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