Wolfgang Ahrens1, Hermann Pohlabeln2, Ronja Foraita2, Mari Nelis3, Pagona Lagiou4, Areti Lagiou5, Christine Bouchardy6, Alena Slamova7, Miriam Schejbalova7, Franco Merletti8, Lorenzo Richiardi8, Kristina Kjaerheim9, Antonio Agudo10, Xavier Castellsague11, Tatiana V Macfarlane12, Gary J Macfarlane12, Yuan-Chin Amy Lee13, Renato Talamini14, Luigi Barzan15, Cristina Canova16, Lorenzo Simonato17, Peter Thomson18, Patricia A McKinney19, Alex D McMahon20, Ariana Znaor21, Claire M Healy22, Bernad E McCartan23, Andres Metspalu24, Manuela Marron25, Mia Hashibe26, David I Conway20, Paul Brennan27. 1. 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. 2. Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. 3. Estonian Genome Center, University of Tartu, Tartu, Estonia. 4. Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. 5. Faculty of Health Professions, Athens Technological Educational Institute, Athens, Greece. 6. Geneva Cancer Registry, Institute of Social and Preventive Medicine, Geneva Cancer Registry, IMSP, University of Geneva, Geneva, Switzerland. 7. Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University of Prague, Prague, Czech Republic. 8. Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO Piemonte University of Turin, Turin, Italy. 9. Cancer Registry of Norway, Oslo, Norway. 10. 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. 11. Catalan Institute of Oncology (ICO), CIBERESP, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. 12. School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom. 13. Department of Family and Preventive Medicine, Division of Public Health, School of Medicine, University of Utah, Utah, USA. 14. Aviano Cancer Centre, Aviano, Italy. 15. General Hospital of Pordenone, Pordenone, Italy. 16. 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. 17. Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy. 18. School of Dental Sciences, University of Newcastle, Newcastle, United Kingdom. 19. Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom. 20. Glasgow Dental School, College of Medical, Veterinary and Life Sciences, College of Medicine, University of Glasgow, Glasgow, United Kingdom. 21. Croatian National Cancer Registry, Zagreb, Croatia. 22. Trinity College School of Dental Science, Dublin, Ireland. 23. Trinity College School of Dental Science, Dublin, Ireland; School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. 24. 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. 25. International Agency for Research on Cancer (IARC), Lyon, France; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University of Mainz, Mainz, Germany. 26. 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. 27. International Agency for Research on Cancer (IARC), Lyon, France. Electronic address: brennan@iarc.fr.
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. MATERIALS AND 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.
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. MATERIALS AND 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.
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