Association of the NAD(P)H:quinone oxidoreductase (NQO1) 609C->T polymorphism with lung cancer risk among male smokers.

NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase) is an enzyme involved in both the detoxification and activation of a variety of substrates (1). This obligate two-electron reductase has chemoprotective properties including reduction of quinone to hydroquinone forms (1, 2), allowing avoidance of semiquinone free radical production and subsequent oxidative damage, as well as metabolism of vitamin E, catalyzing the production of a vitamin E antioxidant metabolite, vitamin E hydroquinone (3). Conversely, NQO1 is also involved in bioactivation of procarcinogens such as nitroaromatic compounds and heterocyclic amines (1, 4). A base pair change in the NQO1 gene (NQO1*2) results in a proline to serine substitution in the encoded protein, causing the production of a variant protein with only 2% enzymatic activity of the wild-type that is quickly degraded, leaving a lack of detectable protein in those homozygous for the NQO1*2 variant (5-7). Reports on the association between this NQO1 polymorphism and lung cancer risk are mixed (8-20), although most show increased risk associated with the wildtype (9-11, 15, 16, 20) or show a null association (12, 14, 17, 19). We examined the association between the NQO1 polymorphism and lung cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study and assessed any interaction with vitamin E supplementation.