Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

Biostatistics group Lyon France

Cancer Registry of Norway Oslo Norway

Cancer Research Institute Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre Navi Mumbai India

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

Catalan Institute of Oncology ICO IDIBELL L'Hospitalet de Llobregat Barcelona Spain; CIBER Epidemiología y Salud Pública Madrid Spain

Centro di Riferimento Oncologico IRCSS Unit of Epidemiology and Biostatistics Aviano Italy

Croatian National Cancer Registry Croatian National Institute of Public Health Zagreb Croatia

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and Masaryk University Brno Czech Republic

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

Department of Environmental Medicine and Public Health University of Padova Padova Italy; MRC HPA Centre for Environment and Health Respiratory Epidemiology and Public Health National Heart and Lung Institute Imperial College London United Kingdom

Department of Epidemiology Institute of Occupational Medicine Lodz Poland

Department of Genetics and Pathology International Hereditary Cancer Center Pomeranian Medical University Szczecin Poland

Department of Health Promotion Division of Oral Pathology Kyushu Dental University Kitakyushu Japan

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

Department of Otolaryngology and Laryngological Oncology Pomeranian Medical University Szczecin Poland

Dept of Molecular Oncology Cancer Institute Chennai Tamil Nadu India

General Hospital of Pordenone Pordenone Italy

Genetic Cancer Susceptibility group Lyon France

Genetic Epidemiology group Human Genetics Unit Edinburgh United Kingdom

Genetic Epidemiology group Lyon France

Infections and Cancer Epidemiology group Lyon France

Institute of Carcinogenesis Cancer Research Centre Moscow Russian Federation

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

Institute of Oncology and Radiobiology Havana Cuba

Institute of Public Health Section of Hygiene Faculty of Medicine Università Cattolica del Sacro Cuore Rome Italy

International Prevention Research Institute Ecully France

Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany; Faculty of Mathematics and Computer Science University of Bremen Bremen Germany

National School of Public Health FIOCRUZ Rio de Janeiro Brazil

Palacky University Olomouc Czech Republic

Regional Authority of Public Health Banska Bystrica Slovakia

Saint Mary General and Esophageal Surgery Clinic Carol Davila University of Medicine and Pharmacy Bucharest Romania

School of Medicine and Dentistry University of Aberdeen Aberdeen United Kingdom

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

Trinity College School of Dental Science Dublin Ireland

Universidade de Sao Paulo Sao Paulo Brazil

Universidade Federal de Pelotas Pelotas Brazil

University of Glasgow Dental School Glasgow Scotland United Kingdom

University of Manchester School of Dentistry Manchester United Kingdom

University of Turin Department of Medical Sciences Unit of Cancer Epidemiology Turin Italy

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