Multiple ADH genes are associated with upper aerodigestive cancers (original) (raw)

• Brief Communication
• Published: 25 May 2008
• James D McKay1,
• Maria Paula Curado1,2,
• Jose Carlos Oliveira2,
• Sergio Koifman3,
• Rosalina Koifman3,
• David Zaridze4,
• Oxana Shangina4,
• Victor Wünsch-Filho5,
• Jose Eluf-Neto5,
• Jose Eduardo Levi5,
• Elena Matos6,
• Pagona Lagiou7,
• Areti Lagiou7,
• Simone Benhamou8,
• Christine Bouchardy9,
• Neonilia Szeszenia-Dabrowska10,
• Ana Menezes11,
• Marinel Mór Dall'Agnol11,
• Franco Merletti12,
• Lorenzo Richiardi12,
• Leticia Fernandez13,
• Juan Lence13,
• Renato Talamini14,
• Luigi Barzan15,
• Dana Mates16,
• Ioan Nicolae Mates17,
• Kristina Kjaerheim18,
• Gary J Macfarlane19,
• Tatiana V Macfarlane19,
• Lorenzo Simonato20,
• Cristina Canova20,
• Ivana Holcátová21,
• Antonio Agudo22,
• Xavier Castellsagué22,
• Ray Lowry23,
• Vladimir Janout24,
• Helena Kollarova24,
• David I Conway25,
• Patricia A McKinney26,27,
• Ariana Znaor28,
• Eleonora Fabianova29,
• Vladimir Bencko21,
• Jolanta Lissowska30,
• Amelie Chabrier1,
• Rayjean J Hung1,31,
• Valerie Gaborieau1,
• Paolo Boffetta1 &
• …
• Paul Brennan1

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

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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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14. Areti 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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28. Kristina Kjaerheim
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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.

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Correspondence toPaul Brennan.

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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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• Received: 10 September 2007
• Accepted: 25 March 2008
• Published: 25 May 2008
• Issue Date: June 2008
• DOI: https://doi.org/10.1038/ng.151

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