title: Glutathione S-transferase M1 and T1 genetic polymorphisms are not related to the risk of hepatocellular carcinoma: a study in the Spanish population.
abstract: Glutathione S-transferases constitute a superfamily of enzymes that catalyse the inactivating conjugation of endogenous and environmental substrates involved in the pathogenesis of hepatocellular carcinoma (HCC) and glutathione. Genes encoding either glutathione S-transferase Mu-1 or Theta-1 (GSTM1 and GSTT1, respectively) isoforms are polymorphic. Homozygotes for the mutated inactive alleles of each gene are devoid of any specific enzymatic activity (null genotypes). Our aim was to investigate whether individuals with null GST genotypes have a higher risk of developing HCC. A total of 184 Caucasian Spanish patients with a diagnosis of HCC and 329 healthy controls of the same ethnic origin were included. Polymorphisms in GSTM1 and GSTT1 genes were identified through multiplex polymerase chain reactions, and the dihydrofolate reductase (DHFR) gene was used as internal control. No differences were found between the frequencies of GSTM1 (47.8% versus 45.3%) and GSTT1 (28.8% versus 23.1%) null genotypes in cases and controls, respectively, nor in the proportion of carriers of two, one or no active genotypes. Gender, age at diagnosis, tobacco use, chronic infection with hepatitis B or C virus and alcohol abuse did not influence these results. In conclusion, polymorphisms in GSTM1 and GSTT1 genes are not related to the incidence of HCC in a high-risk Spanish population.
authors.affiliation: Department of Gastroenterology, Hospital Clínico San Carlos, Complutense University, Madrid, Spain. jladero.hcsc@salud.madrid.org
authors.forename: José M
authors.initials: JM
authors.lastname: Ladero
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: Paloma
authors.initials: P
authors.lastname: Ropero
authors.forename: Olga
authors.initials: O
authors.lastname: Briceño
authors.forename: Ana
authors.initials: A
authors.lastname: Villegas
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013030:Spain
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1