Abstract B34: Association of genotoxic and/or pro-inflammatory bacterial genes to colorectal neoplasia
Authors: Gonzalez-Pons Maria , Gómez-Moreno Ramón , Baerga-Ortiz Abel , Cruz-Correa Marcia 
Published: May 2016

Background: Despite increasing adherence to routine screening and advances in therapeutic strategies, colorectal cancer (CRC) is still the1st and 3rd leading cause of cancer death in Puerto Rico and the US, respectively. The etiology of CRC is complex; however, environmental factors including diet, the gut microbiota, and inflammation are accepted as major contributors to colorectal carcinogenesis. It has been shown that individuals suffering from CRC have a distinct gut microbiota. However, the mechanisms by which gut bacteria exert their CRC-promoting effects remains elusive. Certain pathogenic bacterial strains carry genes encoding genotoxins that promote DNA damage and pro-inflammatory factors, 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 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).

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 three groups: healthy individuals (controls), individuals with colorectal neoplasia (cases). Stool samples from individuals in the mainland US (n= 30) and Caribbean Hispanics (n=24) 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. 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. Results show borderline statistical significant associations with the presence of murB and usp and higher odds of colorectal neoplasia (OR=6.29 and OR=5.44, respectively). Individuals with the presence of ≥2 of these toxic bacterial genes in stool were 7 times more likely to have colorectal neoplasia compared to individuals with &lt;2 (OR=7.43, 95% CI =1.23 to 45.01). Although variations in the prevalence of the toxic genes were observed in Caribbean Hispanics compared to individuals in the US, the presence of toxic bacterial genes in stool were associated with CRC in both populations.

Conclusions: This is the first time TcPC, GelE, and usp have been detected in the gut microflora. 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 analysis are needed to examine the factors that contribute to the observed variations in the presence of these toxic bacterial genes between individuals from the US and Caribbean Hispanics in order to investigate if the microbiome contributes to the observed disparities in CRC.

Citation Format: Maria Gonzalez-Pons, Ramón 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 Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B34.