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Multiple ADH genes are associated with upper aerodigestive cancers

Nature Genetics volume 40, pages 707–709 (2008)Cite this article

Abstract

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10−10 and 10−9, respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.

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Figure 1: Odds ratio (OR) of upper aerodigestive cancer by rs1229984 (ADH1B) and rs1573496 (ADH7) genotypes.

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Acknowledgements

First and foremost we thank all participants of the CE, LA and ARCAGE studies and the staff in the collaborating centers. Subject recruitment was supported by four grants from the European Commission (IC15-CT96-0313, IC15-CT98-0322, IC18-CT97-0222 and QLK1-CT2001-00182) and one grant from the World Cancer Research Fund (WCRF 99A28). Genotyping and analysis was funded by a National Cancer Institute R01 grant (contract no. CA 092039-01A2). The funding agencies did not have any involvement in the study design, collection, analysis and interpretation of the data or in the writing of report and decision to submit the paper.

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Authors and Affiliations

  1. International Agency for Research on Cancer, Lyon, France

    Mia Hashibe, James D McKay, Maria Paula Curado, Amelie Chabrier, Rayjean J Hung, Valerie Gaborieau, Paolo Boffetta & Paul Brennan

  2. Hospital Araujo Jorge, Goiania, and Populational Cancer Register of Goiania, Brazil

    Maria Paula Curado & Jose Carlos Oliveira

  3. Escola Nacional de Suade Publica, Rio de Janeiro, Brazil

    Sergio Koifman & Rosalina Koifman

  4. Cancer Research Centre, Moscow, Russia

    David Zaridze & Oxana Shangina

  5. Universidade de Sao Paulo, Sao Paulo, Brazil

    Victor Wünsch-Filho, Jose Eluf-Neto & Jose Eduardo Levi

  6. Institute of Oncology Angel H. Roffo, University of Buenos Aires, Argentina

    Elena Matos

  7. University of Athens School of Medicine, Athens, Greece

    Pagona Lagiou & Areti Lagiou

  8. Institut National de la Santé et de la Recherche Médicale U794, Evry, France

    Simone Benhamou

  9. Geneva Cancer Registry, Geneva, Switzerland

    Christine Bouchardy

  10. Institute of Occupational Medicine, Lodz, Poland

    Neonilia Szeszenia-Dabrowska

  11. Universidade Federal de Pelotas, Pelotas, Brazil

    Ana Menezes & Marinel Mór Dall'Agnol

  12. Unit of Cancer Epidemiology, CeRMS and University of Turin, Turin, Italy

    Franco Merletti & Lorenzo Richiardi

  13. Institute of Oncology and Radiobiology, Havana, Cuba

    Leticia Fernandez & Juan Lence

  14. Aviano Cancer Centre, Aviano, Italy

    Renato Talamini

  15. General Hospital of Pordenone, Pordenone, Italy

    Luigi Barzan

  16. Institute of Public Health, Bucharest, Romania

    Dana Mates

  17. University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania

    Ioan Nicolae Mates

  18. Cancer Registry of Norway, Oslo, Norway

    Kristina Kjaerheim

  19. University of Aberdeen School of Medicine, Aberdeen, UK

    Gary J Macfarlane & Tatiana V Macfarlane

  20. University of Padua, Padova, Italy

    Lorenzo Simonato & Cristina Canova

  21. Institute of Hygiene and Epidemiology, Prague, Czech Republic

    Ivana Holcátová & Vladimir Bencko

  22. Institut Català d'Oncologia, Barcelona, Spain

    Antonio Agudo & Xavier Castellsagué

  23. University of Newcastle Dental School, Newcastle, UK

    Ray Lowry

  24. Palacky University, Olomouc, Czech Republic

    Vladimir Janout & Helena Kollarova

  25. University of Glasgow Dental School, Glasgow, Scotland

    David I Conway

  26. University of Leeds Centre for Epidemiology and Biostatistics, Leeds, UK

    Patricia A McKinney

  27. Information Services Division, NHS National Services Scotland, Edinburgh, Scotland

    Patricia A McKinney

  28. Croatian National Cancer Registry, Zagreb, Croatia

    Ariana Znaor

  29. Specialized State Health Institute, Banská Bystrica, Slovakia

    Eleonora Fabianova

  30. The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

    Jolanta Lissowska

  31. School of Public Health, University of California at Berkeley, Berkeley, 94720, California, USA

    Rayjean J Hung

Authors
  1. Mia Hashibe
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  2. James D McKay
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  3. Maria Paula Curado
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  4. Jose Carlos Oliveira
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  5. Sergio Koifman
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  6. Rosalina Koifman
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  7. David Zaridze
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  8. Oxana Shangina
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  9. Victor Wünsch-Filho
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  10. Jose Eluf-Neto
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  11. Jose Eduardo Levi
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  12. Elena Matos
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  13. Pagona Lagiou
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  15. Simone Benhamou
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  16. Christine Bouchardy
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  17. Neonilia Szeszenia-Dabrowska
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  18. Ana Menezes
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  19. Marinel Mór Dall'Agnol
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  20. Franco Merletti
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  21. Lorenzo Richiardi
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  22. Leticia Fernandez
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  23. Juan Lence
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  24. Renato Talamini
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  25. Luigi Barzan
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  26. Dana Mates
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  27. Ioan Nicolae Mates
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  29. Gary J Macfarlane
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  30. Tatiana V Macfarlane
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  31. Lorenzo Simonato
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  32. Cristina Canova
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  33. Ivana Holcátová
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  34. Antonio Agudo
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  35. Xavier Castellsagué
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  36. Ray Lowry
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  37. Vladimir Janout
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  38. Helena Kollarova
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  39. David I Conway
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  40. Patricia A McKinney
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  41. Ariana Znaor
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  42. Eleonora Fabianova
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  43. Vladimir Bencko
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  44. Jolanta Lissowska
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  45. Amelie Chabrier
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  46. Rayjean J Hung
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  47. Valerie Gaborieau
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  48. Paolo Boffetta
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  49. Paul Brennan
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Contributions

P. Boffetta, P. Brennan, M.P.C., J.C.O., S.K., R.K., V.W.-F., J.E.N., E.M., A.M., M.M.D., L.F. and J. Lence jointly designed the LA study and organized the recruitment of participants. P. Brennan, P. Boffetta, D.Z., O.S., N.S.-D., D.M., I.N.M., I.H., V.J., H.K., E.F. and J. Lissowska jointly designed the CE study and organized the recruitment of participants. P. Brennan, M.H., P.L., A.L., S.B., C.B., F.M., L.R., R.T., L.B., K.K., G.J.M., T.V.M., L.S., C.C., A.A., X.C., R.L., D.I.C., P.A.M., A.Z. and V.B. jointly designed the ARCAGE study and organized the recruitment of participants. J.D.M., M.H., A.C., R.J.H., V.G., J.E.L. and P. Brennan organized biological sample storage. J.D.M., M.H., V.G. and P. Brennan conducted SNP selection and the statistical analysis. M.H., J.D.M. and P. Brennan drafted the manuscript, and all coauthors contributed to the final draft.

Corresponding author

Correspondence to Paul Brennan.

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Supplementary Methods, Supplementary Tables 1–4 and Supplementary Figures 1 and 2 (PDF 322 kb)

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Hashibe, M., McKay, J., Curado, M. et al. Multiple ADH genes are associated with upper aerodigestive cancers. Nat Genet 40, 707–709 (2008). https://doi.org/10.1038/ng.151

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