CYP2E1 G1532C, NQO1 Pro187Ser, and CYP1B1 Val432Leu polymorphisms are not associated with risk of squamous cell carcinoma of the head and neck.

Tobacco use and alcohol consumption are the major risk factors for squamous cell carcinoma of the head and neck (SCCHN; ref. 1). Polymorphisms in tobacco carcinogen– and alcohol-metabolizing genes may contribute to variation in enzyme activities and, thus, influence individual susceptibility to SCCHN. Cytochrome P450 2E1 (CYP2E1) is a phase I enzyme that catalyzes metabolic activation of several compounds found in cigarette smoke, such as N-nitroso-dimethylamine, benzene, N-nitrosonornicotine (2), and ethanol (3). More than 25 polymorphisms of CYP2E1 have been identified, one of which is G1532C located upstream of the CYP2E1 transcription start site that is believed to affect CYP2E1 expression (3). Cytochrome P450 1B1 (CYP1B1) is another phase I enzyme that activates tobacco-related carcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines (4). Among the eight potential functional polymorphisms, a G-to-A substitution resulting in an amino acid change from valine to leucine at codon 432 (V432L) may alter catalytic efficiency for the 4-hydroxylation (5). NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytosolic two-electron reductase (a phase II enzyme), catalyzes reductive activation of carcinogens from cigarette smoke, such as nitrosamines and heterocyclic amines (6), and protects cells against oxidative damage from reactive oxygen species (7). Among 14 documented polymorphisms, one functional polymorphism, a C-to-T substitution at nucleotide 609 of exon 6, causes an amino acid change from proline to serine at codon 187 (P187S; ref. 8), resulting in a loss of NQO1 activity (9). Previously published association studies have led to examination of CYP2E1 , NQO1 , and CYP1B1 polymorphisms in relation to the risk of some tobacco-related carcinomas but only few relatively small studies have examined SCCHN risk. To further verify the possible roles of these polymorphisms in the etiology of SCCHN, we investigated the associations between these three functional polymorphisms and the risk of SCCHN in a large hospital-based, case-control study in a non-Hispanic White population. Materials and Methods