title: High-activity microsomal epoxide hydrolase genotypes and the risk of oral, pharynx, and larynx cancers.
abstract: Human microsomal epoxide hydrolase (mEH), encoded by the EPHX1 gene, is involved in the metabolism of tobacco carcinogens. We investigated the effect of exon 3 and 4 polymorphisms of the EPHX1 gene in 121 patients with cancers of the oral cavity/pharynx, 129 patients with cancer of the larynx, and 172 non-cancer controls, all Caucasian regular smokers. The potential modifying role of previously analyzed GSTM1, GSTM3, and GSTP1 genotypes was also examined. Compared with the putative low-activity genotypes, odds ratios (ORs) associated with predicted intermediate and high mEH activity genotypes were significantly increased for oropharyngeal cancers [OR = 1.8; 95% confidence interval (CI) = 1.0-3.3; and OR = 2.1; 95% CI = 1.0-4.5, respectively; P(trend) = 0.03] and laryngeal cancers (OR = 1.7; 95% CI = 1.0-3.1; and OR = 2.4; 95% CI = 1.1-5.1, respectively; P(trend) = 0.02). Moreover, a positive interaction was found between mEH activity and GSTM3 genotype for laryngeal cancer. The combined EPHX1 high activity-associated genotype and GSTM3 (AB or BB) genotype conferred a 13.1-fold risk (95% CI = 3.5-48.4) compared with the concurrent presence of the EPHX1 low activity-associated genotype and the GSTM3 AA genotype. Thus, EPHX1 polymorphisms may be one of the factors of importance in susceptibility to smoking-related cancers of the upper aerodigestive tract.
authors.affiliation: Unit of Cancer Epidemiology (Institut National de la Santé et de la Recherche Médicale U521), Institut Gustave-Roussy, Villejuif, France.
authors.forename: N
authors.initials: N
authors.lastname: Jourenkova-Mironova
authors.forename: K
authors.initials: K
authors.lastname: Mitrunen
authors.forename: C
authors.initials: C
authors.lastname: Bouchardy
authors.forename: P
authors.initials: P
authors.lastname: Dayer
authors.forename: S
authors.initials: S
authors.lastname: Benhamou
authors.forename: A
authors.initials: A
authors.lastname: Hirvonen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D010610:Pharyngeal Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics
chemical_list: D005982:Glutathione Transferase; D004851:Epoxide Hydrolases