BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Boston University School of Public Health Boston MA USA

Branch of Medical Statistics Biometry and Epidemiology G A Maccacaro Department of Clinical Sciences and Community Health Università degli Studi di Milano Milano Italy

Brown University Providence Rhode Island RI USA

Cancer Epidemiology Unit Centro di Riferimento Oncologico di Aviano IRCCS Aviano Italy

Cancer Registry of Norway Oslo Norway

College of Public Health University of Iowa Iowa City IA USA

Department of Biomedical and Clinical Sciences University of Milan Milan Italy

Department of Cancer Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan

Department of Economics Business Mathematics and Statistics University of Trieste Trieste Italy

Department of Epidemiology Brown University School of Public Health Providence RI USA

Department of Epidemiology Gillings School of Global Public Health Chapel Hill NC USA

Department of Epidemiology School of Public Health University of São Paulo São Paulo Brazil

Department of Hygiene Epidemiology and Medical Statistics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Sciences University of Turin Turin Italy

Department of Otolaryngology Head and Neck Surgery Baylor College of Medicine Houston Texas USA

Department of Otorhinolaryngology School of Medicine and Surgery University of Milano Bicocca Monza Italy

Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane WA USA

Departments of Epidemiology and Environmental Health Sciences School of Public Health and Department of Urology Medical School University of Michigan Ann Arbor MI USA

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA

Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan

Division of Epidemiology New York University School Of Medicine New York NY USA

Division of Head and Neck Surgical Oncology in the Department of Otolaryngology Head and Neck Surgery at Washington University School of Medicine St Louis MO USA

Division of Public Health Department of Family and Preventive Medicine University of Utah School of Medicine and Huntsman Cancer Institute Salt Lake City UT USA

Epidemiology CIPE ACCAMARGO Sao Paulo Brazil

Escola Nacional de Saude Publica Fundacao Oswaldo Cruz Rio de Janeiro Brazil

Head and Neck Surgery School of Medicine University of São Paulo São Paulo Brazil

Hospital Moinhos de Vento Porto Alegre Brazil

INSERM UMR 1018 Centre for Research in Epidemiology and Population Health Cancer Epidemiology Genes and Environment Team Villejuif France

Institut Universitaire de Médecine Sociale et Préventive Unisanté University of Lausanne Lausanne Switzerland

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

Institute of Oncology and Radiobiology Havana Cuba

Institute of Population Health Sciences National Health Research Institutes Miaoli Taiwan

Instituto de Oncología Ángel H Roffo Universidad de Buenos Aires Buenos Aires Argentina

International Agency for Research on Cancer Lyon France

Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

Medical Informatics Center Peking University Beijing China

National Institute of Health and Medical Research INSERM U1018 Villejuif France

New York Eye and Ear Infirmary New York NY USA

Penn State College of Medicine Hershey PA USA

Program in Epidemiology Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA USA

School of Medicine Dentistry and Nursing University of Glasgow Glasgow UK

School of Medicine Medical Sciences and Nutrition University of Aberdeen Aberdeen UK

Scientific Directorate Centro di Riferimento Oncologico di Aviano IRCCS Aviano Italy

The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY USA

Thoracic Head and Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston TX USA

Trinity College School of Dental Science Dublin Ireland

UCLA School of Public Health Los Angeles CA USA

Unit of Nutrition and Cancer Catalan Institute of Oncology ICO Nutrition and Cancer Group Bellvitge Biomedical Research Institute IDIBELL L'Hospitalet de Llobregat Barcelona 08908 Spain

Universidade Federal de Pelotas Pelotas Brazil

Université de Rennes INSERM EHESP Irset UMR_S 1085 Pointe à Pitre France

University of Bremen Faculty of Mathematics and Computer Science Bremen Germany

University of Hong Kong Hong Kong China

University of Padua Padova Italy

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