title: Association of Streptococcus gallolyticus subspecies gallolyticus with colorectal cancer: Serological evidence.
abstract: The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large-scale seroepidemiological data for SGG antibodies and their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population-based multicase-control project (MCC-Spain). MCC-Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity-purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6 VP1 proteins served as disease-specificity controls. In the control population, antibody responses to pilus proteins were mostly weak. Antibody responses to individual pilus proteins Gallo2039 (OR: 1.58, 95% CI: 1.09-2.28), Gallo2178 (OR: 1.58, 95% CI: 1.09-2.30) and Gallo2179 (OR: 1.45, 95% CI: 1.00-2.11) were significantly associated with CRC risk. The association was stronger for positivity to two or more pilus proteins of Gallo1569, Gallo2178 and Gallo2179 (OR:1.93, 95% CI: 1.04-3.56) and for double-positivity to Gallo2178 and Gallo2179 (OR: 3.54, 95% CI: 1.49-8.44). The association between SGG infection and CRC risk was stronger among individuals younger than 65 years. For the first time we demonstrated a statistically significant association of exposure to SGG antigens and CRC in a large seroepidemiological study. These results should stimulate further studies on the role of SGG in CRC pathogenesis.
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Butt
authors.affiliation: Servicio De Microbiología, Hospital Universitario Ramón Y Cajal and Instituto Ramón Y Cajal De Investigaciones Sanitarias (IRYCIS), Madrid, Spain.|Red Española De Investigación En Patología Infecciosa (REIPI), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Romero-Hernández
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Environmental and Cancer Epidemiology Unit, National Center of Epidemiology, Instituto De Salud Carlos III, Madrid, Spain.|Oncology and Hematology Area, IIS Puerta De Hierro, Cancer Epidemiology Research Group, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Gómez
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Willhauck-Fleckenstein
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Holzinger
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Universidad De León, León, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Martin
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Cancer Epidemiology Research Programme, IDIBELL, Institut Català D'oncologica L'hospitalet De Llobregat, Barcelona, Spain.|Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: National School of Public Health, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Linares
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|IDIVAL-University of Cantabria, Santander, Spain.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Dierssen-Sotos
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Navarra Public Health Institute, Pamplona, Spain.|Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|IUOPA, Universidad De Oviedo, Asturias, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain.
authors.forename: Jone M
authors.initials: JM
authors.lastname: Altzibar
authors.affiliation: Servicio De Medicina Digestiva, Hospital Univesitario Dr. Peset, Universidad De Valencia, Valencia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moreno-Osset
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Centro De Investigación En Salud Y Medio Ambiente (CYSMA), Universidad De Huelva, Huelva, Spain.|Hospital General De Riotinto, Huelva, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Franco
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Instituto De Investigación Biosanitaria De Granada (Ibs.GRANADA), Hospitales Universitarios De Granada/Universidad De Granada, Granada, Spain.
authors.forename: Rocío Olmedo
authors.initials: RO
authors.lastname: Requena
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Huerta
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Michel
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|School of Public Health, Athens, Greece.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Environmental and Cancer Epidemiology Unit, National Center of Epidemiology, Instituto De Salud Carlos III, Madrid, Spain.|Oncology and Hematology Area, IIS Puerta De Hierro, Cancer Epidemiology Research Group, Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.affiliation: Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Boleij
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Cancer Epidemiology Research Programme, IDIBELL, Institut Català D'oncologica L'hospitalet De Llobregat, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.affiliation: Servicio De Microbiología, Hospital Universitario Ramón Y Cajal and Instituto Ramón Y Cajal De Investigaciones Sanitarias (IRYCIS), Madrid, Spain.|Red Española De Investigación En Patología Infecciosa (REIPI), Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Del Campo
authors.affiliation: Department of Laboratory Medicine, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Radboud University Centre for Oncology (RUCO), Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Harold
authors.initials: H
authors.lastname: Tjalsma
authors.affiliation: CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.|Environmental and Cancer Epidemiology Unit, National Center of Epidemiology, Instituto De Salud Carlos III, Madrid, Spain.|Oncology and Hematology Area, IIS Puerta De Hierro, Cancer Epidemiology Research Group, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Aragonés
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000097:blood; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies; D013030:Spain / Q000453:epidemiology; D013290:Streptococcal Infections / Q000453:epidemiology*; D013291:Streptococcus; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial
keywords: antibodies; case-control study; epidemiology; gastrointestinal cancer; infection; pilus protein