mutations in AA and Caucasians (CA) CRC samples. A cost effective in-silico approach was employed to narrow down most significant MSH3 mutations. Interestingly, we and found six non-synonymous novel, pathogenic mutations in MSH3 gene (c.G1237A, c.C2759T, c.G1397A, c.G2926A, c.C3028T, c.G3241A) correspond to MSH3 protein (E413K; S466N; S920F; E976K; H1010Y; E1081K), in AA than CA samples. Also, we observed loss or gain of different chemical bonding patterns (hydrogen, ionic, hydrophobic, and di-sulfide bonding) between wild type and mutant MSH3 protein. Interestingly, some of these mutations were within the ATPase site while others are in MSH3-MSH2 interacting domains. Furthermore, Molecular Dynamics Simulation (MDS) of these six mutants of MSH3 proteins showed an overall effect on MSH3 protein stability especially in MSH3-MSH2 interaction compared to wild type MSH3 protein.Conclusion: Our data showed that, six MSH3 non-synonymous mutations are deleterious as they affect important sites within MSH3-MSH2 interactive and ATPase domain. Assessing the real frequency of these mutations in large cohort and their specific effect on function may shed light on EMAST phenotype, high prevalence, and overall poor prognosis in the AA population. In vitro functional assays using CRISPR-Cas9 knock-in and in vivo studies are underway to mimic these mutations. Citation Format: Mudasir Rashid, Rumaisa Rashid, Minoru Koi, John M. Carethers, Hassan Brim, Hassan Ashktorab. MSH3: An underestimated DNA MMR gene in colorectal carcinogenesis and its potential role in disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1906.

Abstract 1907: Unique and novel deleterious MSH6 mutation among African American patients with colorectal cancer

Abstract Background: Colorectal cancer (CRC) incidence and mortality in African Americans (AA) is higher compared to Caucasians (CAU). It has also been reported that the disparity is due to differences in the mutation spectrum particularly germline mutations in the DNA mismatch repair (MMR) genes (such as hMSH6). Aim: We aimed to determine MSH6 mutation profile in AAs with CRC. Methods: We performed RNA sequencing in 8 paired CRC samples (AA, n=4 and CAU, n=4) to identify the unique transcript and novel pathogenic mutation in AA compared to CAU by comparing CRC matched to corresponding normal epithelia. In silico analysis of TCGA COAD RNA sequencing data was performed. Results: We found non-synonymous germline mutations (p.G1139S) in exon 5 of MSH6 gene (one of the MMR genes) in AA CRC samples. Interestingly, this mutation is present in the active site of ATP binding (1135 to 11442 residue) motif of MSH6 protein. In silico analysis was used to determine the novelty and pathogenicity of this mutation by comparison to various publicly available databases. Also, the deleterious effect of p.G1139S missense mutation on the structure of MSH6 protein revealed that p.G1139S is destabilizing MSH6 protein. Based on Ramachandran plot analysis, we found lot of clash and outliers in the mutant type compared to wild type MSH6 protein. Structural analysis revealed that serine substitution results in a wide ATP binding site compared to glycine present in wild-type MSH6. In addition, we found a loss of hydrogen bonding or gain of ionic interaction between wild-type and mutant MSH6 protein. Conclusion: Based on our in silico analysis, the deleterious effect of the detected missense mutation in the active site of ATP binding motif of MSH6 affects the structure and function of MSH6. This may result in the accumulation of mono-, or di-nucleotide repeats instability in the genome, leading to genomic alterations that associate with carcinogenesis in African American CRC patients. Citation Format: Mudasir Rashid, Rumaisa Rashid, Sudhir Varma, Zaki Sherif, John Carethers, Hassan Brim, Hassan Ashktorab. Unique and novel deleterious MSH6 mutation among African American patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1907.

Abstract 725: Biomarkers of circulating vitamin D status and expression of tumor molecular markers Ki67, p53, and COX2 among colorectal cancer cases in the Southern Community Cohort Study

