title: Genetic polymorphisms in DNA repair and oxidative stress pathways associated with malignant melanoma susceptibility.
abstract: BACKGROUND
  Base excision repair (BER) and nucleotide excision repair (NER) pathways eliminate a wide variety of DNA damage, including UV photoproducts. The ability of each individual to repair DNA damage following different causes might explain at least in part the variability in cancer susceptibility. Moreover, inflammatory response to UV exposure may further contribute to skin carcinogenesis by oxidative stress mechanisms. Single nucleotide polymorphisms in genes encoding various DNA-repair enzymes and oxidative stress factors may be candidate low-penetrance variants with a role in susceptibility to different cancers, particularly in those with aetiologies linked to environmental exposure, such as malignant melanoma (MM).
  
  
  METHODS
  In this case-control study, 684 Spanish sporadic MM patients and 406 cancer-free control subjects were included and the role of 46 polymorphisms belonging to 16 BER and NER genes as well as 11 genes involved in oxidative stress processes were investigated.
  
  
  RESULTS
  One polymorphism was identified to be individually associated with MM in the Spanish population. The variant was found in the NOS1 oxidative stress gene (rs2682826; p-value=0.01). These results suggest a putative role of oxidative stress processes in the genetic predisposition to melanoma.
  
  
  CONCLUSIONS
  To the authors' knowledge, this is the largest DNA repair-related SNP study in melanoma risk conducted in the Spanish population up to now. Furthermore, it also represents a comprehensive genetic study of several oxidative stress polymorphisms tested in relation to MM susceptibility.
authors.affiliation: Department of Haematology and Medical Oncology, Fundacion Investigacion Hospital Clinico Universitario-INCLIVA, Valencia, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.forename: Maria
authors.initials: M
authors.lastname: Peña-Chilet
authors.forename: Lara P
authors.initials: LP
authors.lastname: Fernandez
authors.forename: Jose A
authors.initials: JA
authors.lastname: Aviles
authors.forename: Matias
authors.initials: M
authors.lastname: Mayor
authors.forename: Manuel
authors.initials: M
authors.lastname: Martin-Gonzalez
authors.forename: Cristina
authors.initials: C
authors.lastname: Gomez-Fernandez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Casado
authors.forename: Pablo
authors.initials: P
authors.lastname: Lazaro
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Javier
authors.initials: J
authors.lastname: Benitez
authors.forename: Rafael
authors.initials: R
authors.lastname: Lozoya
authors.forename: Enrique
authors.initials: E
authors.lastname: Boldo
authors.forename: Angel
authors.initials: A
authors.lastname: Pizarro
authors.forename: Conrado
authors.initials: C
authors.lastname: Martinez-Cadenas
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D015999:Multivariate Analysis; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D013030:Spain
chemical_list: C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I