title: Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE study.
abstract: OBJECTIVE
  We aimed to assess the association of oral health (OH), dental care (DC) and mouthwash with upper-aerodigestive tract (UADT) cancer risk, and to examine the extent that enzymes involved in the metabolism of alcohol modify the effect of mouthwash.
  
  
  METHODS
  The study included 1963 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1993 controls. Subjects were interviewed about their oral health and dental care behaviors (which were converted to scores of OH and DC respectively), as well as smoking, alcohol drinking, diet, occupations, medical conditions and socio-economic status. Blood samples were taken for genetic analyses. Mouthwash use was analyzed in relation to the presence of polymorphisms of alcohol-metabolizing genes known to be associated with UADT. Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models adjusting for multiple confounders.
  
  
  RESULTS
  Fully adjusted ORs of low versus high scores of DC and OH were 2.36[CI=1.51-3.67] and 2.22[CI=1.45-3.41], respectively, for all UADT sites combined. The OR for frequent use of mouthwash use (3 or more times/day) was 3.23[CI=1.68-6.19]. The OR for the rare variant ADH7 (coding for fast ethanol metabolism) was lower in mouthwash-users (OR=0.53[CI=0.35-0.81]) as compared to never-users (OR=0.97[CI=0.73-1.29]) indicating effect modification (pheterogeneity=0.065) while no relevant differences were observed between users and non-users for the variant alleles of ADH1B, ADH1C or ALDH2.
  
  
  CONCLUSIONS
  Poor OH and DC seem to be independent risk factors for UADT because corresponding risk estimates remain substantially elevated after detailed adjustment for multiple confounders. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be fully clarified.
authors.affiliation: Department of Epidemiological Methods and Etiologic Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany; Institute for Statistics, Faculty of Mathematics and Computer Science, University of Bremen, Bremen, Germany. Electronic address: ahrens@bips.uni-bremen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ahrens
authors.affiliation: Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pohlabeln
authors.affiliation: Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Ronja
authors.initials: R
authors.lastname: Foraita
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Mari
authors.initials: M
authors.lastname: Nelis
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.affiliation: Faculty of Health Professions, Athens Technological Educational Institute, Athens, Greece.
authors.forename: Areti
authors.initials: A
authors.lastname: Lagiou
authors.affiliation: Geneva Cancer Registry, Institute of Social and Preventive Medicine, Geneva Cancer Registry, IMSP, University of Geneva, Geneva, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Bouchardy
authors.affiliation: Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University of Prague, Prague, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Slamova
authors.affiliation: Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University of Prague, Prague, Czech Republic.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schejbalova
authors.affiliation: Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO Piemonte University of Turin, Turin, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.affiliation: Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO Piemonte University of Turin, Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Richiardi
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kjaerheim
authors.affiliation: Catalan Institute of Oncology (ICO), CIBERESP, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.affiliation: Catalan Institute of Oncology (ICO), CIBERESP, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Castellsague
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Macfarlane
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Macfarlane
authors.affiliation: Department of Family and Preventive Medicine, Division of Public Health, School of Medicine, University of Utah, Utah, USA.
authors.forename: Yuan-Chin Amy
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Aviano Cancer Centre, Aviano, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.affiliation: General Hospital of Pordenone, Pordenone, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Barzan
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom; Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Canova
authors.affiliation: Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Simonato
authors.affiliation: School of Dental Sciences, University of Newcastle, Newcastle, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomson
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: McKinney
authors.affiliation: Glasgow Dental School, College of Medical, Veterinary and Life Sciences, College of Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Alex D
authors.initials: AD
authors.lastname: McMahon
authors.affiliation: Croatian National Cancer Registry, Zagreb, Croatia.
authors.forename: Ariana
authors.initials: A
authors.lastname: Znaor
authors.affiliation: Trinity College School of Dental Science, Dublin, Ireland.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Healy
authors.affiliation: Trinity College School of Dental Science, Dublin, Ireland; School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Bernad E
authors.initials: BE
authors.lastname: McCartan
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia; Estonian Genome Center, University of Tartu, Tartu, Estonia; Center of Translational Genomics, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University of Mainz, Mainz, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Marron
authors.affiliation: Department of Family and Preventive Medicine, Division of Public Health, School of Medicine, University of Utah, Utah, USA; Huntsman Cancer Institute, Salt Lake City, Utah, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Hashibe
authors.affiliation: Glasgow Dental School, College of Medical, Veterinary and Life Sciences, College of Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Conway
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France. Electronic address: brennan@iarc.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000428:Alcohol Drinking; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology*; D005060:Europe / Q000453:epidemiology; D006258:Head and Neck Neoplasms / Q000209:etiology*; D006801:Humans; D009067:Mouthwashes; D009909:Oral Health; D009910:Oral Hygiene; D012307:Risk Factors; D012907:Smoking
chemical_list: D009067:Mouthwashes
keywords: Genetic polymorphisms; Head and neck neoplasms; Oral health; Oral hygiene