Abstract Introduction: Epidemiologic studies and controlled trials provide evidence that higher 25-hydroxyvitaminD is associated with improved survival in colorectal cancer (CRC), although there are limited data in African Americans (AAs), who are at greater risk for CRC mortality and vitamin D deficiency. Herein, we report associations between vitamin D serum biomarkers collected at cohort entry up to 15 years prior to CRC onset and CRC tumor subtypes defined by high expression of tumor markers (Ki67, p53, and COX2) that represent cellular processes (proliferation, apoptosis, and inflammation) affected by vitamin D. Importantly, higher expression of these markers reflects greater risk for metastasis and CRC-specific mortality. Methods: Data arise from the Southern Community Cohort Study, a cohort from the southeastern United States where the majority of participants are AA. Incident CRC cases with tumor sample were analyzed (n=104). Expression of cellular Ki67, p53, and COX2 (% positivity) were measured and categorized by literature-defined high vs. low cut-points (20%, 10%, and 20%, respectively). Logistic models adjusted for age, race, and sex were used to measure associations between vitamin D biomarkers: 25-hydroxyvitaminD, vitamin D binding protein (VDBP), and calculated free 25-hydroxyvitaminD (vitamin D not bound by VDBP) and the odds of a more aggressive tumor subtype, defined by higher cellular expression. Associations were assessed in the full sample and the subsample of AAs (n=70). Results: There were 52 tumors with high Ki67 expression, 37 with high p53, and 50 with high COX2. Fifteen tumors had high expression of all three markers. Cases were 55.8±0.4 (mean±SE) years at enrollment (range 40-79). The median 25-hydroxyvitaminD was lower in cases with high p53 expressing tumors compared to low expression (13.5 vs. 18.0 ng/mL, respectively, p = .03). Median values for other biomarkers were similar by tumor subtype (p &amp;gt .05). 25-hydroxyvitaminD was not associated with having a tumor with high Ki67 expression (odds ratio (OR) per 1 SD increase [95% CI] = 1.29 [0.85-1.95], p-trend = .23), high p53 expression (0.80 [0.52-1.23], p-trend = .30), or high COX2 expression (1.29 [0.83-2.00], p = .25). We observed null associations for VDBP, and free 25-hydroxyvitaminD with all tumor subtypes. Results were similar in AAs, although higher VDBP was associated with lower odds of high Ki67 tumors (0.45 [0.21-0.97], p-trend = .04 per 1 SD increase). Conclusion: In this sample of predominantly AA CRC cases, we observed no association between vitamin D biomarkers in stored serum and subsequent more aggressive CRC molecular subtypes. More work is needed to characterize the relationship between vitamin D and expression of CRC tumor markers, which may help clarify the protective role of maintaining adequate vitamin D levels in association with CRC. Citation Format: Thomas Lawler, Timothy Su, Qiuyin Cai, Mark Steinwandel, Wei Zheng, William J. Blot, Shaneda Warren Andersen. Biomarkers of circulating vitamin D status and expression of tumor molecular markers Ki67, p53, and COX2 among colorectal cancer cases in the Southern Community Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 725.

Abstract PO-180: Synergistic interplay between genetic characteristics of glucose homeostasis and long-term exposure to cigarette smoking in development of African American colorectal cancer

Abstract Background: Colorectal cancer (CRC) is the leading cause of cancer diagnosis and death in women in the United States and other westernized countries and approximately 90% of new cases and deaths occur in women 50 years old and older. African American (AA) women have the highest CRC incidence and mortality rates among all races/ethnic female groups. Also, CRC is the third most common cancer diagnosis and cause of cancer deaths in AA women. Insulin resistance (IR) or glucose intolerance is a critical biologic mechanism for the development of CRC owing to obesity in postmenopausal women. Whereas IR and excessive adiposity are more prevalent in AA women than in white women, AA women are under-represented in genome-wide studies for systemic regulation of IR and the association with CRC risk. Methods: Having examined 780 genome-wide IR single-nucleotide polymorphisms (SNPs) available in the Women's Health Initiative Database for Genotypes and Phenotypes (WHI dbGaP) SNP Health Association Resource (SHARe) among 4,692 AA women, we tested for a causal inference between genetically elevated IR and CRC risk in a Mendelian randomization (MR) framework. Further, by incorporating 35 CRC-associated lifestyle factors, we established a prediction model on the basis of gene–environment interactions to generate risk profiles for CRC with the most influential genetic and lifestyle factors and eventually estimated their combined and joint effects on CRC risk. Results: In the pooled MR analysis, the genetically elevated IR was associated with 9 times increased risk for CRC. By addressing the variation of individual SNPs in CRC risk in the prediction model, we detected 4 fasting glucose–specific SNPs in GCK, PCSK1, and MTNR1B and 4 lifestyles, including smoking, aging, prolonged lifetime exposure to endogenous estrogen, and high fat intake, as the most predictive markers for CRC risk. Our joint test for those risk genotypes and lifestyles with smoking revealed the synergistically increased CRC risk, more substantially in women with longer-term exposure to cigarette smoking. Conclusion: Our findings may improve CRC prediction ability among medically under-represented AA women and highlight genetically informed preventive interventions (e.g., smoking cessation; CRC screening to longer-term smokers) for those women at high risk with risk genotypes and behavioral patterns. Citation Format: Su Yon Jung. Synergistic interplay between genetic characteristics of glucose homeostasis and long-term exposure to cigarette smoking in development of African American colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-180.

