title: Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer.
abstract: Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case-control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455-->G), and GSTP1 (A313-->G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case-controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76-2.41 and OR = 0.75; 95% CI = 0.41-1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01-3.12 and OR = 1.99; 95% CI = 1.07-3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.
authors.affiliation: Hospital do Câncer de Londrina, Londrina, PR, Brazil.
authors.forename: João Paulo Souto
authors.initials: JP
authors.lastname: Grando
authors.forename: Hellen
authors.initials: H
authors.lastname: Kuasne
authors.forename: Roberta
authors.initials: R
authors.lastname: Losi-Guembarovski
authors.forename: Iara
authors.initials: I
authors.lastname: Sant'ana Rodrigues
authors.forename: Henrique Mitsu
authors.initials: HM
authors.lastname: Matsuda
authors.forename: Paulo Emílio
authors.initials: PE
authors.lastname: Fuganti
authors.forename: Emerson Pereira
authors.initials: EP
authors.lastname: Gregório
authors.forename: Farid Libos
authors.initials: FL
authors.lastname: Júnior
authors.forename: Rodrigo Paes
authors.initials: RP
authors.lastname: de Menezes
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: de Freitas Rodrigues
authors.forename: Ilce Mara
authors.initials: IM
authors.lastname: de Syllos Cólus
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D019363:Cytochrome P-450 CYP1A1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1