title: Effects of cytochrome P450 1A1 and uridine-diphosphate-glucuronosyltransferase 1A1 allelic polymorphisms on the risk of development and the prognosis of head and neck cancers.
abstract: We studied the effect of allelic polymorphisms of cytochrome P450 1A1 (CYP1A1) and uridine-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) on the risk of development of head and neck cancers and overall survival. One hundred and forty-two head and neck cancer patients (48 with laryngeal, 42 with hypopharyngeal and 52 with mesopharyngeal tumours) were included in the study. The control group (150 individuals) included volunteers without malignant tumours. There was no statistically significant difference in age, sex distribution, or smoking habits between the two groups. The participants were genotyped for the CYP1A1 isoleucine/valine (Ile/Val) polymorphism in exon 7 and for the UGT1A1 thymine-adenine-repeat polymorphism (*1 and *28 alleles) in the promoter region of the gene. The effect of the allelic variants on survival was studied using the log-rank test, whereas the χ-test and odds ratios (OR) with 95% confidence intervals (CI) were used to compare the allelic frequencies between patients and controls. Our study revealed a significant link between the occurrence of the CYP1A1 Ile/Val, Val/Val (OR: 1.72, 95% CI: 1.02-2.96, P=0.044) and UGT1A1*28 alleles (OR: 2.74, 95% CI: 1.45-5.18, P=0.002) and an increased risk of head and neck cancers. These alleles decreased the duration of survival significantly (P=0.018 and 0.006). The survival was significantly more strongly reduced when the two high-risk alleles were carried simultaneously (OR: 2.149, 95% CI: 1.111-4.157, P=0.001). Our results suggest that the use of the CYP1A1 Ile/Val and Val/Val variants and UGT1A1*28 as biomarkers can aid risk assessment while their prognostic value can aid planning of individual therapy.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Pécs University, Pécs, Hungary. istvan.szanyi@gmail.com
authors.forename: István
authors.initials: I
authors.lastname: Szanyi
authors.forename: Gábor
authors.initials: G
authors.lastname: Ráth
authors.forename: Péter
authors.initials: P
authors.lastname: Móricz
authors.forename: Krisztina
authors.initials: K
authors.lastname: Somogyvári
authors.forename: Péter
authors.initials: P
authors.lastname: Révész
authors.forename: Imre
authors.initials: I
authors.lastname: Gerlinger
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Orsós
authors.forename: István
authors.initials: I
authors.lastname: Ember
authors.forename: István
authors.initials: I
authors.lastname: Kiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000401:mortality; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate; D000099148:UGT1A1 Enzyme
chemical_list: D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C569463:CYP1A1 protein, human