title: Association between head and neck cancer and microsomal epoxide hydrolase genotypes.
abstract: Tobacco-associated carcinogens are catalyzed by microsomal epoxide hydrolase (mEH). Combinations of the Y113H and H139R polymorphic EPHX1 variants have been assumed to alter the enzyme activity and thus the risk of squamous cell head and neck cancer (SCCHN). Based on in vitro data, a putative low, medium and high mEH activity has been associated with combinations of these genotypes, and the respective activity categories have been frequently used in the estimation of risks for smoking-related cancers. We investigated the SCCHN risk for EPHX1 genotypes among 280 cases and 289 controls. We could not detect main effects of the EPHX1 genotypes, but a smaller risk of the 139HR genotype in smokers (odds ratio, OR, 0.57; 95% confidence interval, CI, 0.34-0.95). We could not confirm an increase of the SCCHN risk for genotype combinations according to a putative medium and high enzyme activity (OR 1.28, 95% CI 0.84-1.96; OR 0.98, 95% CI 0.58-1.64, respectively), but a significant heterogeneity of the estimated risks for the singular genotypes within these categories among smokers ( P=0.02). Further, p53 mutations among smoking cases were less frequent in the group with a putative high enzyme activity, although insignificant due to small numbers (OR 0.54, 95% CI 0.13-2.17). This supports uncertainties in categorizing genotypes with respect to limited enzyme activity data, especially when taken from in vitro experiments.
authors.affiliation: Department of Oncology (Medizinische Universitäts-Poliklinik), University of Bonn, Wilhelmstrasse 35-37, 53111 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wenghoefer
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Peter
authors.initials: P
authors.lastname: Broede
authors.forename: Stefan
authors.initials: S
authors.lastname: Fronhoffs
authors.forename: Olfert
authors.initials: O
authors.lastname: Landt
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Josef
authors.initials: J
authors.lastname: Abel
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Bolt
authors.forename: Claus
authors.initials: C
authors.lastname: Herberhold
authors.forename: Hans
authors.initials: H
authors.lastname: Vetter
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D004851:Epoxide Hydrolases