Abstract A09: Association of genotoxic and/or pro-inflammatory bacterial genes to colorectal neoplasia

Abstract

Abstract Background: Although colorectal cancer (CRC) is a potentially preventable disease, it is still one of the most common and deadliest malignancies worldwide. 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, only 40% of CRC patients are diagnosed with localized-stage disease. The fact that in 60% of CRC patients are diagnosed at more advanced, less treatable stages emphasizes the need for CRC prevention and risk stratification strategies, that other than routine screening, are still unavailable. 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 mechanisms by which a subset of the gut microbiota contribute to colorectal carcinogenesis by profiling six genes encoding genotoxic and/or proinflammatory bacterial toxins in stool from individuals with and without colorectal neoplasia (adenoma and CRC). Methods: The association between the genotoxic and/or pro-inflammatory bacterial genes 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 (http://edrn.nci.nih.gov/) and the Puerto Rico Familial Colorectal Cancer Registry (http://purificar.rcm.upr.edu/index_eng.html), 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. Results: 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 were 8.6-times more 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). Conclusions: 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: Maria Gonzalez-Pons, Ramon Gómez-Moreno, Abel Baerga-Ortiz, Marcia Cruz-Correa. Association of genotoxic and/or pro-inflammatory bacterial genes to colorectal neoplasia. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A09.