title: Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism.
abstract: BACKGROUND
  Glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 are multifunctional enzymes involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes.
  
  
  OBJECTIVE
  Single nucleotide polymorphisms (SNPs) in GSTP1 and copy number variants in GSTM1 and GSTT1 may be candidate low-penetrance variants with a role in susceptibility to malignant melanoma (MM).
  
  
  METHODS
  In this case-control study, 562 Spanish patients with sporadic MM and 338 cancer-free control subjects were included, and the role of polymorphisms in these GST genes was investigated. Genotypes were established by quantitative real-time polymerase chain reaction for GSTM1 and GSTT1 while TaqMan probes were used to genotype GSTP1 SNPs.
  
  
  RESULTS
  The GSTP1 polymorphism rs1695, which encodes the amino acid change p.Ile105Val, was individually associated with MM [odds ratio (OR): 1·32, 95% confidence interval (CI): 1·06-1·63]. Furthermore, individuals carrying one or two MC1R nonsynonymous changes and GSTP1 rs1695 rare allele had an increased risk of developing MM (OR: 3·34, 95% CI: 1·42-8·09 and OR: 20·42, 95% CI: 2·80-417·42, respectively).
  
  
  CONCLUSIONS
  This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.
authors.affiliation: Department of Haematology and Medical Oncology, Fundación Investigación Hospital Clínico Universitario-INCLIVA, 46010 Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.forename: M
authors.initials: M
authors.lastname: Martin-Gonzalez
authors.forename: P
authors.initials: P
authors.lastname: Lazaro
authors.forename: A
authors.initials: A
authors.lastname: Pizarro
authors.forename: A
authors.initials: A
authors.lastname: Lluch
authors.forename: G
authors.initials: G
authors.lastname: Ribas
mesh_terms: D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D005127:Eye Color / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*; D013030:Spain
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D044102:Receptor, Melanocortin, Type 1; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human