title: Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population.
abstract: BACKGROUND
  Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case-control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition.
  
  
  METHODS
  We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics.
  
  
  RESULTS
  We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10(-4)). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10(-4)). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study.
  
  
  CONCLUSIONS
  To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that pigmentation characteristics correlated with eye color are potential mediators between PARP1 and MM protection.
authors.affiliation: Health Research Institute-INCLIVA, Valencia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Peña-Chilet
authors.forename: Maite
authors.initials: M
authors.lastname: Blanquer-Maceiras
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.forename: Conrado
authors.initials: C
authors.lastname: Martinez-Cadenas
authors.forename: Manuel
authors.initials: M
authors.lastname: Martin-Gonzalez
authors.forename: Cristina
authors.initials: C
authors.lastname: Gomez-Fernandez
authors.forename: Matias
authors.initials: M
authors.lastname: Mayor
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Aviles
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D000099218:Interferon Regulatory Factor-4; C499320:PARP1 protein, human
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