Abstract 2413: POLE gene mutations in African Americans colorectal cancer

Abstract Background: Most focus in genetic instability in colon carcinogenic transformation was on DNA Mismatch Repair (MMR) genes alterations as they relate to the microsatellite instability phenotype. However, POLE gene mutations can also be instrumental in triggering genetic instability, at even higher magnitude of genome mutation rate. Aim: To assess POLE gene mutations in African Americans with colorectal cancer (CRC). Methods: Data from Whole exome sequencing of 12 CRC African American tumors was searched to scan POLE gene mutations. All detected mutations were checked in tumors and matched normal. The detected mutations were validated in a second set of samples that were sequenced using POLE gene targeted sequencing. Detected and validated mutations were checked in available databases such as COSMIC and dbSNP to determine novel mutations in our population that is at high risk of aggressive CRC. Results: Six out of 12 patients (50%) displayed mutations in POLE gene. There were 41 detected mutations, 11 are novel mutations and 15 are amino-acid changing. Nine of these were non-synonymous and predicted to have deleterious effects. All these mutations were validated using targeted sequencing. In comparison to DNA MMR, POLE gene has four folds more mutations than MSH2gne (10 mutations and MSH6 (11 mutations and two fold more than MSH3 gene (20 mutations) in the same set of 12 cancer/matched normals. The POLE mutations heterozygous/homozygous status was overall similar in normal and matched normal. However, most of the mutations were homozygous. Conclusion: POLE gene mutations are increasingly recognized as another important element in genetic instability. Our data shows that mutations affecting this gene are likely more significant than those affecting DNA MMR genes. Moreover, POLE mutations might be more consequential, especially those affecting its exonuclease domain of polymerase epsilon, proofreading catalytic subunit. Microsatellite-stable, hypermutated CRCs might need to be explored for POLE gene mutations to track the origin of high mutation rates. Citation Format: Hassan Brim, Babak Shokrani, Hamed Azimi, Sudhir Varma, Edward Lee, Hassan Ashktorab. POLE gene mutations in African Americans colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2413.

Abstract 3342: The colorectal cancer associated microbe Odoribacter splanchnicus produces genotoxic hydrogen sulfide via cysteine metabolism

Abstract The proinflammatory and genotoxic properties of hydrogen sulfide (H2S) have been implicated as an environmental trigger of colonic disease. Recent evidence links sulfidogenic bacteria capable of metabolizing organic sulfur substrates, like dietary sulfur amino acids and taurine conjugated bile acids, with increased colorectal cancer (CRC) and colitis risk as a consequence of a “western” type diet. Our previous work demonstrates that the sulfidogenic bacterium, Odoribacter splanchnicus, is a significant indicator of CRC in African Americans who are at higher risk of CRC incidence and death than other races and ethnicities in the United States. This observation has been corroborated by several recent studies that observed O. splanchnicus to be associated with CRC and colitis-induced CRC. While previous work has reported that O. splanchnicus may be sulfidogenic, its method of H2S production has yet to be characterized. Production of H2S by O. splanchnicus was confirmed in vitro using sulfide indole and motility media, and varying sulfur substrates. A predictive metabolic analysis of 74 O. splanchnicus metagenomes taken from publicly available CRC cohorts did not reveal complete pathways commonly associated with H2S production, however genes for a polar amino acid transporter were revealed. Therefore, a genomic analysis was performed revealing that O. splanchnicus harbors the sulfidogenic genes tryptophanase (tnaA) and cystathionine-β-synthase. The enzyme TnaA has been previously shown in Eschericia coli to produce indole or H2S from tryptophan or cysteine, respectively. However, the E. coli amino acid sequence shares only 44.85% identity with that from O. splanchnicus, thus heterologous protein expression of recombinant tnaA was performed to determine enzyme functionality. Enzyme kinetics and pH optimum were obtained using the spectrophotometric BiCl3 assay, which turns black in presence of H2S. Functional analysis of recombinant purified TnaA revealed bifunctionality of the enzyme with positive tryptophanase and cysteine desulfhydrase activity with differing substrates. Cysteine desulfhydrase activity resulted in consumption of L-cysteine with subsequent production of H2S and pyruvate. Thus, TnaA is a functional enzyme that warrants further evaluation as possibly relating to sulfidogenic O. splanchnicus being linked to CRC and colitis-associated CRC. Citation Format: Patricia G. Wolf, Vladimir Kolosslov, Zhichao Zhou, Lindsey Ly, Heidi Doden, Saravanan Devendran, Adam M. Breister, Luke Lucio, Paige Polak, Sarah Matatov, Karthik Anantharaman, Jason M. Ridlon, Rex Gaskins. The colorectal cancer associated microbe Odoribacter splanchnicus produces genotoxic hydrogen sulfide via cysteine metabolism [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3342.

