Original Research ARTICLE

Front. Oncol., 12 July 2011 | http://dx.doi.org/10.3389/fonc.2011.00013

Sequence variants and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

Shu-Chun Chuang1,2, Antonio Agudo3, Wolfgang Ahrens4, Devasena Anantharaman5, Simone Benhamou6, Stefania Boccia7,8, Chu Chen9, David I. Conway10, Eleonora Fabianova11, Richard B. Hayes12, Claire M. Healy13, Ivana Holcatova14, Kristina Kjaerheim15, Pagona Lagiou16, Philip Lazarus17, Tatiana V. Macfarlane18, Manoj B. Mahimkar5, Dana Mates19, Keitaro Matsuo20, Franco Merletti21, Andres Metspalu22, Hal Morgenstern23,24, Joshua Muscat17, Gabriella Cadoni25, Andrew F. Olshan26, Mark Purdue27, Heribert Ramroth28, Peter Rudnai29, Stephen M. Schwartz9, Lorenzo Simonato30, Elaine M. Smith31, Erich M. Sturgis32, Neonilia Szeszenia-Dabrowska33, Renato Talamini34, Peter Thomson35, Qingyi Wei32, David Zaridze36, Zuo-Feng Zhang37, Ariana Znaor38, Paul Brennan1, Paolo Boffetta1,39,40 and Mia Hashibe1,41*
  • 1 Lifestyle and Cancer Group, International Agency for Research on Cancer, Lyon, France
  • 2 Department of Epidemiology and Biostatistics, Imperial College London, London, UK
  • 3 Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Hospitalet de Llobregat, Barcelona, Spain
  • 4 Bremen Institute for Prevention Research and Social Medicine, Bremen, Germany
  • 5 Cancer Research Institute, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Center, Mumbai, India
  • 6 Unité 794, INSERM, Paris, France
  • 7 Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy
  • 8 Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy
  • 9 Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 10 Dental School, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  • 11 Department of Occupational Health, Specialized State Health Institute, Banská Bystrica, Slovakia
  • 12 New York University School of Medicine, New York, NY, USA
  • 13 School of Dental Science, Trinity College Dublin, Dublin, Ireland
  • 14 First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University, Prague, Czech Republic
  • 15 Cancer Registry of Norway, Institute for Population-Based Cancer Research, Oslo, Norway
  • 16 Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece
  • 17 Penn State College of Medicine, Hershey, PA, USA
  • 18 School of Medicine and Dentistry, University of Aberdeen, Scotland, UK
  • 19 Occupational Health Department, Institute of Public Health, Bucharest, Romania
  • 20 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 21 Cancer Epidemiology Unit, University of Turin, Turin, Italy
  • 22 Laboratory of Gene Technology, Estonian Biocentre, Tartu, Estonia
  • 23 Department of Epidemiology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA
  • 24 Department of Environmental Health Sciences, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA
  • 25 Institute of Otorhinolaryngology, Catholic University of the Sacred Heart, Rome, Italy
  • 26 School of Public Health, University of North Carolina, Chapel Hill, NC, USA
  • 27 National Cancer Institute, Bethesda, MD, USA
  • 28 Institute of Public Health, University of Heidelberg, Heidelberg, Germany
  • 29 Fodor József National Center for Public Health, National Institute of Environmental Health, Budapest, Hungary
  • 30 Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy
  • 31 College of Public Health, University of Iowa, Iowa City, IA, USA
  • 32 University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 33 Institute of Occupational Medicine, Lodz, Poland
  • 34 Epidemiology Unit, Aviano Cancer Centre, Aviano, Italy
  • 35 Oral and Maxillofacial Surgery School of Dental Sciences, Newcastle University, Newcastle, UK
  • 36 Cancer Research Centre, Institute of Carcinogenesis, Moscow, Russia
  • 37 Department of Epidemiology, University of California Los Angeles, School of Public Health, Los Angeles, CA, USA
  • 38 Croatian National Cancer Registry, Croatian National Institute of Public Health, Zagreb, Croatia
  • 39 The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA
  • 40 International Prevention Research Institute, Lyon, France
  • 41 Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

