title: Association of the GSTT1 polymorphism in upper aerodigestive tract cancer with tobacco smoking.
abstract: Polymorphisms in genes encoding xenobiotic-metabolizing enzymes might explain differences in the susceptibility to upper aerodigestive tract (UADT) cancers in individuals exposed to tobacco or other carcinogens. The present study aimed to evaluate the association of polymorphisms in the glutathione S-transferase (GST) candidate genes GSTM1, GSTT1, and GSTP1 with the risk of UADT cancers. GST gene polymorphisms were determined in 116 individuals with UADT cancer and 224 healthy controls using polymerase chain reaction-based methods. The GSTT1-null polymorphism was found to be a protective factor for UADT cancer [(odds ratio (OR) = 0.5, 95% confidence interval (CI) = 0.27-0.93)], although this association was not confirmed when adjusted for gender, age, smoking, alcoholism, and self-reported skin color in the multivariate logistic regression model (OR = 0.61, 95%CI = 0.29-1.28). The combined effect of GSTT1-positive genotypes with either the GSTP1 wild-type genotype (Ile/Ile) or the GSTP1 variant genotypes (Ile/Val or Val/Val) increased the risk for UADT cancer (OR = 4.34, 95%CI = 1.06-17.78 and OR = 4.55, 95%CI = 1.12-18.42, respectively). A significant interaction was observed among moderate smokers carrying the GSTT1-positive genotype. In this population, the significant gene-gene and gene-environment interactions of GST polymorphisms may confer a substantial risk to UADT cancers.
authors.affiliation: Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia, Campus de Jequié, Jequié, BA, Brasil thiago@uesb.edu.br.
authors.forename: T M
authors.initials: TM
authors.lastname: Silva
authors.affiliation: Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.
authors.forename: C R
authors.initials: CR
authors.lastname: Marques
authors.affiliation: Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.
authors.forename: M F
authors.initials: MF
authors.lastname: Marques Filho
authors.affiliation: Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.
authors.forename: A B
authors.initials: AB
authors.lastname: Marques
authors.affiliation: Universidade Federal de Sergipe, Campus de Lagarto, Lagarto, SE, Brasil.
authors.forename: G
authors.initials: G
authors.lastname: Di Pietro
authors.affiliation: Universidade Federal do Mato Grosso, Cuiabá, MT, Brasil.
authors.forename: F
authors.initials: F
authors.lastname: Rios-Santos
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human