Abstract C036: Cohesins and colorectal cancer (CRC): Modulation of CRC stem cells and chemoresistance by STAG1 with race-specific implications

Abstract Despite advances in treatment and early detective measures for colorectal cancer (CRC), African-Americans (AAs) suffer disproportionately from CRC (~25% higher incidence and ~50% higher mortality) than Caucasians. Furthermore, AAs tend to receive earlier diagnoses in CRC and AA CRCs with high-grade differentiation were 3xs more likely to die within 5 yrs post-surgery as compared to whites (Alexander et al., Cancer 2005). The underlying mechanisms behind this more aggressive disease in AAs are poorly understood. Tomassati and Vogelstein postulate stem cell division correlates with risk of cancer (Science 2015). Addressing disease progression/aggressiveness, CRC stem cell markers are linked to chemoresistance; stem cell markers LGR5 and ALDH1a are established CRC stem cell markers. We have shown that the cohesin family member STAG1, a chromatin remodeler, is lost in the colonic epithelium of patients with premalignant lesions and AAs had a more profound loss (Cancer Prev Research 2016) through AA-specific STAG1 SNPs (Neoplasia 2018) and hypothesize that STAG1 loss is associated with poorer prognosis. Therefore, we wanted to investigate if STAG1 loss may lead to CRC stem cell induction as a potential mechanism of the racial disparities in CRC. RNA from rectal biopsies from 100 patients undergoing screening colonoscopies was processed for real-time PCR for CRC stem cell markers LGR5 and ALDH1a, as well as STAG1. To determine chemoresistance, STAG1 siRNA was transfected in CRC cell line HT29 and a CRISPR transfection of STAG1 SNP rs34149860 (found only in AAs) was transfected in CRC cell line RKO (possessing wildtype to SNP). Cell were treated with 5-FU and oxaliplatin and subjected to Annexin V Assay. Real-time PCR and analysis of STAG1 and CRC stem cell markers were performed for causation. AAs harboring neoplasias displayed a more robust loss of STAG1 mRNA (~50%, p&amp;lt;0.007) vs Caucasians with neoplasias (~25%, p=0.1). In regard to CRC stem cell markers, AAs with adenomas showed a stronger increase of LGR5 (67%, p=0.14), and ALDH1a (73%, p&amp;lt;0.007) vs Caucasians with neoplasias (LGR5 increased 59%, p=0.2; ALDH1a increased ~47%, p&amp;lt;0.05). HT29 cells transfected with STAG1 siRNA showed 30% less apoptotic response to 5-FU vs scramble vector and a marked 74% less response with oxaliplatin. CRIPSR SNP transfection in RKO showed similar effects, with a 2-fold less apoptotic response to 5-FU and &amp;gt;90% less response to oxaliplatin. PCR showed RKO STAG1-SNP transfected cells displayed a loss of STAG1(~40%, p&amp;lt;0.05) and an upregulation of LGR5 (~50%, p&amp;lt;0.05) and ALDH1a (~30%, p&amp;lt;0.05). This shows, for the first time, that STAG1 loss is implicated in colon carcinogenesis through potentiation of cancer stem cells through early carcinogenesis/initiation as well as disease progression and aggressiveness as shown through chemoresistance. Our work provides a potential mechanism in CRC, thus providing a biomarker for cancer screening and therapeutics that could mitigate the racial disparity of CRC in AAs. Citation Format: Mart Dela Cruz, Caroline Zaworski, Somenath Datta, Sanjib Chowdhury, Hemant K. Roy. Cohesins and colorectal cancer (CRC): Modulation of CRC stem cells and chemoresistance by STAG1 with race-specific implications [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C036.

