It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

CIBER de Epidemiología y Salud Pública Madrid Spain

College of Public Health The Ohio State University Columbus OH

Department of Cancer Epidemiology and Prevention Cancer Center Maria Sklodowska Curie Institute of Oncology Warsaw Poland

Department of Cancer Epidemiology and Prevention Research Alberta Health Services Calgary Alberta Canada

Department of Clinical Sciences and Community Health Università degli Studi di Milano Milan Italy

Department of Community Medicine and Epidemiology Carmel Medical Center and Bruce Rappaport Faculty of Medicine Israel Institute of Technology and Clalit Health Services National Cancer Control Center Haifa Israel

Department of Environmental Epidemiology INSERM Villejuif U170 France

Department of Epidemiology and Biostatistics Imperial College London United Kingdom

Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY

Department of Epidemiology School of Public Health UCLA Los Angeles CA

Department of Family and Preventive Medicine School of Medicine University of Utah Salt Lake City UT

Department of Medicine Memorial Sloan Kettering Cancer Center New York NY

Department of Pharmaceutical Sciences College of Pharmacy Washington State University Spokane Washington

Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea

Department of Public Health Section for Epidemiology Aarhus University Denmark

Department of Surgery Memorial Sloan Kettering Cancer Center New York NY

Departments of Epidemiology and Environmental Health Sciences School of Public Health and Comprehensive Cancer Center University of Michigan Ann Arbor MI

Division Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Epidemiology Public Health and Primary Care Faculty of Medicine Imperial College London London United Kingdom

Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Epidemiology Unit Department of Preventive Medicine Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

German Cancer Consortium Heidelberg Germany

Harvard School of Public Health Massachusetts General Hospital Harvard Medical School Boston MA

Hellenic Health Foundation Athens Greece

Institute of Carcinogenesis Blokhin Cancer Research Center Russian Academy of Medical Sciences Moscow Russia

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

International Agency for Research on Cancer Lyon France

IUOPA University Institute of Oncology University of Oviedo and CIBERESP Spain

Karmanos Cancer Institute Wayne State University Detroit MI

Laboratory of Human Carcinogenesis Center for Cancer Research National Cancer Institute Bethesda MD

Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto Canada

Masaryk Memorial Cancer Institute Brno Czech Republic

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

National Institute of Environmental Health Budapest Hungary

National Institute of Public Health Bucharest Romania

Norris Cotton Cancer Center Geisel School of Medicine Dartmouth College Lebanon USA

Palacky University Olomouc Czech Republic

Preventive Medicine and Public Health University of Santiago de Compostela Santiago de Compostela Spain

Public Health Ontario Toronto Canada

Specialized Institute of Hygiene and Epidemiology Banská Bystrica Slovakia

The Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

The Nofer Institute of Occupational Medicine Lodz Poland

Unit of Cancer Epidemiology Piedmont Children Cancer Registry Città della Salute e della Scienza di Torino Hospital and CPO Piemonte Turin Italy

Unit of Nutrition and Cancer Cancer Epidemiology Research Program Catalan Institute of Oncology Barcelona Spain

University of Hawaii Cancer Center Honolulu Hawaii

University of Montreal Hospital Research Center and School of Public Health Montreal Canada

Weill Cornell Medical College Cornell University New York NY

World Health Organization Collaborating Center for Food and Nutrition Policies Department of Hygiene Epidemiology and Medical Statistics University of Athens Medical School Athens Greece

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