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.

Aviano Cancer Centre Aviano Italy

Cancer Registry of Norway Oslo Norway

Catalan Institute of Oncology CIBERESP IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Center of Translational Genomics University of Tartu Tartu Estonia

Centre for Epidemiology and Biostatistics University of Leeds Leeds United Kingdom

Croatian National Cancer Registry Zagreb Croatia

Department of Biometry and Data Management Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

Department of Epidemiological Methods and Etiologic Research Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

Department of Family and Preventive Medicine Division of Public Health School of Medicine University of Utah Utah USA

Department of Hygiene Epidemiology and Medical Statistics University of Athens Medical School Athens Greece

Department of Medical Sciences Cancer Epidemiology Unit CeRMS and CPO Piemonte University of Turin Turin Italy

Estonian Genome Center University of Tartu Tartu Estonia

Faculty of Health Professions Athens Technological Educational Institute Athens Greece

General Hospital of Pordenone Pordenone Italy

Geneva Cancer Registry Institute of Social and Preventive Medicine Geneva Cancer Registry IMSP University of Geneva Geneva Switzerland

Glasgow Dental School College of Medical Veterinary and Life Sciences College of Medicine University of Glasgow Glasgow United Kingdom

Huntsman Cancer Institute Salt Lake City Utah USA

Institute for Statistics Faculty of Mathematics and Computer Science University of Bremen Bremen Germany

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University of Prague Prague Czech Republic

Institute of Medical Biostatistics Epidemiology and Informatics University of Mainz Mainz Germany

Institute of Molecular and Cell Biology University of Tartu Tartu Estonia

International Agency for Research on Cancer Lyon France

Laboratory of Public Health and Population Studies Department of Molecular Medicine University of Padova Padova Italy

National Heart and Lung Institute Imperial College London London United Kingdom

School of Dental Sciences University of Newcastle Newcastle United Kingdom

School of Medicine and Dentistry University of Aberdeen Aberdeen United Kingdom

School of Medicine Royal College of Surgeons in Ireland Dublin Ireland

Trinity College School of Dental Science Dublin Ireland

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$a Ahrens, Wolfgang $u 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. $7 gn_A_00002543

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$a Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE study / $c W. Ahrens, H. Pohlabeln, R. Foraita, M. Nelis, P. Lagiou, A. Lagiou, C. Bouchardy, A. Slamova, M. Schejbalova, F. Merletti, L. Richiardi, K. Kjaerheim, A. Agudo, X. Castellsague, TV. Macfarlane, GJ. Macfarlane, YC. Lee, R. Talamini, L. Barzan, C. Canova, L. Simonato, P. Thomson, PA. McKinney, AD. McMahon, A. Znaor, CM. Healy, BE. McCartan, A. Metspalu, M. Marron, M. Hashibe, DI. Conway, P. Brennan,

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$a 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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$a Pohlabeln, Hermann $u Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.

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$a Foraita, Ronja $u Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.

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$a Nelis, Mari $u Estonian Genome Center, University of Tartu, Tartu, Estonia.

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$a Lagiou, Pagona $u Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.

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$a Lagiou, Areti $u Faculty of Health Professions, Athens Technological Educational Institute, Athens, Greece.

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$a Bouchardy, Christine $u Geneva Cancer Registry, Institute of Social and Preventive Medicine, Geneva Cancer Registry, IMSP, University of Geneva, Geneva, Switzerland.

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$a Slamova, Alena $u Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University of Prague, Prague, Czech Republic.

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$a Schejbalova, Miriam $u Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University of Prague, Prague, Czech Republic.

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$a Merletti, Franco $u Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO Piemonte University of Turin, Turin, Italy.

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$a Richiardi, Lorenzo $u Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO Piemonte University of Turin, Turin, Italy.

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$a Kjaerheim, Kristina $u Cancer Registry of Norway, Oslo, Norway.

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$a Agudo, Antonio $u 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. $7 gn_A_00002293

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$a Castellsague, Xavier $u Catalan Institute of Oncology (ICO), CIBERESP, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

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$a Macfarlane, Tatiana V $u School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom.

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$a Macfarlane, Gary J $u School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom.

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$a Lee, Yuan-Chin Amy $u Department of Family and Preventive Medicine, Division of Public Health, School of Medicine, University of Utah, Utah, USA.

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$a Talamini, Renato $u Aviano Cancer Centre, Aviano, Italy.

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$a Barzan, Luigi $u General Hospital of Pordenone, Pordenone, Italy.

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$a Canova, Cristina $u 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.

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$a Simonato, Lorenzo $u Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy.

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$a Thomson, Peter $u School of Dental Sciences, University of Newcastle, Newcastle, United Kingdom.

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$a McKinney, Patricia A $u Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom.

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$a McMahon, Alex D $u Glasgow Dental School, College of Medical, Veterinary and Life Sciences, College of Medicine, University of Glasgow, Glasgow, United Kingdom.

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$a Znaor, Ariana $u Croatian National Cancer Registry, Zagreb, Croatia.

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$a Healy, Claire M $u Trinity College School of Dental Science, Dublin, Ireland.

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$a McCartan, Bernad E $u Trinity College School of Dental Science, Dublin, Ireland; School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

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$a Metspalu, Andres $u 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.

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$a Marron, Manuela $u International Agency for Research on Cancer (IARC), Lyon, France; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University of Mainz, Mainz, Germany.

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$a Hashibe, Mia $u 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.

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$a Conway, David I $u Glasgow Dental School, College of Medical, Veterinary and Life Sciences, College of Medicine, University of Glasgow, Glasgow, United Kingdom.

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