Abstract D058: Truth Talking Tour: Women’s sexuality after cancer

Abstract Background Due in part to advances in diagnosis, treatment, and early detection the number of cancer survivors in the United States is growing with an estimated 16.9 million cancer survivors and projected to increase to 21.7 million by 2029. Among the current survivor population, 8.8 million are female. Disparities in survivorship care exist, including poorer health outcomes related to sexual health impairment and stress from financial toxicity of cancer. A larger proportion of African American (AA) breast and colorectal cancer survivors experience issues related to lack of resources and information related to sexuality after cancer. The impact of breast cancer on sexuality among women is often examined, yet limited research has been conducted with AA survivors of other cancers such as colorectal cancer. Cultural considerations such as religion/spirituality and body image should be included in interventions addressing psychosocial needs of female AA cancer survivors. The Truth Talking Tour: Women’s Sexuality after Cancer was created by community stakeholders to give women a safe space to talk about sexuality and cancer. Methods The University of Illinois Patient Brigade convened a cohort of patient-centered outcomes research (PCOR) “ready” advocates to engage in desired training, guide center leadership activities and inform research tools/dissemination strategies that can inform PCOR. The Truth Talking Tour was developed by Patient Brigade cancer advocacy leaders for women in any stage of their cancer survivorship and included active participation from community members and health care providers. Results Thirty-nine women attended the workshop held in Spring 2019 at a community location on the Southside of Chicago. All survey respondents were AA, age range from 40 to 68, age at cancer diagnosis ranged from 25 to 63. Pre/post survey was conducted to explore impact of the convening on knowledge, priorities and needs of AA female cancer survivors. Results demonstrated that AA female cancer survivors see convening with other survivors and clinician experts as important and missing from current efforts. Results also showed that women with a cancer diagnosis are physically and psychologically challenged in their fight against cancer and face challenges with sexual identities currently unmet by survivorship care plans. Priority areas that emerged included lack of resources, lack of knowledge of providers, and lack of culturally tailored interventions for AA female cancer survivors. Conclusions The Truth Talking Tour survey data demonstrated additional research is needed to assess the needs of AA female cancer survivors impacted by lack of data on sexuality after cancer. Feasibility of the convening demonstrated that community-academic partnerships rooted in dialogue and data may be a great way to inform future interventions to improve sexuality after cancer among AA women. The community stakeholders leading the Truth Talking Tour have planned additional tours in the south, west and east coast. Citation Format: Candace Henley, Joanne Glenn, Vida Henderson, Jacqueline Kanoon, Melissa Simon, Susan Hong, Karriem S Watson. Truth Talking Tour: Women’s sexuality after cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D058.

Abstract C118: Tumor immune response in colon cancer African American patients and its role in cancer disparities

Abstract Introduction: Colorectal cancer (CRC) is the third most common cancer among African Americans (AA) and when compared to Caucasian Americans (CA), they present more advanced CRC disease and lower survival rates. Our previous findings suggest that this may be related to the differential expression in genes linked to cell recruitment and immune response. Therefore, we aimed to investigate the cellular antitumor activity and mutational profile of colon tumors from AAs. We also examined the secretion of cytokines characteristic of immune responses by different effector T helper cells (Th) subsets in AA and CA patients, as well as cell lines, to see if these differences play a role in the health disparities observed between these populations. Lastly, we observed the expression of the Program Death Ligand 1 (PD-L1) in response to the cytokines IL-17A and TNF-α in a microsatellite-unstable (MSI) AA and a microsatellite-stable (MSS) CA colon cancer cell line. Methods: Using IHC, we evaluated the cell recruitment and activation of T and natural killer cells in AA tumors. For mutational analysis, we utilized the TruSight Tumor 170 RUO kit (Illumina). ELISA assays (RayBiotech) were used to examine the secretion of cytokines linked to Th subsets (Th1, Th2, Th17) and inflammation in plasma from the AA and CA CRC patients, as well as in supernatants from the AA and CA colon cancer cell lines. Western blots were used to observe the expression of PD-L1 in the in vitro models. Results: ELISAs of plasma of CA and AA patients revealed a differential Th cytokines production patterns between early-stages (I, II) and late-stage (III) disease. The MSI AA cell line showed an increase on PD-L1 protein expression in response to IL-17A and TNF-α with an additive effect when combined in equal concentrations. Lastly, the mutational sequencing allowed us to further investigate the potential alterations that are responsible for the differences that we observed in gene expression between AAs and CAs in our RNA and cytokine expression profiling. Conclusions: Our results indicate that the immune profiles of AA patients differ from CA in terms of cytokines' production; AAs expressed elevated IL-17A, whereas CA expressed elevated IFN-γ, the latter indicative of Th1 immunity that has a more favorable prognosis. As such, these differences could be used as biomarkers and to guide therapeutic strategy for these populations. The mutational sequencing will help us to elucidate the impaired tumor immune response in AAs with colon cancer when compared to CAs that we observed in terms of cell recruitment and cytokine secretion in our previous findings. Importantly, our data indicate that IL-17A and TNF-α promote the protein production of PD-L1 in an MSI AA cell line, which may result in the impairment of T cells' antitumor activity. Taken together, the differences in the immunologic profiles in AA when compared to CA suggest a deficiency of the appropriate immune defense mechanisms in this population that may contribute to the cancer health disparities among CRC patients. Citation Format: Jenny E. Paredes, Ping Ji, Jone Garai, Marzia Spagnardi, Maria Munoz-Sagastibelza, Sayed Imtiaz, Gayle Mendez, Mubarak Akadri, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Ellen Li, Jovanny Zabaleta, Laura Martello-Rooney, Jennie Williams. Tumor immune response in colon cancer African American patients and its role in cancer disparities [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C118.

