title: CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma.
abstract: Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1, GSTT1) considered separately or in different combinations, were investigated for an association with tobacco smoke-associated squamous cell carcinoma (SCC) of the larynx. The case-control study was performed in 289 patients with laryngeal SCC and in 316 cancer-free controls; all were Caucasian males from the same region of Poland and current tobacco smokers. The DNA samples were genotyped using PCR-RFLP and multiplex PCR. The variants' frequencies in both groups were compared; odds ratios and their 95% confidence intervals were calculated by logistic regression analyses. The CYP1A1*1/*4, CYP2D6*4/*4, NAT2*4/*6A genotypes, as well as the CYP1A1*4, CYP2D6*4 and NAT2*4 alleles, were found at significantly higher frequencies in cases than in controls indicating their role as "risk-elevating" factors in laryngeal SCC. Combined genotypes, characterized by the presence of the "risk-elevating" variants at more than one locus, often occurred together with the null variant of the GSTM1 gene and homozygous XPD A/A (Lys751Gln, A35931C) genotype. Furthermore, we identified some "protective" variants, found more frequently in controls than in cases, i.e. the NAT2*6A/*6A and NAT2*5B/*6A genotypes. A distribution of "risk" or "protection" genotypes/alleles seems to be connected with age as an occurrence or risk genes was more frequent in the group of "young" cases (< or = 49 years). Accumulation of certain alleles or genotypes of the CYP1A1, NAT2, GSTM1 and XPD seems to be associated with either increased or decreased risk to develop laryngeal SCC. Therefore, polymorphisms in these genes may play a role in the laryngeal cancer etiology.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, 32 Strzeszynska, 60-479 Poznan, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Gajecka
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.forename: Renata
authors.initials: R
authors.lastname: Jaskula-Sztul
authors.forename: Maciej
authors.initials: M
authors.lastname: Kujawski
authors.forename: Witold
authors.initials: W
authors.lastname: Szyfter
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szyfter
mesh_terms: D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking
chemical_list: D001191:Arylamine N-Acetyltransferase; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1