Association of Polygenic Risk Score and Bacterial Toxins at Screening Colonoscopy with Colorectal Cancer Progression: A Multicenter Case-Control Study
Alfonso Piciocchi,
Elena Angela Pia Germinario,
Koldo Garcia Etxebarria,
Silvia Rossi,
Lupe Sanchez-Mete,
Barbara Porowska,
Vittoria Stigliano,
Paolo Trentino,
Andrea Oddi,
Fabio Accarpio,
Gian Luca Grazi,
Giovanni Bruno,
Massimo Bonucci,
Massimo Giambenedetti,
Patrizia Spigaglia,
Fabrizio Barbanti,
Slawomir Owczarek,
Ida Luzzi,
Elisabetta Delibato,
Zaira Maroccia,
Lorenza Nisticò,
Carla Fiorentini,
Mauro D’Amato,
Roberta De Angelis,
Alessia Fabbri
Affiliations
Alfonso Piciocchi
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
Elena Angela Pia Germinario
Department of Cardiovascular, Endocrine-Metabolic Diseases and Ageing, Istituto Superiore di Sanità, 00161 Rome, Italy
Koldo Garcia Etxebarria
Biodonostia, Gastrointestinal Genetics Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 20014 San Sebastian, Spain
Silvia Rossi
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
Lupe Sanchez-Mete
Gastroenterology and Digestive Endoscopy IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
Barbara Porowska
Digestive Endoscopy UOC CSC03 of the Department of General Surgery, Surgical Specialities “Paride Stefanini”, Policlinic Umberto I, University of Rome ‘Sapienza’, 00161 Rome, Italy
Vittoria Stigliano
Gastroenterology and Digestive Endoscopy IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
Paolo Trentino
Digestive Endoscopy UOC CSC03 of the Department of General Surgery, Surgical Specialities “Paride Stefanini”, Policlinic Umberto I, University of Rome ‘Sapienza’, 00161 Rome, Italy
Andrea Oddi
Hepatopancreatobiliary Surgery, IRCCS Regina Elena National Cancer Institute, 00114 Rome, Italy
Fabio Accarpio
Digestive Endoscopy UOC CSC03 of the Department of General Surgery, Surgical Specialities “Paride Stefanini”, Policlinic Umberto I, University of Rome ‘Sapienza’, 00161 Rome, Italy
Gian Luca Grazi
Hepatopancreatobiliary Surgery, IRCCS Regina Elena National Cancer Institute, 00114 Rome, Italy
Giovanni Bruno
Department of Translational and Precision Medicine, Gastroenterology Unit, Policlinic Umberto I, University of Rome ‘Sapienza’, 00161 Rome, Italy
Massimo Bonucci
Associazione Ricerca Terapie Oncologiche Integrate, 00165 Rome, Italy
Massimo Giambenedetti
Department of Cardiovascular, Endocrine-Metabolic Diseases and Ageing, Istituto Superiore di Sanità, 00161 Rome, Italy
Patrizia Spigaglia
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Fabrizio Barbanti
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Slawomir Owczarek
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Ida Luzzi
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Elisabetta Delibato
Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy
Zaira Maroccia
Department of Cardiovascular, Endocrine-Metabolic Diseases and Ageing, Istituto Superiore di Sanità, 00161 Rome, Italy
Lorenza Nisticò
Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy
Carla Fiorentini
Associazione Ricerca Terapie Oncologiche Integrate, 00165 Rome, Italy
Mauro D’Amato
Gastrointestinal Genetics Lab, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Roberta De Angelis
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
Alessia Fabbri
Department of Cardiovascular, Endocrine-Metabolic Diseases and Ageing, Istituto Superiore di Sanità, 00161 Rome, Italy
Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and its incidence is correlated with infections, chronic inflammation, diet, and genetic factors. An emerging aspect is that microbial dysbiosis and chronic infections triggered by certain bacteria can be risk factors for tumor progression. Recent data suggest that certain bacterial toxins implicated in DNA attack or in proliferation, replication, and death can be risk factors for insurgence and progression of CRC. In this study, we recruited more than 300 biopsy specimens from people undergoing colonoscopy, and we analyzed to determine whether a correlation exists between the presence of bacterial genes coding for toxins possibly involved in CRC onset and progression and the different stages of CRC. We also analyzed to determine whether CRC-predisposing genetic factors could contribute to bacterial toxins response. Our results showed that CIF toxin is associated with polyps or adenomas, whereas pks+ seems to be a predisposing factor for CRC. Toxins from Escherichia coli as a whole have a higher incidence rate in adenocarcinoma patients compared to controls, whereas Bacteroides fragilis toxin does not seem to be associated with pre-cancerous nor with cancerous lesions. These results have been obtained irrespectively of the presence of CRC-risk loci.