Decreased copy-neutral loss of heterozygosity in African American colorectal cancers.

Despite improvements over the past 20 years, African Americans continue to have the highest incidence and mortality rates of colorectal cancer (CRC) in the United States. While previous studies have found that copy number variations (CNVs) occur at similar frequency in African American and White CRCs, copy-neutral loss of heterozygosity (cnLOH) has not been investigated. In the present study, we used publicly available data from The Cancer Genome Atlas (TCGA) as well as data from an African American CRC cohort, the Chicago Colorectal Cancer Consortium (CCCC), to compare frequencies of CNVs and cnLOH events in CRCs in the two racial groups. Using genotype microarray data, we analyzed large-scale CNV and cnLOH events from 166 microsatellite stable CRCs-31 and 39 African American CRCs from TCGA and the CCCC, respectively, and 96 White CRCs from TCGA. As reported previously, the frequencies of CNVs were similar between African American and White CRCs; however, there was a significantly lower frequency of cnLOH events in African American CRCs compared to White CRCs, even after adjusting for demographic and clinical covariates. Although larger differences for chromosome 18 were observed, a lower frequency of cnLOH events in African American CRCs was observed for nearly all chromosomes. These results suggest that mechanistic differences, including differences in the frequency of cnLOH, could contribute to clinicopathological disparities between African Americans and Whites. Additionally, we observed a previously uncharacterized phenomenon we refer to as small interstitial cnLOH, in which segments of chromosomes from 1 to 5 Mb long were affected by cnLOH.

199 Clinical and Molecular Characteristics of Early-Onset Colorectal Cancer Across Various Ethnicities

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in the United States. Guidelines from the American Cancer Society recommend CRC screening at 45 years of age in average-risk patient populations. Previous studies have shown an increase in incidence of CRC in African Americans (AAs) less than 50 years of age. We aimed to examine the disease characteristics of patients with early-onset CRC (EOCRC) across different races. METHODS: A retrospective cross-sectional study was performed using our electronic pathology database. All patients diagnosed with CRC between January 2012 and September 2018 were included. Data regarding patient demographics, co-morbid conditions and patient presentation was noted. In addition to information regarding the location, staging and molecular features of CRC. RESULTS: A total of 627 patients with CRC were identified. Out of these, 117 (18.6%) were younger than 50 years of age (EOCRC). Table 1 compares the baseline characteristics of patients across different races. The mean age of onset of CRC was significantly lower in Hispanics compared to Caucasians [56.6 years vs 61.6 years, P value = 0.0002] and AAs [56.6 years vs 60.2 years, P value = 0.01]. The clinical and molecular features of CRC across different racial groups are summarized in Table 2. The proportion of patients with early-onset CRC was higher in Hispanics as compared to Caucasians (27.9% vs 16.0%, P value = 0.004) and AAs (27.9% vs 16.9%, P = 0.03). On a multivariate analysis after adjusting for confounders, the proportion of Hispanics with early-onset CRC was significantly higher as compared to Caucasians [OR: 2.2, (95% CI 1.3–3.7), P value = 0.003]. Hispanics were less likely to harbor BRAF mutation as compared to Caucasians (5.1% vs 13.1%, P-value: 0.05), while Hispanics were more likely to have mutations in MSH-6 (100% vs 91.3%, P-value: 0.01) and MSH-2 (100% vs 94.2%, P-value = 0.05) as compared to AAs. CONCLUSION: Our study shows that proportion of patients with early-onset CRC is higher in Hispanics as compared to Caucasians and AAs. In addition, there are unique molecular features specific to CRC across various racial groups. Our findings raise concerns that there might be knowledge gaps regarding early-onset CRC amongst minority populations. Further large multi-center studies are needed to better understand the unique clinical and molecular characteristics in early-onset CRC in minority populations.

