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Multiple ADH genes are associated with upper aerodigestive cancers


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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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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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 to Paul 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).

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