Previous molecular epidemiological studies on head and neck cancer have examined various single nucleotide polymorphisms (SNPs), but there are very few documented associations. In the International head and neck cancer epidemiology (INHANCE) consortium, we evaluated associations between SNPs in the metabolism, cell cycle, and DNA repair pathways and the risk of head and neck cancer. We analyzed individual-level pooled data from 14 European, North American, Central American, and Asia case–control studies (5,915 head and neck cancer cases and 10,644 controls) participating in the INHANCE consortium. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for SNP effects, adjusting for age, sex, race, and country. We observed an association between head and neck cancer risk and MGMT Leu84Phe heterozygotes (OR = 0.79, 95% CI = 0.68–0.93), XRCC1 Arg194Trp homozygotes Arg/Arg (OR = 2.3, 95% CI = 1.1–4.7), ADH1B Arg48His homozygotes Arg/Arg (OR = 2.7, 95% CI = 1.9–4.0), ADH1C Ile350Val homozygotes Ile/Ile (OR = 1.2, 95% CI = 1.1–1.4), and the GSTM1 null genotype (OR = 1.1, 95% CI = 1.0–1.2). Among these results, MGMT Leu84Phe, ADH1B Arg48His, ADH1C Ile350Arg, and the GSTM1 null genotype had fairly low false positive report probabilities (<20%). We observed associations between ADH1B Arg48His, ADH1C Ile350Arg, and GSTM1 null genotype and head and neck cancer risk. No functional study currently supports the observed association for MGMT Leu84Phe, and the association with XRCC1 Arg194Trp may be a chance finding.

Keywords: SNP, head and neck cancer, INHANCE

Citation: Chuang S-C, Agudo A, Ahrens W, Anantharaman D, Benhamou S, Boccia S, Chen C, Conway DI, Fabianova E, Hayes RB, Healy CM, Holcatova I, Kjaerheim K, Lagiou P, Lazarus P, Macfarlane TV, Mahimkar MB, Mates D, Matsuo K, Merletti F, Metspalu A, Morgenstern H, Muscat J, Cadoni G, Olshan AF, Purdue M, Ramroth H, Rudnai P. Schwartz SM, Simonato L, Smith EM, Sturgis EM, Szeszenia-Dabrowska N. Talamini R, Thomson P, Wei Q, Zaridze D, Zhang Z-F, Znaor A, Brennan P, Boffetta P and Hashibe M (2011) Sequence variants and the risk of head and neck cancer: pooled analysis in the INHANCE consortium. Front. Oncol. 1:13. doi: 10.3389/fonc.2011.00013

Received: 20 March 2011; Paper pending published: 11 April 2011;
Accepted: 13 June 2011; Published online: 12 July 2011.

Edited by:

Min Dai, Cancer Institute and Hospital Chinese Academy of Medical Sciences, China

Reviewed by:

Lifang Hou, Northwestern University, USA
Frank De Vocht, The University of Manchester, UK

Copyright: © 2011 Chuang, Agudo, Ahrens, Anantharaman, Benhamou, Boccia, Chen, Conway, Fabianova, Hayes, Healy, Holcatova, Kjaerheim, Lagiou, Lazarus, Macfarlane, Mahimkar, Mates, Matsuo, Merletti, Metspalu, Morgenstern, Muscat, Cadoni, Olshan, Purdue, Ramroth, Rudnai, Schwartz, Simonato, Smith, Sturgis, Szeszenia-Dabrowska, Talamini, Thomson, Wei, Zaridze, Zhang, Znaor, Brennan, Boffetta and Hashibe. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Mia Hashibe, Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108, USA. e-mail: mia.hashibe@utah.edu