Abstract 4927: Presence of genotoxic and/or pro-inflammatory bacterial genes in stool is associated with colorectal neoplasia

Abstract

Abstract Despite increasing adherence to routine screening and advances in therapeutic strategies, CRC is the 1st and 3rd leading cause of cancer-related death in Puerto Rico and the United States (US), respectively. Currently, CRC screening is the primary means for prevention; however, 60% of CRC patients are diagnosed at more advanced, less treatable stages, which emphasize the need for novel CRC prevention and risk stratification strategies. The etiology of CRC is complex and still incompletely understood. However, environmental factors including diet, the gut microbiota, and inflammation are accepted as major contributors to colorectal carcinogenesis. It has been shown that individuals with CRC have a distinct gut microbiota, but the mechanisms by which gut bacteria exert their CRC-promoting effects remains elusive. Certain pathogenic bacterial strains carry genes encoding toxins that promote DNA damage and perpetuate inflammation, yet the association of these toxins to CRC remains poorly understood. The aim of this study was to gain insight into the association and possible mechanisms by which a subset of the gut microbiota contribute to colorectal carcinogenesis by profiling six genes encoding genotoxic and/or pro-inflammatory bacterial toxins in stool from individuals with and without colorectal neoplasia (adenoma and CRC). The association between the genes encoding toxins and CRC was examined by characterizing the toxic colonic bacterial gene profile in stool samples from healthy individuals (controls) and individuals with colorectal neoplasia (cases). Stool samples from individuals in the mainland US (n= 20) and Caribbean Hispanics (n=33) living in Puerto Rico were provided by the NCI Early Detection Research Network and the Puerto Rico Familial Colorectal Cancer Registry, respectively. Detection pks, TcPC, GelE, cnf-1, murB, and usp in stool was performed by qPCR using gene-specific primers. Associations were assessed using odds ratios. Four of the six toxic genes were detected more frequently in stool samples from individuals from the US with colorectal neoplasia (controls=10; adenoma=10). Results show borderline statistical significant associations (p=0.07) with the presence of usp and >2 genes and a higher odds of colorectal neoplasia (OR=5.44 and OR=9.33, respectively). In the cohort from our Caribbean Hispanic subjects (controls=13; adenomas=12; CRC=8), individuals with the presence GelE weres 8.6-times ore likely to have adenomas (p=.07) and individuals with ≥ 2 of the genes were 11.3-times more likely to have CRC than individuals without these genes (p=0.04). Analysis with a larger number of samples will be necessary to determine a more definite association between the presence of the toxic genes in this panel in stool and colorectal neoplasia. Additional mechanistic analysis will be required to fully understand how these bacterial toxins contribute to colorectal carcinogenesis. Citation Format: María González-Pons, Michelle Cruz-Badia, Ramon Gomez-Moreno, Abel Baerga-Ortiz, Marcia Cruz-Correa. Presence of genotoxic and/or pro-inflammatory bacterial genes in stool is associated with colorectal neoplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4927. doi:10.1158/1538-7445.AM2017-4927