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Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Lesseur C 1 , Diergaarde B 2 , Olshan AF 3 , Wünsch-Filho V 4 , Ness AR 5 , Liu G 6 Show all authors , Lacko M 7 , Eluf-Neto J 8 , Franceschi S 1 , Lagiou P 9 , Macfarlane GJ 10 , Richiardi L 11 , Boccia S 12 , Polesel J 13 , Kjaerheim K 14 , Zaridze D 15 , Johansson M 1 , Menezes AM 16 , Curado MP 17 , Robinson M 18 , Ahrens W 19 , Canova C 20 , Znaor A 1 , Castellsagué X 21 , Conway DI 22 , Holcátová I 23 , Mates D 24 , Vilensky M 25 , Healy CM 26 , Szeszenia-Dąbrowska N 27 , Fabiánová E 28 , Lissowska J 29 , Grandis JR 30 , Weissler MC 31 , Tajara EH 32 , Nunes FD 33 , de Carvalho MB 34 , Thomas S 35 , Hung RJ 36 , Peters WH 37 , Herrero R 1 , Cadoni G 38 , Bueno-de-Mesquita HB 39 , Steffen A 40 , Agudo A 41 , Shangina O 15 , Xiao X 42 , Gaborieau V 1 , Chabrier A 1 , Anantharaman D 1 , Boffetta P 43 , Amos CI 42 , McKay JD 1 , Brennan P 1

Affiliations 

  • 1 International Agency for Research on Cancer (IARC/WHO), Lyon, France
  • 2 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • 3 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • 4 Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil
  • 5 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
  • 6 Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  • 7 Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
  • 8 Departamento de Medicina Preventiva, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 9 Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  • 10 School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK
  • 11 Department of Medical Sciences, University of Turin, Turin, Italy
  • 12 Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy
  • 13 Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, Aviano, Italy
  • 14 Cancer Registry of Norway, Oslo, Norway
  • 15 Department of Cancer Epidemiology and Prevention, Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Centre of the Russian Ministry of Health, Moscow, Russian Federation
  • 16 Programa de Pós-Graduacão em Epidemiologia, Universidade Federal de Pelotas (UFPel), Pelotas, Brazil
  • 17 Epidemiology, International Center for Research (CIPE), A.C. Camargo Cancer Center, Sao Paulo, Brazil
  • 18 Centre for Oral Health Research, Newcastle University, Newcastle, UK
  • 19 Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
  • 20 Deparment of Molecular Medicine, University of Padova, Padova, Italy
  • 21 Institut Català d'Oncologia (ICO)-IDIBELL, CIBERESP, l'Hospitalet de Llobregat, Barcelona, Spain
  • 22 School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
  • 23 Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
  • 24 National Institute of Public Health, Bucharest, Romania
  • 25 Instituto de Oncología 'Angel H. Roffo', Universidad de Buenos Aires, Buenos Aires, Argentina
  • 26 Trinity College School of Dental Science, Dublin, Ireland
  • 27 Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland
  • 28 Regional Authority of Public Health, Banská Bystrica, Slovakia
  • 29 Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology (MCMCC), Warsaw, Poland
  • 30 Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, California, USA
  • 31 Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • 32 Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brazil
  • 33 Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
  • 34 Department of Head and Neck Surgery, Heliópolis Hospital, São Paulo, Brazil
  • 35 School of Oral and Dental Sciences, University of Bristol, Bristol, UK
  • 36 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  • 37 Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
  • 38 Institute of Otorhinolaryngology, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy
  • 39 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 40 German Institute of Human Nutrition in Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
  • 41 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO)-IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain
  • 42 Department of Biomedical Data Sciences, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA
  • 43 Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Nat Genet, 2016 Dec;48(12):1544-1550.
PMID: 27749845 DOI: 10.1038/ng.3685

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.

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