Distribution of colorectal cancer in young African Americans: implications for the choice of screening test

We recently reported on a left-sided predominance of colorectal cancers in the young (under age 50). Given the predilection of young African Americans for the disease, we wondered if there may be a difference in the biology of colorectal carcinogenesis between this group and Caucasians. Compare the distribution of colorectal cancer in African American patients and Caucasians under age 50, and describe implications for screening in these groups. Colorectal cancer patients diagnosed under the age of 50 between the years 2000 and 2016. All races other than African American and Caucasian and all patients with hereditary colon cancer or inflammatory bowel disease were excluded. race, age at diagnosis (5 subgroups: < 20, 20-29, 30-39, 40-44, and 45-49years) and cancer location; right (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure), left (descending colon and sigmoid colon), or rectal. 759 patients were included; 695 (91.6%) were Caucasian and 64 (8.4%) were African American. Most cases were diagnosed between ages 40 and 49 (African American = 75%, Caucasian = 69.5%). Rectal cancer was most common in both races, although significantly more common in Caucasian than in African American patients (64.2% vs 39.1%). Right colon cancer was more commonly found in African Americans (37.5%) compared with Caucasians (18%) (p = 0.0002). The ratio of rectal to right-sided colon cancer in African Americans was 1:1 compared with 3.6:1 in Caucasians. Relatively low number of African American patients CONCLUSION: The high rate of right-sided cancer in young African American patients means that they should be screened with colonoscopy. The increased incidence of right-sided cancers may represent a different biology of carcinogenesis in African Americans and deserves further study.

Clinical and Genetic Factors to Inform Reducing Colorectal Cancer Disparitites in African Americans.

Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 140,250 cases and 50,630 deaths for 2018. Prevention of CRC through screening is effective. Among categorized races in the U.S., African Americans (AAs) show the highest incidence and death rates per 100,000 when compared to Non-Hispanic Whites (NHWs), American Indian/Alaskan Natives, Hispanics, and Asian/Pacific Islanders, with an overall AA:NHW ratio of 1.13 for incidence and 1.32 for mortality (2010-2014, seer.cancer.gov). The disparity for CRC incidence and worsened mortality among AAs is likely multifactorial and includes environmental (e.g., diet and intestinal microbiome composition, prevalence of obesity, use of aspirin, alcohol, and tobacco use), societal (e.g., socioeconomic status, insurance and access to care, and screening uptake and behaviors), and genetic (e.g., somatic driver mutations, race-specific variants in genes, and inflammation and immunological factors). Some of these parameters have been investigated, and interventions that address specific parameters have proven to be effective in lowering the disparity. For instance, there is strong evidence raising screening utilization rates among AAs to that of NHWs reduces CRC incidence to that of NHWs. Reducing the age to commence CRC screening in AA patients may further address incidence disparity, due to the earlier age onset of CRC. Identified genetic and epigenetic changes such as reduced MLH1 hypermethylation frequency, presence of inflammation-associated microsatellite alterations, and unique driver gene mutations (FLCN and EPHA6) among AA CRCs will afford more precise approaches toward CRC care, including the use of 5-fluorouracil and anti-PD-1.

Adenoma Detection Rates in Patients in the 40-49 Year Age Group Across Different Ethnicities: Presidential Poster Award

Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer related deaths in United States. Recent guidelines from the American Cancer Society (ACS) recommend starting CRC screening at 45 years in average-risk patient population in United States. Previous studies have shown an increase in incidence of CRC in African Americans less than 50 years of age. Despite this, there is limited evidence about prevalence of adenomatous polyps in this age group. We aimed to examine the prevalence of adenomas in 40 to 49 years old patients without any family history (FH) of CRC or polyps across different races. Methods: A retrospective cross sectional study was performed using our electronic endoscopy database. Study subjects included all 40 to 49-year-old patients without any FH of CRC undergoing their index colonoscopy at our tertiary care academic institution from January 1, 2010 to September 30, 2017. Exclusion criteria included patients who underwent colonoscopy for overt gastrointestinal bleeding, inflammatory bowel disease, patients who had previous colonoscopies, a history of familial adenomatous polyposis, hereditary non polyposis CRC. Results: A total of 1856 patients were included in the study. Of these 53.6 % were Caucasian, 26.9% African Americans, and 19.4 % were Hispanics. Mean age of these patients was 44.7 yrs (S.D 2.6) and 57.6 % were males. Adenoma detection rate (ADR) was 22.1 % in Caucasians, 16.0 % in African Americans, 23.3% in Hispanics (Table 1). On multivariate analysis while adjusting for possible confounding factors, African Americans had lower ADR as compared to Caucasians (adjusted Odds Ratio: 0.6, 95% CI: 0.4-0.8, P-value=0.001). Conclusion: The ADR across all races in the 40-49 year age group is lower than the previously recommended ADR in patients with average risk undergoing their screening colonoscopy at 50 years of age (i.e. 25%). With the advent of new guidelines from the ACS, new benchmarks for quality indicators in colonoscopy regarding ADR will be needed. The lower ADR in African Americans suggests that further studies are needed to look for factors beyond the traditional adenoma-carcinoma pathway to understand the increasing incidence of CRC in African Americans in the younger age group.478 Figure 1 No Caption available.

