Abstract 3526: Host genetic susceptibility to gut microbiota-driven colorectal carcinogenesis

Abstract

Introduction: Colorectal cancer (CRC) is the 1st and 2nd leading cause of cancer death in men and women in Puerto Rico and the U.S., respectively. A dynamic balance between the host immune system and the gut bacterial communities is essential to protect colonic tissues against chronic inflammation, which may lead to CRC. The main goal of this study was to investigate if SNPs in the promoter regions of the IL-1β, IL-6 and IL-10, key cytokines that regulate gut inflammation, increase the risk for colorectal adenomas by enriching a subset of the toxin-producing gut microbiota (gene-environment interaction). Methods: Using a case-control study design, associations between having pro-inflammatory SNPs and/or bacterial toxins in colonic mucosa or stool were assessed using odds ratios. TaqMan® SNP Genotyping Assays (ThermoFisher Scientific) for IL- 1β (rs1143627), IL-6 (rs1800795), and IL-10 (rs1800871) were performed according to the manufacturer’s recommendations. The presence of bacterial toxin genes (pks, TcPC, GelE, cnf-1, CDT, murB, and usp) in stool were determined using the QuantiTect SYBR Green PCR kit (QIAGEN). Results: Our preliminary analyses showed that individuals with the IL-1β pro-inflammatory genotype were 1.5-times more likely to have colorectal adenomas (n=232; p=0.1). Detection of usp or pks in stool (n=147) was positively associated with having adenomas (OR=2.95; CI 95%= 0.92-9.45 and OR=2.91; CI 95%=0.58-14.50, respectively). Conclusion: An evaluation of the association between having pro-inflammatory genotypes, the presence of bacterial toxin genes in stool, and colorectal adenomas using a larger sample size is warranted and currently underway. The integration of modifiable (e.g. gut bacterial toxins) and non-modifiable (e.g. host genetics) risk factors in a stratified model for CRC risk stratification and/or prevention may enhance current screening approaches. Citation Format: Ibis R. Vera-Urbina, Estefania Ayala, Ediel Rodriguez, Hilmaris Centeno-Girona, Leslie Casiano, Belisa Suarez, Marcia Cruz-Correa, Maria Gonzalez-Pons. Host genetic susceptibility to gut microbiota-driven colorectal carcinogenesis [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 3526.