Abstract 752: Association of gut bacterial toxins with colorectal neoplasia in Lynch syndrome patients in Puerto Rico

Abstract Lynch syndrome (LS) is an autosomal dominant condition caused by germline mutations in DNA mismatch repair pathway genes that predispose individuals to develop colorectal cancer (CRC) and other malignancies. Not all LS patients develop CRC, and age at diagnosis varies significantly, even among individuals with identical mutations. Although several prospective genetic modifiers have been reported, the contribution of environmental exposures to colorectal carcinogenesis and age of onset is unknown. The gut microbiota composition, influenced by environmental factors, may have a role in CRC development. Dysbiosis, or abnormalities in host-bacteria interactions, can lead to inflammatory bowel disorders and CRC. Certain strains of bacteria, like Escherichia coli and Enterococcus sp. , harbor pro-inflammatory/genotoxic genes that promote sustained inflammation in the host- pks, tcpc, gelE, cnf-1, usp, and murB. The association between inflammation and carcinogenesis is well established, yet the contribution of bacteria-induced inflammation and genotoxicity to CRN is not fully understood. This study aims to investigate if changes in the prevalence of the genotoxic/pro-inflammatory bacterial genes are associated with CRN in LS patients. Stool samples were collected from 32 LS subjects and 94 age/gender-matched control subjects without a history of CRC. Qualitative data regarding the six genes in these samples were assessed using RT-PCR with SYBR green. Among LS subjects, 68. 8% had two or more of the six genes in their stool samples, whereas controls only had 27. 7%. Furthermore, LS subjects had 4. 06 times the odds of having ≥2 gut bacterial toxin genes in their stool (95% CI: 1. 48-11. 12) when compared to controls after adjusting by age. The most prevalent gene in LS patients was murB, detected in 62. 5% of the individuals. The presence of gelE and murB genes was significantly higher among LS patients (p-value 0. 001 and 0. 02, respectively). Interestingly, the usp gene was absent in any LS patients. Additionally, LS subjects had 4. 52 times the odds of having the gel-E gene (95% CI: 1. 69-12. 14) compared to controls after age adjustment. Given the documented evidence about the impact of CRC on the composition of gut microbiota, we performed analysis to assess the prevalence of these genes in LS subjects without a history of CRC, as well as in control subjects. After adjusting by age, LS subjects had higher odds of having ≥2 gut bacterial toxin genes in their stool (OR= 2. 94, 95%: CI 0. 52-16. 50) than controls. This study shows that LS patients have a higher prevalence of the genotoxic/pro-inflammatory bacterial genes. However, further studies are necessary to validate these associations and provide a more comprehensive understanding of the role of gut bacterial genes in colorectal neoplasia among LS patients. Citation Format: Ingrid Montes-Rodriguez, Diego Rodriguez-Santiago, Nicole Marquez-Andino, Gabriela Montalvo-Noguera, Sophia Colon-Serrano, Luis R. Llanos, Olga Diaz-Miranda, Hilmaris Centeno-Girona, Maria Gonzalez-Pons, Marcia Cruz-Correa. Association of gut bacterial toxins with colorectal neoplasia in Lynch syndrome patients in Puerto Rico 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 (6Suppl): Abstract nr 752.