Exercise in African American and White Colorectal Cancer Survivors: A Mixed Methods Approach.

African-American (AA) colorectal cancer (CRC) survivors tend to be more obese and less physically active compared to white survivors. To test the feasibility of an aerobic exercise program as well as explore perceptions about supervised exercise among AA CRC survivors. A prospective supervised exercise intervention performed on a cycle ergometer 2 days/week for 12 weeks. Peak (VO2peak) and sub-maximal exercise (6MWT) along with questionnaires (SF-36, Memorial Sloan Kettering Cancer Center Bowel Function Instrument (BFI), Functional Assessment of Cancer Therapy Scale-Colorectal (FACT-C) and Fatigue (FACIT-F), Brief Symptom Inventory (BSI). A second group of survivors participated in an interview evaluating perceptions regarding exercise. Prospective case series and qualitative interview. Research university and academic medical center. African American and white colorectal cancer survivors. Quantitative: A total of 237 letters were mailed to CRC survivors (112 white, 126 AAs). From the letters, 25 white and 15 AAs expressed interest; only five white (4.5%) and four AAs (3.2%) enrolled. Two AAs and five white survivors (7/9) finished the program. There was an improvement in peak exercise (p=0.011) and quality of life (QoL) (SF-36 total, p=0.035) post-training. Qualitative: 30 CRC survivors (12 AA and 18 white) participated in qualitative interviews and selected co-morbidity, motivation and location as primary barriers to exercise. Small sample size. Recruiting CRC survivors (regardless of race) into an exercise program is challenging, however, there are exercise and QoL benefits associated with participation. Barriers to exercise are similar between AA and white CRC survivors.

Gut microbiome profiling and colorectal cancer in African Americans and Caucasian Americans.

AIMTo determine whether and to what extent the gut microbiome is involved in regulating racial disparity in colorectal cancer (CRC).METHODSAll patients were recruited and experiments were performed in accordance with the relevant guidelines and regulations by the Institutional Review Boards (IRB), committees of the John D. Dingell VAMC and Wayne State University guidelines. African American (AA) and Caucasian American (CA) patients were scheduled for an outpatient screening for colonoscopy, and no active malignancy volunteer patients were doubly consented, initially by the gastroenterologist and later by the study coordinator, for participation in the study. The gut microbial communities in colonic effluents from AAs and CAs were examined using 16sRNA profiling, and bacterial identifications were validated by performing SYBR-based Real Time PCR. For metagenomic analysis to characterize the microbial communities, multiple software/tools were used, including Metastats and R statistical software.RESULTSIt is generally accepted that the incidence and mortality of CRC is higher in AAs than in CAs. However, the reason for this disparity is not well understood. We hypothesize that the gut microbiome plays a role in regulating this disparity. Indeed, we found significant differences in species richness and diversity between AAs and CAs. Bacteroidetes was more abundant in AAs than in CAs. In particular, the pro-inflammatory bacteria Fusobacterium nucleatum and Enterobacter species were significantly higher in AAs, whereas probiotic Akkermansia muciniphila and Bifidobacterium were higher in CAs. The polyphyletic Clostridia class showed a divergent pattern, with Clostridium XI elevated in AAs, and Clostridium IV, known for its beneficial function, higher in CAs. Lastly, the AA group had decreased microbial diversity overall in comparison to the CA group. In summary, there were significant differences in pro-inflammatory bacteria and microbial diversity between AA and CA, which may help explain the CRC disparity between groups.CONCLUSIONOur current investigation, for the first time, demonstrates microbial dysbiosis between AAs and CAs, which could contribute to the racial disparity of CRC.