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Nat Genet. 2016 Dec;48(12):1544-1550. doi: 10.1038/ng.3685. Epub 2016 Oct 17.

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

Author information

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
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
4
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
5
UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA.
6
Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil.
7
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.
8
School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
9
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
10
Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.
11
Departamento de Medicina Preventiva, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
12
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
13
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
14
Department of Medical Sciences, University of Turin, Turin, Italy.
15
Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy.
16
Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, Aviano, Italy.
17
Cancer Registry of Norway, Oslo, Norway.
18
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.
19
Programa de Pós-Graduacão em Epidemiologia, Universidade Federal de Pelotas (UFPel), Pelotas, Brazil.
20
Epidemiology, International Center for Research (CIPE), A.C. Camargo Cancer Center, Sao Paulo, Brazil.
21
Centre for Oral Health Research, Newcastle University, Newcastle, UK.
22
Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
23
Deparment of Molecular Medicine, University of Padova, Padova, Italy.
24
Croatian National Institute of Public Health, Zagreb, Croatia.
25
Institut Català d'Oncologia (ICO)-IDIBELL, CIBERESP, l'Hospitalet de Llobregat, Barcelona, Spain.
26
School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.
27
NHS National Services Scotland (NSS), Edinburgh, UK.
28
Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
29
National Institute of Public Health, Bucharest, Romania.
30
Instituto de Oncología 'Angel H. Roffo', Universidad de Buenos Aires, Buenos Aires, Argentina.
31
Trinity College School of Dental Science, Dublin, Ireland.
32
Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
33
Regional Authority of Public Health, Banská Bystrica, Slovakia.
34
Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology (MCMCC), Warsaw, Poland.
35
Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, California, USA.
36
Clinical Translational Science Institute, University of California at San Francisco, San Francisco, California, USA.
37
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
38
Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brazil.
39
Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil.
40
Department of Head and Neck Surgery, Heliópolis Hospital, São Paulo, Brazil.
41
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
42
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
43
Institute of Otorhinolaryngology, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy.
44
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
45
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
46
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
47
German Institute of Human Nutrition in Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
48
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO)-IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain.
49
Department of Biomedical Data Sciences, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
50
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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.

PMID:
27749845
PMCID:
PMC5131845
DOI:
10.1038/ng.3685
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing financial interests: The authors declare no competing financial interests.

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