title: Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
abstract: We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
authors.affiliation: International Agency for Research on Cancer (IARC/WHO), Lyon, France.
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authors.lastname: Diergaarde
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA.
authors.forename: Andrew F
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authors.affiliation: Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Victor
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authors.lastname: Wünsch-Filho
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Unit in Nutrition, Diet and Lifestyle at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.|School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
authors.forename: Andrew R
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authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
authors.forename: Gary J
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authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Lorenzo
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authors.forename: Mattias
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authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle, UK.
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authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Wolfgang
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authors.affiliation: Deparment of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Cristina
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authors.affiliation: Institut Català d'Oncologia (ICO)-IDIBELL, CIBERESP, l'Hospitalet de Llobregat, Barcelona, Spain.
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authors.affiliation: School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.|NHS National Services Scotland (NSS), Edinburgh, UK.
authors.forename: David I
authors.initials: DI
authors.lastname: Conway
authors.affiliation: Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Ivana
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authors.affiliation: National Institute of Public Health, Bucharest, Romania.
authors.forename: Dana
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authors.affiliation: Instituto de Oncología 'Angel H. Roffo', Universidad de Buenos Aires, Buenos Aires, Argentina.
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authors.forename: Neonila
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authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
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authors.affiliation: Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil.
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authors.affiliation: School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
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authors.affiliation: International Agency for Research on Cancer (IARC/WHO), Lyon, France.
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authors.affiliation: Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: German Institute of Human Nutrition in Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
authors.forename: Annika
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authors.affiliation: Department of Biomedical Data Sciences, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
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authors.affiliation: International Agency for Research on Cancer (IARC/WHO), Lyon, France.
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authors.affiliation: Department of Biomedical Data Sciences, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
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authors.affiliation: International Agency for Research on Cancer (IARC/WHO), Lyon, France.
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mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006680:HLA Antigens; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D010610:Pharyngeal Neoplasms / Q000235:genetics* / Q000821:virology
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens