title: Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype.
abstract: Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.
authors.affiliation: Instituto de Investigación, Sanitaria Aragón (IIS Aragón), Zaragoza, Spain. asgarcia@unizar.es
authors.forename: M Asunción
authors.initials: MA
authors.lastname: García-González
authors.forename: Enrique
authors.initials: E
authors.lastname: Quintero
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.forename: David
authors.initials: D
authors.lastname: Nicolás
authors.forename: Rafael
authors.initials: R
authors.lastname: Benito
authors.forename: Mark
authors.initials: M
authors.lastname: Strunk
authors.forename: Santos
authors.initials: S
authors.lastname: Santolaria
authors.forename: Federico
authors.initials: F
authors.lastname: Sopeña
authors.forename: María
authors.initials: M
authors.lastname: Badía
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hijona
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Pérez-Aísa
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Méndez-Sánchez
authors.forename: Concha
authors.initials: C
authors.lastname: Thomson
authors.forename: Patricia
authors.initials: P
authors.lastname: Carrera
authors.forename: Elena
authors.initials: E
authors.lastname: Piazuelo
authors.forename: Pilar
authors.initials: P
authors.lastname: Jiménez
authors.forename: Jesús
authors.initials: J
authors.lastname: Espinel
authors.forename: Rafael
authors.initials: R
authors.lastname: Campo
authors.forename: Marisa
authors.initials: M
authors.lastname: Manzano
authors.forename: Fernando
authors.initials: F
authors.lastname: Geijo
authors.forename: Maria
authors.initials: M
authors.lastname: Pellisé
authors.forename: Ferrán
authors.initials: F
authors.lastname: González-Huix
authors.forename: Jorge
authors.initials: J
authors.lastname: Espinós
authors.forename: Llusia
authors.initials: L
authors.lastname: Titó
authors.forename: Manuel
authors.initials: M
authors.lastname: Zaballa
authors.forename: Roberto
authors.initials: R
authors.lastname: Pazo
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D007527:Isoenzymes; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013030:Spain / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human